Perguntas ....

//// i want the response to appear like this. Example:

After oocyte maturation is complete and fertilization ensues, which other intra- and extracellular systems does it collaborate or interlink with?

This voyage requires the coordinated efforts of both intracellular and extracellular systems. Here's an overview of these interconnected systems:

Intracellular Systems

● Haptista: Comprising haptophyte algae and centrohelids, the Haptista likely emerged around 600 million to 800 million years ago.
● CRuMs: As a recently proposed supergroup, the exact divergence timing for CRuMs is less well-defined. Tentative estimates suggest a divergence around 600 million to 800 million years ago.
● Orphan Taxa: The evolutionary timeline for orphan taxa remains uncertain due to the lack of clear phylogenomic placement. Some might have ancient origins similar to Hemimastigophora, while others might have emerged more recently.


/////// do not use words like likely, could, probably, but use the words:  would, it is hypothesized, would have.  here an example: Neuronal pruning and synaptogenesis are complex processes that are intimately linked to the development and functionality of the nervous system. While the exact point in the evolutionary timeline when these processes first appeared is not definitively known, it's supposed that they emerged gradually as nervous systems became more sophisticated.

1 Haptista: Comprising haptophyte algae and centrohelids, the Haptista likely emerged around 600 million to 800 million years ago.
2 CRuMs: As a recently proposed supergroup, the exact divergence timing for CRuMs is less well-defined. Tentative estimates suggest a divergence around 600 million to 800 million years ago.
3 Orphan Taxa: The evolutionary timeline for orphan taxa remains uncertain due to the lack of clear phylogenomic placement. Some might have ancient origins similar to Hemimastigophora, while others might have emerged more recently.


The evolution of nervous systems would have been a gradual process that spans millions of years, making it challenging to pinpoint precise stages in which specific mechanisms like neuronal pruning and synaptogenesis emerged.

Early Nervous System Evolution: In the earliest multicellular organisms, nerve cells (neurons) would have started to form basic networks, allowing for simple sensory and motor responses. These early networks would have lacked the complex pruning and refinement mechanisms seen in more advanced nervous systems.
Emergence of Synaptic Connections: As nervous systems would have become more complex, the formation of synaptic connections would have became more important. Synapses, the junctions between neurons, would have allowed for communication and signal transmission between nerve cells. Over time, mechanisms that promoted the strengthening or weakening of synapses would have emerged to enhance the efficiency of signal transmission.
Refinement and Pruning: As nervous systems would have continued to evolve, mechanisms of neuronal pruning probably would have developed as a way to fine-tune neural connections. This would have been driven by the need for more efficient neural circuits, as well as the optimization of limited resources in the developing organisms.
Adaptation and Plasticity: The ability to form new synapses and adapt existing ones, which is a hallmark of synaptogenesis, would have provided significant evolutionary advantages. Organisms with the ability to adjust their neural circuits based on experiences and environmental changes would have been better equipped to survive and thrive in changing conditions.


Point out, why an evolutionary set-up, step by step, is extremely unlikely, faced on the complexity, the requirements to instantiate various codes, languages, signaling, and proteins that had to be operational right from the beginning, and intermediate stages would bear no function, and would not be selected. Explain how this interdependence could and would not have evolved in a stepwise fashion, because one mechanism, language, or code system, without the other, would bear no function, and therefore, they had to be instantiated and created all at once, fully operational, from scratch. write  from the perspective of a proponent of intelligent design. Do not write: " From an intelligent design standpoint ". Just say it.Do not put enumeration numbers at the beginning of the sentences. 


irreducibility and Interdependence of the systems to instantiate and operate . explain which of the manufacturing, signaling, and regulatory codes and languages in the process of creating, developing, and operating      are irreducible, and interdependent within each other, and how one would not bear function without the other. Explain which code and languages communicate with each other, crosstalk, and what communication systems are essential to have functional normal cell operation. Explain how this interdependence could and would not have evolved in a stepwise fashion, because one mechanism, language, or code system, without the other, would bear no function, and therefore, they had to be instantiated and created all at once, fully operational, from scratch. write from the perspective of a proponent of intelligent design. Do not write: " From an intelligent design standpoint ". Just say it. Do not put enumeration numbers at the beginning of the sentences. 


Once it is instantiated and operational, what other intra and extracellular systems is it interdependent with?
Do not put enumeration numbers at the beginning of the sentences. 

/// write a syllogism, poiting to a designed set up, since these systems are based on semiotic code, languages, are interdependent, and had to emerge together, interlocked

give a short overview, describe it, and point out the importance in biological systems, and  Developmental Processes Shaping Organismal Form and Function



=========================================

////  provide me with  BBCode formatted references on the topics mentioned above. I'd like them in chronological order, in the following format: 

● McLaren, A. (2003). Primordial germ cells in the mouse. Developmental Biology, 262(1), 1-15. Link. (This seminal paper provides an overview of germ cell development in mice, a common model organism.)
●Raz, E. (2003). Primordial germ-cell development: the zebrafish perspective. Nature Reviews Genetics, 4(9), 690-700. Link. (Offers a comparative look using zebrafish, highlighting the conserved and unique mechanisms across species.)


=============================================

////  provide me with  BBCode formatted references on the topics mentioned above. I'd like them in chronological order, in the following format: 

1. McLaren, A. (2003). Primordial germ cells in the mouse. Developmental Biology, 262(1), 1-15. Link. (This seminal paper provides an overview of germ cell development in mice, a common model organism.)
1. Raz, E. (2003). Primordial germ-cell development: the zebrafish perspective. Nature Reviews Genetics, 4(9), 690-700. Link. (Offers a comparative look using zebrafish, highlighting the conserved and unique mechanisms across species.)

=============================================


take the above list, subdivide and list them in the below topics and categories, and if one category does not have a paper in the provided list, add up to 5 papers related to the category and topic to the list. do formatting exactly the same in this format:  "Please provide me with  BBCode formatted references on the topics mentioned above. I'd like them in chronological order, in the following format: standard citation format for academic papers, typically resembling the APA format.

"Please provide me with  BBCode formatted references on the topics mentioned above. I'd like them in chronological order, in the following format: standard citation format for academic papers, typically resembling the APA format.

Genetic Components
Epigenetic Components of
Signaling Pathways
Regulatory Codes
Evolution
Interdependency

1. Brown, J. R. & Doolittle, W. F. (1995). Root of the Universal Tree of Life Based on Ancient Aminoacyl-tRNA Synthetase Gene Duplications. PNAS, 92(7). Link.
2. Woese, Carl. (1998). The universal ancestor. PNAS, 95(12), 6854–6859. Link.
3. Forterre, P. (2002). The origin of DNA genomes and DNA replication proteins. Current Opinion in Microbiology, 5(5), 525-532. Link.



After oocyte maturation is complete and fertilization ensues, which other intra- and extracellular systems does it collaborate or interlink with?

This voyage requires the coordinated efforts of both intracellular and extracellular systems. Here's an overview of these interconnected systems:

Intracellular Systems

1. Haptista: Comprising haptophyte algae and centrohelids, the Haptista likely emerged around 600 million to 800 million years ago.
2.CRuMs: As a recently proposed supergroup, the exact divergence timing for CRuMs is less well-defined. Tentative estimates suggest a divergence around 600 million to 800 million years ago.
3. Orphan Taxa: The evolutionary timeline for orphan taxa remains uncertain due to the lack of clear phylogenomic placement. Some might have ancient origins similar to Hemimastigophora, while others might have emerged more recently.

Write the enzyme that performs the reaction based on the keggs database, and the metabolic pathway that the reaction belongs to. Like this, in bbcode ( exact same format, do not write the reaction, only the enzyme)  
121. R11633: Enzyme: Galactokinase, Metabolic Pathway: Galactose metabolism
122. R11636: Enzyme: Galactokinase, Metabolic Pathway: Galactose metabolism
123. R02100: Enzyme: Glyceraldehyde-3-phosphate dehydrogenase, Metabolic Pathway: Glycolysis / Gluconeogenesis


What were the main findings or results of the study?
What are the main conclusions drawn from the results?
Are there any open questions or aspects of the topic that the paper suggests need further investigation?

respond in bbcode, like this: Intracellular Systems

Haptista: Comprising haptophyte algae and centrohelids, the Haptista likely emerged around 600 million to 800 million years ago.
CRuMs: As a recently proposed supergroup, the exact divergence timing for CRuMs is less well-defined. Tentative estimates suggest a divergence around 600 million to 800 million years ago.
Orphan Taxa: The evolutionary timeline for orphan taxa remains uncertain due to the lack of clear phylogenomic placement. Some might have ancient origins similar to Hemimastigophora, while others might have emerged more recently.

// give examples of observed rapid speciation.  

Just write the text. avoid repetitive words, like tapestry.

assume a framework of 7300 years for the creation event of the earth, and biodiversity, and 5300 years ago, noahs flood ( just work from this framework, no need to mention it)  

 write from a creationism/intelligent design perspective. Write as if a proponent of it would be written, but without mentioning it, ( like: from a creationist perspective, or: from an intelligent design perspective ).

========================================================================================================================================
The Last Universal Common Ancestor (LUCA) is believed to have been a complex organism with a comprehensive genetic machinery. While the exact nature and composition of LUCA remain speculative due to the vast evolutionary time that has passed since its existence, insights from shared genetic machinery among the three domains of life (Bacteria, Archaea, and Eukaryota) provide clues about what LUCA might have had.

Based on the data from studies and the inherent necessities of a genetic system, LUCA's genetic machinery would have likely included the following:

• Compartmentalized Biochemical Reactions: Suggesting areas within the cell where specific reactions occurred in isolation.
  
• Lipid Diversity: A variety of lipids that could hint at specialization of cellular membranes or membrane-bound organelles.
  
• Presence of Symbiotic Relationships: Interactions with other entities, potentially setting the stage for the evolution of organelles like mitochondria and chloroplasts via endosymbiosis.
  

//// Rewrite the previous text from an intelligent design/creationism standpoint perspective, providing inferences that point to intelligent design, without mentioning it ( like: from an intelligent design view) just write from that perspective. write and explain that for a science book do not mention chapters etc. Using the same style and approach, like the following ( this is just an example, do not adopt anything specifically in the text, it just serves as a template for the style to adopt) precise, technical, clear, elucidating, straight to the point, exhaustive, detailed, do not use repetitive words like TAPESTRY, INTRICATE. Don't do that. Do not mention evolution as explaining the origin of anything.  use bbcode for formatting  ///////// Unique ancestor for all life:  The traditional notion of a single, unique ancestor for all life is appealing in its simplicity, yet recent scientific investigations present a more complex picture. Several studies suggest that LUCA may not have been an isolated individual, but rather a colony or community of organisms. There are compelling reasons for this hypothesis. Firstly, the sheer complexity and diversity of metabolic pathways and cellular components that we find in today's organisms are difficult to reconcile with a single ancestral origin. Many of these pathways, especially those considered "core" to life, show signs of being ancient, and their divergence would suggest the presence of multiple primordial organisms sharing and exchanging genetic information. Horizontal gene transfer (HGT), where genes are transferred between organisms rather than through descent, could play a pivotal role here. HGT is widespread among modern microorganisms, allowing them to adapt rapidly to changing environments by acquiring new capabilities from neighboring microbes. If LUCA were a consortium of interacting microbes, HGT among them could lead to a shared pool of genetic innovations and adaptations. This perspective of LUCA as a community rather than an individual brings forth new challenges in our understanding. If we accept the hypothesis of a consortium of early life forms, the immediate question arises: What was the origin of this primordial community? The genesis of such a community would necessitate an environment conducive to the simultaneous emergence and coexistence of diverse proto-life entities. Prebiotic Earth would have been a mosaic of micro-niches, each with its unique blend of chemical and physical conditions. It's plausible that different life-like entities could have emerged in various niches, eventually converging or cohabiting in spaces where conditions allowed mutual existence and interaction. The subsequent interplay between these entities, including cooperative and competitive interactions, could pave the way for the emergence of a unified, interconnected community - the hypothetical LUCA consortium. Understanding the genesis of this proposed LUCA community requires a deeper dive into the conditions of the early Earth, the mechanisms of abiogenesis, and the interplay of nascent life forms in those ancient ecosystems. It’s a challenging puzzle, but each piece we uncover brings us a step closer to deciphering the enigmatic origins of life on our planet.

==========================================================================================================================

////  provide me with  BBCode formatted reference in the following format: 

1. McLaren, A. (2003). Primordial germ cells in the mouse. Developmental Biology, 262(1), 1-15. Link. (This seminal paper provides an overview of germ cell development in mice, a common model organism.)

write in bbcode
1. vvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvdeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee
2. vvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvvdeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee


Describe LBCAs   2. Horizontal Gene Transfer:
Horizontal gene transfer played a significant role in shaping the bacterial landscape, especially during the early phases of bacterial evolution. Such gene transfers often bring about biases in microbial evolution and are pivotal in understanding the origins and early diversification of bacterial life ([3] Andam & Gogarten 2011, [5] Fournier, Andam, & Gogarten 2015).

=====================================================
        /////////write in this in bbcode as a list ( the following is just an example, do not rewrite again the same text, elucidate based on the topic to be described, beforementioned:

1. Genetic Machinery 

The Last Universal Common Ancestor (LUCA) is believed to have been a complex organism with a comprehensive genetic machinery. While the exact nature and composition of LUCA remain speculative due to the vast evolutionary time that has passed since its existence, insights from shared genetic machinery among the three domains of life (Bacteria, Archaea, and Eukaryota) provide clues about what LUCA might have had.

Based on the data from studies and the inherent necessities of a genetic system, LUCA's genetic machinery would have likely included the following:

Nucleic Acid Synthesis and Maintenance:

• DNA Polymerases: Enzymes that synthesize DNA from deoxyribonucleotides.
  
• DNA Gyrase and Topoisomerases: Enzymes that manage DNA supercoiling.
  
• DNA Ligase: Enzyme that joins breaks in the DNA backbone.
  
• Ribonucleotide Reductase: Enzyme that produces deoxyribonucleotides for DNA synthesis.
  
• DNA Helicase: Enzyme that unwinds the DNA helix during replication.
  
• Primase: Synthesizes RNA primers for DNA replication initiation.
  

Transcription (from DNA to RNA):

• RNA Polymerases: Enzymes that synthesize RNA.
  
• Transcription Factors: Proteins that regulate gene expression.
  

• Heat Shock Proteins: These proteins assist in maintaining proper protein folding under high-temperature conditions.
  
• Chaperones: Proteins that help in the folding or unfolding and the assembly or disassembly of other macromolecular structures.
  

Deep-sea Hydrothermal Vents Adaptations

• Pressure-resistant Proteins: Proteins evolved to function under the immense pressure of deep-sea environments.
  
• Sulfide-utilizing Enzymes: Enzymes capable of deriving energy from the abundant sulfides present in hydrothermal vent environments.
  
• Metal-binding Proteins: Proteins that bind and utilize metals, abundant in hydrothermal vents, for various cellular functions.
  

Thermophilic Adaptations

• Thermosome: A type of chaperonin found in archaea that assists in protein folding under extreme temperature conditions.
  
• DNA Gyrase: An enzyme that introduces negative supercoils to DNA, which can help stabilize the DNA double helix at high temperatures.
  
• Thermostable Ribosomal RNA: rRNA molecules that are adapted to remain stable and functional at elevated temperatures.
  

and describe the differences and supposed evolutionary trajectory from LUCA to LBCA in each case , write; it is hypothesized, it is claimed, supposedly, It is possible to have, it would, never it could, never write as if it happened as a fact

Cellular Structure:
There's ongoing debate regarding the cellular constitution of the LBCA. Recent studies have raised questions about its nature, debating whether it was a monoderm (single-membraned organism) ([9] Léonard et al. 2022).

Phylogenetic Considerations:
Deducing the phylogenetic history of bacteria presents a complex task. However, advancements in rooted phylogenies have provided insights into the evolutionary trajectory of early bacteria, helping discern relationships and ancestral states, placing the LBCA within a well-resolved bacterial tree of life ([1] Ciccarelli et al. 2006, [6] Coleman et al. 2021).

Evolutionary Framework:
The concept of the 'Tree of Life' when applied to bacteria becomes complicated due to the frequent horizontal gene transfers. This network-like view of bacterial evolution challenges the traditional tree paradigm, emphasizing the interconnectedness of early bacterial life ([4] Puigbò, Wolf, & Koonin 2012).

Pangenomic Insights:
Reconstructions of the LBCA from multiple pangenomes provide a window into the foundational genome of bacterial life. Such reconstructions underline the versatility and adaptability of the LBCA, suggesting a genomic wealth that set the stage for the vast bacterial diversity we observe today ([8] Hyun & Palsson 2023).



Ecological Specializations

• Terrestrial Adaptations: Early descendants of the LBCA displayed traits suited for life on land, potentially positioning the LBCA or its immediate offspring as initial colonizers of terrestrial habitats.
  

Colonization and Niche Expansion

• Pioneering Terrestrial Habitats: The presence of ancient adaptations in certain LBCA lineages suggests that this ancestor or its descendants might have played a role in the initial colonization of land, marking a pivotal shift in bacterial ecology.
  
• Ecological Significance: By transitioning to land, these organisms would have played a crucial role in shaping early terrestrial ecosystems and influencing subsequent evolutionary trajectories.
  

Environmental Adaptations

• Land Adaptability: The transition from aquatic to terrestrial habitats would have required significant physiological and metabolic adaptations, emphasizing the LBCA's versatility.
  
• Interactions with Early Terrestrial Life: As one of the potential first land colonizers, the LBCA or its descendants would have established initial interactions with other pioneering terrestrial life forms, laying the foundation for future ecological networks.
  

Significance in Earth's Evolutionary History

• Marking Ecological Transitions: The shift to terrestrial habitats represents a major evolutionary milestone, and the LBCA's potential role in this underscores its significance in Earth's biological history.
  
• Influence on Subsequent Life: By setting the stage for terrestrial life, the LBCA or its immediate descendants would have indirectly influenced the evolution and ecology of myriad terrestrial organisms that followed.
  

Differences and Evolutionary Trajectory from LUCA to LBCA:

• Ecological Shifts: While LUCA is often conceived as an aquatic organism, the LBCA, or its descendants, exhibit adaptations suggesting a transition towards terrestrial habitats.
  
• Genomic Evolution: The LBCA's genome likely underwent significant changes from LUCA, influenced by environmental pressures and horizontal gene transfers.
  
• Metabolic Diversification: While LUCA's metabolism might have been more restricted, the LBCA potentially possessed a broader metabolic network, indicating its versatility and adaptability to diverse environments.
  
• Defensive Mechanisms: Due to the increasing complexity of its environment and interactions with other organisms, the LBCA may have refined or introduced new defensive systems, like CRISPR, to combat genetic intrusions.
  
• Environmental Colonization: LBCA or its early descendants might have played a pioneering role in colonizing new and varied habitats, especially terrestrial environments, thus diverging from LUCA's probable aquatic niche.
  

outline 

write not in terms as if indeed there was that evolutionary trajectory, but what would have had to occur in this transition ( from a skeptical standpoint giving the tale, but do not write explicitly: Delving into the realm of the hypothetical, just do it.)     . Basically, a hypothetical supposition. write like this: 

Nucleotide synthesis in the early stages of life would have relied on the available substrates to produce the basic building blocks: adenine, guanine, cytosine, thymine, and uracil. These processes can be likened to a primitive metabolic pathway, systematically producing each nucleotide through essential biochemical reactions, foundational for encoding genetic information. By the time the Last Bacterial Common Ancestor (LBCA) appeared, nucleotide synthesis pathways would likely have undergone evolutionary refinements. These pathways would have become more streamlined, enhancing efficiency and specificity. Instead of a rudimentary mechanism, a more optimized system would be in place, producing nucleotides at rates suitable for bacterial growth and replication. Additionally, the LBCA would likely exhibit advanced nucleotide recycling mechanisms. Salvage pathways would be essential, converting degraded DNA or RNA back into nucleotides. Such pathways reflect an evolutionary advantage, ensuring the effective utilization of cellular resources. Instead of wastage, broken nucleic acids would be treated as valuable resources, with their components reclaimed and reused. Bacterial enzymes specific to nucleotide metabolism would play crucial roles in this process. These enzymes would likely have regulatory functions, maintaining a balance between new nucleotide synthesis (de novo synthesis) and recycling. By sensing cellular nucleotide concentrations, these enzymes would adjust metabolic pathways accordingly, ensuring optimal nucleotide availability based on cellular demands and external conditions. From the hypothesized early stages of LUCA to the evolution of LBCA, the nucleotide synthesis and recycling mechanisms represent a clear progression in metabolic complexity. LUCA's initial synthesis pathways, while foundational, would be augmented and refined in LBCA. This evolution would result in more sophisticated nucleotide metabolism, highlighting the adaptive and intricate nature of bacterial evolution in response to environmental and cellular challenges.

/////// separate the entries into: Metabolic pathway ( alphabetical order) , then list Keggs number, enzyme name, and EC number. In all cases, i want the actual EC number, and real name corrispongind to the reaction, nothing ficticious, or invented.  Example below. Do transform the entire list, not partially. ( DO NOT LIST THE REACTION, ONLY THE ENZYME NAME)

Energy Metabolism:

R00127: Adenylate kinase (EC 2.7.4.3)
R01083: Fumarase (EC 4.2.1.2)
R00200: Pyruvate kinase (EC 2.7.1.40)
R00333: NDP kinase (EC 2.7.4.6)

Biotin Biosynthesis:

R03182: Diaminopelargonic acid synthase (EC 6.3.2.26)
R03231: 7,8-Diamino-pelargonic acid aminotransferase (EC 2.6.1.-)
R10699: Lysine 6-aminotransferase (EC 2.6.1.36)

Point out, why an evolutionary set-up, step by step, is extremely unlikely, faced on the complexity, the requirements to instantiate various codes, languages, signaling, and proteins that had to be operational right from the beginning, and intermediate stages would bear no function, and would not be selected. Explain how this interdependence could and would not have evolved in a stepwise fashion, because one mechanism, language, or code system, without the other, would bear no function, and therefore, they had to be instantiated and created all at once, fully operational, from scratch. write  from the perspective of a proponent of intelligent design. Do not write: " From an intelligent design standpoint ". Just say it.Do not put enumeration numbers at the beginning of the sentences. 


irreducibility and Interdependence of the systems to instantiate and operate . explain which of the manufacturing, signaling, and regulatory codes and languages in the process of creating, developing, and operating      are irreducible, and interdependent within each other, and how one would not bear function without the other. Explain which code and languages communicate with each other, crosstalk, and what communication systems are essential to have functional normal cell operation. Explain how this interdependence could and would not have evolved in a stepwise fashion, because one mechanism, language, or code system, without the other, would bear no function, and therefore, they had to be instantiated and created all at once, fully operational, from scratch. write from the perspective of a proponent of intelligent design. Do not write: " From an intelligent design standpoint ". Just say it. Do not put enumeration numbers at the beginning of the sentences. 


Determining where one species ends and another begins is not always clear-cut. This is the "species problem" or demarcation issue. Species are defined based on the genetic differences between populations. However, determining the exact degree of genetic difference required to delineate species remains a challenge. The biological species concept gained prominence. This defines a species as a group of individuals that can interbreed and produce fertile offspring in natural conditions but cannot do so with members of other groups. This concept works well for many animals, especially sexually reproducing ones


Point out, why an evolutionary set-up, step by step, of convergence of tool use and syntax in language elicits similar patterns of brain activation within the basal gangliamodules, but in very different and distant species, where cell-cell interactions, and module interaction is very different, therefor a evolutionary setup is extremely unlikely, faced on the complexity to get the same results , and therefore, they had to be instantiated and created all at once, fully operational, from scratch. write  from the perspective of a proponent of intelligent design. Do not write: " From an intelligent design standpoint ". Just say it. Do not put enumeration numbers at the beginning of the sentences.

////  provide me with  BBCode formatted references on the topics mentioned above. I'd like them in chronological order, in the following format:

1. McLaren, A. (2003). Primordial germ cells in the mouse. Developmental Biology, 262(1), 1-15. Link. (This seminal paper provides an overview of germ cell development in mice, a common model organism.)
2. Raz, E. (2003). Primordial germ-cell development: the zebrafish perspective. Nature Reviews Genetics, 4(9), 690-700. Link. (Offers a comparative look using zebrafish, highlighting the conserved and unique mechanisms across species.)

//// answer the question(s), describe in detail, and write as narrative, as if a science paper was writing it, precise, detailed, with lots of facts, DO NOT USE REPETITIVE WORDS, LIKE TAPERSTRY, INTRICATE, what the mainstream scientific establishment claims, not as a fact, OR THAT THE NARRATIVE IS COMPELLING, PLAUSIBLE, MOST PROBABLY ETC., but a skeptical viewpoint,what is claimed, from an ID perspective ( but do not mention or write it). Outline the problems, in special unsolved and unanswered questions, and the shortcomings of a non-guided narrative by natural means. Write in in bbcode, like this ( following is just an example how to use bbcode) :

Major Supposed Differences between the LBCA and LUCA

1. Genetic Machinery of the Last Bacterial Common Ancestor (LBCA)

Transitioning our gaze from LUCA to the Last Bacterial Common Ancestor (LBCA), we begin to see evolutionary subtleties taking shape, representing an era of molecular innovation and divergence. LBCA, while descended from LUCA, would have possessed a slightly different toolkit, fine-tuned for its own unique existence in a constantly changing environment. At the heart of LBCA's machinery would have been the bacterial cell wall, a defining characteristic that separates it from its archaeal siblings. The machinery needed to synthesize peptidoglycan, the main component of this wall, would have emerged.

Nucleic Acid Synthesis and Maintenance

In the annals of Earth's ancient molecular history, LUCA, oft-pictured as a primordial beginner, instead strides forth as a maestro of DNA dynamics, its systems already a testament to eons of supposed prior refinement. Think of LUCA not as a novice pianist hitting the first tentative notes, but as a concert pianist seamlessly crafting symphonies. Its nucleic acid machinery, intricate and adept, would already be performing the dance of DNA synthesis and repair with finesse. LUCA's DNA polymerases, contrary to being rudimentary, would be akin to a composer's refined hands, effortlessly translating genetic scripts into harmonious strands of life.

Molecular Components and Evolution: Transitioning from LUCA to LBCA implies the evolution of a myriad of molecular components. DNA polymerases would have to evolve from more basic structures in LUCA to more specialized versions in LBCA, facilitating more rapid and precise DNA synthesis. Helicases would undergo a transformation, perhaps increasing in efficiency or number, to ensure that DNA replication and transcription occur seamlessly.
Integration of New and Evolving Parts: In the quantum leap from LUCA to LBCA, it's not just about the evolution of individual parts, but the harmonious integration of these parts into a more intricate system. The newly formed or evolved proteins would need to seamlessly integrate with the existing machinery. For example, if LBCA introduced novel helicases or topoisomerases, they'd need to work in tandem with the ancestral versions or replace them entirely without causing transcriptional chaos. New regulatory elements would need to establish connections with the existing genetic network, ensuring that any introduced control doesn't lead to cellular anarchy. This fine-tuning would involve complex feedback mechanisms to maintain homeostasis.
Challenges in Explaining the Transition: Accepting the transition from LUCA to LBCA solely based on unguided evolutionary mechanisms presents several challenges: The emergence of new proteins or regulatory elements poses a "chicken or the egg" conundrum. For instance, a novel regulatory element that controls a specific protein's expression

//Complete the list, according to the most recent science papers until 2021, in the following format, bbcode:

Title

Subtitle

1. Haptista: Comprising haptophyte algae and centrohelids, the Haptista likely emerged around 600 million to 800 million years ago.
2. CRuMs: As a recently proposed supergroup, the exact divergence timing for CRuMs is less well-defined. Tentative estimates suggest a divergence around 600 million to 800 million years ago.






quote papers related to the topic, in this format

replace the reaction with the enzyme name, and describe the function of the enzyme, to what pathway it belongs, and why it was probably extant in luca, do it for all entries/list, in this format: 109. Eicosanoyl-CoA Hydrolase: Eicosanoyl-CoA hydrolase indicates the metabolism of eicosanoic acid, a long-chain fatty acid. It catalyzes the hydrolysis of eicosanoyl-CoA, producing eicosanoate, which can be further metabolized for energy or used in lipid synthesis.

The presence of eicosanoyl-CoA hydrolase in LUCA suggests the early existence of pathways involved in long-chain fatty acid metabolism. LUCA would have benefitted from the ability to utilize and regulate these fatty acids for various cellular processes.

write from a creationism/intelligent design standpoint without explicitly mentioning the standpoint in the question.

Alanine, Aspartate and Glutamate Metabolism:


R00258: Alanine transaminase (EC 2.6.1.2)
R00400: Aspartate transaminase (EC 2.6.1.1)
R00369: Alanine-glyoxylate transaminase (EC 2.6.1.44)
R00396: Alanine dehydrogenase (EC 1.4.1.1)

Amino Acid Biosynthesis:

R00259: N-Acetylglutamate synthase (EC 2.3.1.1)
R07245: Acetylornithine aminotransferase (EC 2.6.1.11)
R02283: Ornithine acetyltransferase (EC 2.3.1.35)
R01602: Glucose isomerase (EC 5.3.1.5)
R00243: Glutamate dehydrogenase (NAD+) (EC 1.4.1.2)
R00248: Glutamate dehydrogenase (NADP+) (EC 1.4.1.4)
R00253: Glutamine synthetase (EC 6.3.1.2)
R01465: Aminotransferase class IV (EC 2.6.1.-)
R00751: Threonine aldolase (EC 4.1.2.48)
R00372: Alanine-glyoxylate transaminase (EC 2.6.1.44)
R03758: Aminotransferase class IV (EC 2.6.1.-)
R00945: Serine hydroxymethyltransferase (EC 2.1.2.1)
R00371: Aminotransferase class IV (EC 2.6.1.-)
R03759: NADH-dependent aminoacetone oxidoreductase (EC not well-defined)
R01163: Histidine ammonia-lyase (EC 4.3.1.3)
R03013: Imidazoleacetate aminotransferase (EC 2.6.1.31)
R00691: Prephenate dehydratase (EC 4.2.1.51)
R01373: Prephenate dehydratase (EC 4.2.1.51)
R00694: Phenylalanine transaminase (EC 2.6.1.79)
R07276: Prephenate aminotransferase (EC 2.6.1.78)
R10089: Pyridoxamine-phosphate transaminase (EC 2.6.1.54)
R03314: Delta1-pyrroline-5-carboxylate reductase (EC 1.5.1.2)
R00667: Ornithine aminotransferase (EC 2.6.1.13)
R01248: Delta1-pyrroline-5-carboxylate reductase (EC 1.5.1.2)
R03313: Glutamate 5-kinase (EC 2.7.2.11)
R01251: Delta1-pyrroline-5-carboxylate reductase (EC 1.5.1.2)
R00239: Glutamate 5-kinase (EC 2.7.2.11)
R00582: Phosphoserine phosphatase (EC 3.1.3.3)
R04173: Phosphoserine aminotransferase (EC 2.6.1.52)
R01513: D-glycerate dehydrogenase (EC 1.1.1.29)

Arginine and Proline Metabolism:

R09107: N-Acetyl-L-citrulline hydrolase (EC 3.5.1.108)
R00551: Arginase (EC 3.5.3.1)
R01954: Argininosuccinate synthase (EC 6.3.4.5)
R01398: Ornithine carbamoyltransferase (EC 2.1.3.3)
R01086: Argininosuccinate lyase (EC 4.3.2.1)
R00669: Acetylornithine deacetylase (EC 3.5.1.16)

Aspartate Metabolism:

R00578: Asparagine synthetase [glutamine-hydrolyzing] (EC 6.3.5.4)
R00483: Asparagine synthetase [glutamine-hydrolyzing] (EC 6.3.5.4)
R00482: Asparagine synthetase [glutamine-hydrolyzing] (EC 6.3.5.4)
R00355: Aspartate aminotransferase (EC 2.6.1.1)

Aspartate and Asparagine Metabolism:

R00480: Aspartate kinase (EC 2.7.2.4)
R02291: Aspartate-semialdehyde dehydrogenase (EC 1.2.1.11)
R03260: Cystathionine gamma-synthase (EC 2.5.1.48 )
R01286: Cystathionine beta-lyase (EC 4.4.1.8 )

Nitrogen Metabolism:

R00149: Carbamoyl phosphate synthase (EC 6.3.4.16)

Amino Acid Metabolism:
R01771: Homoserine kinase (EC 2.7.1.39)
R01466: Threonine synthase (EC 4.2.3.1)
R00986: Anthranilate synthase (EC 4.1.3.27)
R00985: Anthranilate synthase (EC 4.1.3.27)
R01073: Phosphoribosyl-anthranilate isomerase (EC 5.3.1.24)
R03508: Anthranilate phosphoribosyltransferase (EC 2.4.2.18)
R02722: Tryptophan synthase (EC 4.2.1.20)
R03509: Phosphoribosyl-anthranilate isomerase (EC 5.3.1.24)
Folate Biosynthesis:
R05553: 4-Amino-4-deoxychorismate synthase (EC 2.6.1.85)
R01716: 4-Amino-4-deoxychorismate synthase (EC 2.6.1.85)
R02237: Dihydropteroate synthase (EC 2.5.1.15)
R00936: Dihydrofolate reductase (EC 1.5.1.3)
R00939: Dihydrofolate reductase (EC 1.5.1.3)
Nucleotide Metabolism:
R04620: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.8 )
R04638: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.8 )
R04639: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.8 )
R05046: No enzyme, likely a non-enzymatic reaction
R03503: Hydroxymethyldihydropterin pyrophosphokinase (EC 2.7.6.3)
R03067: Dihydropteroate synthase (EC 2.5.1.15)
R11072: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.
R04621: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.
R03504: No enzyme, likely a non-enzymatic reaction
R03066: Dihydropteroate synthase (EC 2.5.1.15)
R05048: No enzyme, likely a non-enzymatic reaction
R00428: Guanosine triphosphate cyclohydrolase I (EC 3.5.4.16)
R11719: No enzyme, likely a non-enzymatic reaction
R00425: GTP cyclohydrolase I (EC 3.5.4.16)
R00617: Thiamine-phosphate pyrophosphorylase (EC 2.5.1.3)
R04509: Hydroxymethylpyrimidine phosphate kinase (EC 2.7.4.7)
R05636: 1-Deoxy-D-xylulose-5-phosphate synthase (EC 2.2.1.7)
R10712: Thiamine-phosphate synthase (EC 2.5.1.3)
R07459: Sulfur carrier protein thiocarboxylate synthase (EC 2.8.1.16)
R07460: Cysteine desulfurase (EC 2.8.1.7)
R07461: Sulfur carrier protein thiocarboxylate-disulfide interchange enzyme (EC 2.8.1.16)
R10246: Cysteine-tyrosine lyase (EC 4.1.99.7)
R10247: 2-[(2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate synthase (EC 4.1.99.20)
R09977: 2-(2-Carboxy-4-methylthiazol-5-yl)ethyl phosphate synthase (EC 4.1.99.20)
R03472: AIR synthase (EC 2.7.7.25)
R12026: NAD(P)H-dependent deaminase (EC 3.5.4.35)
R01302: Chorismate pyruvate-lyase (EC 4.1.3.40)
R11102: No enzyme, likely a non-enzymatic reaction
R10339: Dihydropteroate synthase (EC 2.5.1.15)
R03388: Methylenetetrahydromethanopterin dehydrogenase (EC 1.5.98.1)
RMAN1: No enzyme, likely a non-enzymatic reaction
RMAN2: No enzyme, likely a non-enzymatic reaction
R10802: Methylenetetrahydromethanopterin dehydrogenase (EC 1.5.98.1)



Purine Metabolism:

R03443: N-Acetyl-gamma-glutamyl-phosphate reductase (EC 1.2.1.38)
R02649: N-Acetylglutamate kinase (EC 2.7.2.8 )



Purine and Pyrimidine Metabolism:

R01135: Adenylosuccinate synthase (EC 6.3.4.4)

Energy Metabolism:

R00127: Adenylate kinase (EC 2.7.4.3)
R01083: Fumarase (EC 4.2.1.2)
R00200: Pyruvate kinase (EC 2.7.1.40)
R00333: Nucleoside-diphosphate kinase (EC 2.7.4.6)

Biotin Biosynthesis:

R03182: 7,8-Diaminononanoate synthase (EC 6.3.1.25)
R03231: 7,8-Diaminononanoate synthase (EC 6.3.1.25)
R10699: Lysine 6-aminotransferase (EC 2.6.1.36)

Fatty Acid Metabolism:

R01626: Malonyl-CoA-acyl carrier protein transacylase (EC 2.3.1.39)

Biotin Biosynthesis:

R01078: Biotin synthase (EC 2.8.1.6)

Citric Acid Cycle (TCA):

R00342: Malate dehydrogenase (EC 1.1.1.37)
R01082: Fumarase (EC 4.2.1.2)
R01900: Aconitase (EC 4.2.1.3)
R00354: Citryl-CoA lyase (EC 4.1.3.34)

CO2 Fixation:

R10092: Carbonic anhydrase (EC 4.2.1.1)

Energy Metabolism:

R00200: Pyruvate kinase (EC 2.7.1.40)
R00199: Pyruvate, phosphate dikinase (EC 2.7.9.1)
R00345: Phosphoenolpyruvate carboxykinase (EC 4.1.1.32)

Fatty Acid Biosynthesis:

R00742: Acetyl-CoA carboxylase (EC 6.4.1.2)

Folate Metabolism:

R00943: Formate--tetrahydrofolate ligase (EC 6.3.4.3)
R01655: Methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9)
R01220: Methylenetetrahydrofolate reductase (EC 1.5.1.20)
R00134: Formate dehydrogenase (EC 1.2.1.2)
R07168: Methylenetetrahydrofolate reductase (EC 1.5.1.20)

Oxaloacetate Metabolism:

R00352: ATP citrate lyase (EC 2.3.3.8 )
R01322: ATP citrate lyase (EC 2.3.3.8 )
R01325: Aconitase (EC 4.2.1.3)
R00405: Succinyl-CoA ligase [ADP-forming] (EC 6.2.1.5)

Pyruvate Metabolism:

R00344: Phosphoenolpyruvate carboxylase (EC 4.1.1.31)
R00206: Pyruvate, phosphate dikinase (EC 2.7.9.1)
R00402: Succinate dehydrogenase (EC 1.3.5.1)

Redox Reactions:

R10866: Pyruvate:ferredoxin oxidoreductase (EC 1.2.7.1)


Urea Cycle:

R01197: 2-Oxoglutarate ferredoxin oxidoreductase (EC 1.2.7.3)
R01196: Pyruvate ferredoxin oxidoreductase (EC 1.2.7.1)

Cobalamin (Vitamin B12) Biosynthesis:

R05807: Cobaltochelatase (EC 4.99.1.3)
R11580: Precorrin-3B C17-methyltransferase (EC 2.1.1.131)
R08716: Cobalamin biosynthetic protein CbiG (EC not well-defined)

Coenzyme A Biosynthesis:

R02473: Pantothenate kinase (EC 2.7.1.33)
R03018: Pantothenate kinase (EC 2.7.1.33)
R00130: Dephospho-CoA kinase (EC 2.7.1.24)

Folate Metabolism:

R01226: 5,10-Methylenetetrahydrofolate reductase (EC 1.5.1.20)
R10243: Methionine synthase (EC 2.1.1.14)

NAD and FAD Metabolism:

R05705: NADH-flavin oxidoreductase (EC 1.5.1.42)
R05706: NADPH-flavin oxidoreductase (EC 1.5.1.42)

Nitrogen Metabolism:

R07157: Carbon monoxide dehydrogenase (EC 1.2.99.2)

Pantothenate and CoA Biosynthesis:

R02472: Ketopantoate reductase (EC 1.1.1.169)
R03035: Phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36)
R04230: Phosphopantothenate-cysteine ligase (EC 6.3.2.5)
R04231: Phosphopantothenate-cysteine ligase (EC 6.3.2.5)

Riboflavin Biosynthesis:

R04148: Nicotinate-nucleotide adenylyltransferase (EC 2.7.7.18)
R04594: alpha-Ribazole phosphatase (EC 3.1.3.-)

Transaminase Reactions:

R01214_2: Branched-chain amino acid aminotransferase (EC 2.6.1.42)

Uncharacterized / Other Reactions:

R04439: Acetolactate reductase (EC 1.1.1.4)
R08214: Unknown enzyme (EC not well-defined)
R08215: Unknown enzyme (EC not well-defined)
R08217: Unknown enzyme (EC not well-defined)
R08323: Unknown enzyme (EC not well-defined)
R08328: Unknown enzyme (EC not well-defined)
R08331: Homocitrate synthase (EC 2.3.3.14)
R08332: Homocitrate synthase (EC 2.3.3.14)
R10392: Unknown enzyme (EC not well-defined)
R10393: Unknown enzyme (EC not well-defined)
R10395: Unknown enzyme (EC not well-defined)
R10396: Unknown enzyme (EC not well-defined)
R10397: Unknown enzyme (EC not well-defined)
R00489: Aspartate decarboxylase (EC 4.1.1.11)

Cobalamin (Vitamin B12) Biosynthesis:

R05218: Cob(II)yrinate a,c-diamide reductase (EC 1.3.7.17)
R05220: Adenosylcobinamide kinase (EC 2.7.1.156)
R05808: Cobalt-factor III methyltransferase (EC 2.1.1.272)
R05809: Cobalt-precorrin-4 methyltransferase (EC 2.1.1.271)
R05810: Cobalt-precorrin-5A hydrolase (EC 3.7.1.12)
R05814: Cobalt-precorrin 6A reductase (EC 1.3.1.54)
R05815: Cobalt-precorrin 6Y C15-methyltransferase (EC 2.1.1.269)
R07772: Cobalt-precorrin-5B methyltransferase (EC 2.1.1.195)
R07773: Cobalt-precorrin-6A synthase (EC 2.1.1.196)
R07774: Cobalt-precorrin-6B methylase (EC 2.1.1.197)
R07775: Cobalt-precorrin-7 (C15)-methyltransferase (EC 2.1.1.270)
R05225: Adenosylcobyrinate a,c-diamide amidohydrolase (EC 3.5.1.90)
R07302: Adenosylcobinamide-GDP ribazoletransferase (EC 2.7.8.26)
R06558: Adenosylcobinamide kinase/adenosylcobinamide phosphate guanylyltransferase (EC 2.7.1.156, 2.7.7.62)
R05221: Adenosylcobinamide kinase (EC 2.7.1.156)
R05222: Adenosylcobinamide phosphate guanylyltransferase (EC 2.7.7.62)
R05223: Cobalamin biosynthetic protein CobS (EC 2.7.7.-)

Coenzyme M Biosynthesis:

R09153: Coenzyme M synthase (EC not well-defined)

Cysteine and Methionine Metabolism:

R10305: Cystathionine gamma-synthase (EC 2.5.1.48)
R00897: Cysteine synthase (EC 2.5.1.47)
R00194: S-Adenosylhomocysteine hydrolase (EC 3.3.1.1)
R01001: Cystathionine gamma-lyase (EC 4.4.1.1)

Nucleotide Metabolism:

R00573: CTP synthase (EC 6.3.4.2)
R00571: CTP synthase (EC 6.3.4.2)

Phosphonate and Phosphinate Metabolism:

R12342: L-Serine:3-phosphohydroxy-2-aminopropylphosphonate phospho-L-aminotransferase (EC 2.6.1.115)

Sulfur Metabolism:

R05789: (2R)-3-sulfolactate sulfo-lyase (EC 4.2.1.115)
R07136: NAD+-dependent 3-sulfolactate dehydrogenase (EC 1.1.1.337)
R05774: Sulfolactate dehydrogenase (EC 4.1.1.-)
R07476: 3-sulfolactaldehyde synthase (EC 2.5.1.-)

Cysteine and Methionine Metabolism:

R01291: S-Ribosylhomocysteinase (EC 3.13.1.1)
R07274: O-Acetylserine sulfhydrylase (EC 2.5.1.47)
R00586: O-Acetylserine sulfhydrylase (EC 2.5.1.47)
R01290: Cystathionine gamma-synthase (EC 2.5.1.48)
R00177: Methionine adenosyltransferase (EC 2.5.1.6)

Nucleotide Metabolism:

R11634: Deoxyadenosine triphosphate formyltransferase (EC not well-defined)
R11633: Deoxyguanosine triphosphate formyltransferase (EC not well-defined)
R11636: Deoxycytidine triphosphate formyltransferase (EC not well-defined)
R02100: dUTP pyrophosphatase (EC 3.6.1.23)
R02325: dCTP deaminase (EC 3.5.4.13)
R02101: Thymidylate synthase (EC 2.1.1.45)
R02094: Nucleoside-triphosphatase (EC 3.6.1.15)
R02093: Thymidylate kinase (EC 2.7.4.9)
Coenzyme F420 Biosynthesis:
R09399: Coenzyme F420-0:GTP 3'-phosphotransferase (EC not well-defined)
R09400: Coenzyme F420-1:GTP 3'-phosphotransferase (EC not well-defined)
R09397: (2S)-phospholactate:GTP 2-phosphotransferase (EC 2.7.8.42)
R09398: Coenzyme F420-0:LPPG 2-phosphotransferase (EC not well-defined)
Riboflavin (Vitamin B2) Biosynthesis:
R04457: Riboflavin synthase (EC 2.5.1.9)
R00549: FMN adenylyltransferase (EC 2.7.1.26)

Other Pathways:

R12161: Riboflavin biosynthetic protein RibD (EC 2.1.1.156)
R12162: FMN adenylyltransferase (EC 2.7.7.2)
R00084: Hydroxymethylbilane synthase (EC 2.5.1.61)
R00036: Porphobilinogen synthase (EC 4.2.1.24)
R02272: 5-Aminolevulinate synthase (EC 2.3.1.37)
R11626: Cobaltochelatase (EC 4.99.1.3)
R11627: Cobaltochelatase (EC 4.99.1.3)
R11628: Coenzyme F430 biosynthetic protein FbiC (EC not well-defined)
R11629: Coenzyme F430 biosynthetic protein FbiD (EC not well-defined)
R05578: Glutamyl-tRNA reductase (EC 1.2.1.70)
R04109: Glutamyl-tRNA reductase (EC 1.2.1.70)
R03165: Uroporphyrinogen-III synthase (EC 4.2.1.75)
R03194: Precorrin-2 C20-methyltransferase (EC 2.1.1.131)
R03947: Precorrin-2 dehydrogenase (EC 1.3.1.76)
R07281: 3,4-Dihydroxy 2-butanone 4-phosphate synthase (EC 4.1.99.12)

Riboflavin Metabolism:

R00066: Riboflavin synthase (EC 2.5.1.9)
R07280: Riboflavin biosynthesis protein RibD (EC 3.1.3.104)
R03458: 6,7-dimethyl-8-ribityllumazine synthase (EC 2.5.1.78)
R03459: Riboflavin biosynthesis protein RibE (EC 3.5.4.26)

Nucleotide Metabolism:

R00161: FAD synthase (EC 2.7.7.2)
R01130: Inosine-5'-monophosphate dehydrogenase (EC 1.1.1.205)
R00330: Nucleoside-diphosphate kinase (EC 2.7.4.6)
R00430: Nucleoside-diphosphate kinase (EC 2.7.4.6)
R00332: Nucleoside-diphosphate kinase (EC 2.7.4.6)
R01230: AMP deaminase (EC 3.5.4.6)
R01231: GMP synthase [glutamine-hydrolyzing] (EC 6.3.5.2)

Glycolysis:

R00947: Phosphoglucomutase (EC 5.4.2.2)
R01788: Glucose-6-phosphatase (EC 3.1.3.9)
R01070: Aldolase (EC 4.1.2.13)
R04780: Fructose-bisphosphatase (EC 3.1.3.11)
R00341: Phosphoenolpyruvate carboxykinase (EC 4.1.1.32)
R01518: Phosphoglycerate mutase (EC 5.4.2.1)
R01015: Triose-phosphate isomerase (EC 5.3.1.1)
R00431: Phosphoenolpyruvate carboxykinase (EC 4.1.1.32)
R00658: Enolase (EC 4.2.1.11)
R00959: Phosphoglucomutase (EC 5.4.2.2)
R01512: Phosphoglycerate kinase (EC 2.7.2.3)
R01061: Glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (EC 1.2.1.12)
R01063: Glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (EC 1.2.1.12)


Histidine Metabolism:

R03457: Imidazoleglycerol-phosphate hydrolase (EC 3.13.1.5)
R04640: Phosphoribosylformimino-5-amino-1-(5-phosphoribosyl)imidazolecarboxamide isomerase (EC 5.3.1.16)
R03012: Histidinol dehydrogenase (EC 1.1.1.23)
R03243: Histidinol-phosphate aminotransferase (EC 2.6.1.9)
R04558: Histidine biosynthesis bifunctional protein (EC not well-defined)
R04591: Phosphoribosylformylglycinamidine synthase (EC 6.3.5.3)
R07404: AIR carboxylase (EC 4.1.1.21)
R04144: Phosphoribosylamine--glycine ligase (EC 6.3.4.13)
R01127: IMP cyclohydrolase (EC 3.5.4.10)
R04209: Phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21)
R04325: Phosphoribosylformylglycinamidine cyclo-ligase (EC 6.3.3.1)
R04559: Imidazoleglycerol-phosphate synthase (EC 4.1.3.15)
R06975: Phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (EC 5.3.1.16)
R07405: Aminoimidazole ribotide carboxylase (EC 4.1.1.21)
R04560: Formate-dependent phosphoribosylglycinamide formyltransferase (EC 6.3.4.13)
R04463: Phosphoribosylformylglycinamidine synthase (EC 6.3.5.3)
R04208: Phosphoribosylformylglycinamidine synthase (EC 6.3.5.3)

Threonine and Isoleucine Metabolism:

R00996: Threonine deaminase (EC 4.3.1.19)
R05070: Not well-defined (EC not well-defined)
R00994: 3-methyl-2-oxobutanoate hydroxymethyltransferase (EC 2.1.2.11)
R05069: Not well-defined (EC not well-defined)
R08648: Not well-defined (EC not well-defined)
R02199: Branched-chain-amino-acid aminotransferase (EC 2.6.1.42)
R03898: Methylmalate isomerase (EC 5.3.3.5)
R03896: Methylmalate isomerase (EC 5.3.3.5)
R05068: Not well-defined (EC not well-defined)
R01213: 3-isopropylmalate dehydratase (EC 4.2.1.33)
R04426: 3-isopropylmalate dehydrogenase (EC 1.1.1.85)
R01652: 3-isopropylmalate isomerase (EC 4.2.1.33)
R03968: 3-isopropylmalate isomerase (EC 4.2.1.33)

Miscellaneous:

R01071: PRPP synthase (EC 2.7.6.1)
R04035: Nucleoside-triphosphate diphosphatase (EC 3.6.1.9)
R04037: Phosphoribosyl-AMP cyclohydrolase (EC 3.5.4.19)
R01072: Amidophosphoribosyltransferase (EC 2.4.2.14)
R07399: Not well-defined (EC not well-defined)

Amino Acid Metabolism (General):

R00257: Glutamine-dependent NAD+ synthetase (EC 6.3.5.1)
R00189: Ammonia-dependent NAD+ synthetase (EC 6.3.1.5)
Energy Metabolism:
R00104: NAD+ kinase (EC 2.7.1.23)

Lysine Biosynthesis:

R00451: Diaminopimelate decarboxylase (EC 4.1.1.20)
R02735: Diaminopimelate epimerase (EC 5.1.1.7)
R02755: Diaminopimelate reductase (EC 1.3.1.26)

Lysine Degradation:

R01934: Homoisocitrate dehydrogenase (EC 1.1.1.87)
R01939: 2-Aminoadipate transaminase (EC 2.6.1.39)

Leucine Biosynthesis:

R01090: Branched-chain-amino-acid aminotransferase (EC 2.6.1.42)
R01088: 3-Isopropylmalate dehydrogenase (EC 1.1.1.85)
R04001: Isopropylmalate isomerase (EC 4.2.1.33)

Isoleucine Biosynthesis:

R03098: 2-Aminoadipate transaminase (EC 2.6.1.39)



Methionine Metabolism:

R00946: Methionine synthase (EC 2.1.1.13)
R01777: O-Succinylhomoserine sulfhydrylase (EC 2.5.1.47)
R01773: Homoserine dehydrogenase (EC 1.1.1.3)
R01775: Homoserine dehydrogenase (EC 1.1.1.3)
R09394: Methylthiotransferase (EC 2.8.4.4)

Lysine and Aspartate Biosynthesis:

R10147: Dihydrodipicolinate synthase (EC 4.2.1.52)
R04198: Dihydrodipicolinate reductase (EC 1.3.1.26)
R04199: Dihydrodipicolinate reductase (EC 1.3.1.26)
Nicotinate and Nicotinamide Metabolism:
R04292: Quinolinate synthase (EC 2.5.1.72)

Pyruvate Metabolism:

R00271: Citrate (pro-3S)-lyase (EC 4.1.3.6)
Diaminopimelate Metabolism:
R02733: N-Acetylornithine deacetylase (EC 3.5.1.16)
R02734: N-Succinyl-L,L-diaminopimelic acid desuccinylase (EC 3.5.1.18)

Miscellaneous:

R03444: Tartronate semialdehyde reductase (EC 1.1.1.60)
R04371: Aconitase (EC 4.2.1.3)
R04467: 2-amino-6-oxopimelate transaminase (EC 2.6.1.40)
R02315: Aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase (EC 2.3.1.47)
R04364: 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase (EC 2.3.1.117)
R04365: Dihydrodipicolinate synthase (EC 4.2.1.52)
R04336: 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-acetyltransferase (EC 2.3.1.89)
R07613: Amino-acid N-acetyltransferase (EC 2.3.1.1)
R04863: Unknown (EC not well-defined)
R04390: Unknown (EC not well-defined)
R09775: Unknown (EC not well-defined)
R09776: Unknown (EC not well-defined)
R09777: Unknown (EC not well-defined)
R09778: Unknown (EC not well-defined)
R09779: Unknown (EC not well-defined)

Nucleotide Metabolism:

R03005: NAD+ pyrophosphorylase (EC 2.4.2.19)
R03348: Nicotinate-nucleotide pyrophosphorylase [carboxylating] (EC 2.4.2.19)

Energy Metabolism:

R02035: Gluconolactonase (EC 3.1.1.17)
R02736: Glucose 6-phosphate 1-dehydrogenase (EC 1.1.1.49)
R10907: Glucose 6-phosphate dehydrogenase (EC 1.1.1.49)
R01049: Ribose-phosphate pyrophosphokinase (EC 2.7.6.1)
R01830: Transaldolase (EC 2.2.1.2)
R01528: 6-Phosphogluconate dehydrogenase (EC 1.1.1.44)
R10221: 6-Phosphogluconate dehydrogenase (EC 1.1.1.44)
R01056: Ribulose-phosphate 3-epimerase (EC 5.1.3.1)
R01827: Transaldolase (EC 2.2.1.2)
R01529: Ribulose-phosphate 3-epimerase (EC 5.1.3.1)
R02739: Glucose-6-phosphate isomerase (EC 5.3.1.9)
R01641: Transketolase (EC 2.2.1.1)
R02740: Glucose-6-phosphate isomerase (EC 5.3.1.9)
R05338: Ribulose-phosphate 3-epimerase (EC 5.1.3.1)
R09780: Ribulose-phosphate 3-epimerase (EC 5.1.3.1)



Aromatic Amino Acid Metabolism:

R03083: 3-dehydroquinate synthase (EC 4.2.3.4)
R01826: 3-deoxy-7-phosphoheptulonate synthase (EC 2.5.1.54)
R01714: Chorismate synthase (EC 4.2.3.5)
R02412: Shikimate kinase (EC 2.7.1.71)
R03460: 3-phosphoshikimate 1-carboxyvinyltransferase (EC 2.5.1.19)
R03084: 3-dehydroquinate dehydratase (EC 4.2.1.10)

Amino Acid Metabolism:

R01771: Homoserine kinase (EC 2.7.1.39)
R01466: Threonine synthase (EC 4.2.3.1)
R00986: Anthranilate synthase (EC 4.1.3.27)
R00985: Anthranilate synthase (EC 4.1.3.27)
R01073: Phosphoribosyl-anthranilate isomerase (EC 5.3.1.24)
R03508: Anthranilate phosphoribosyltransferase (EC 2.4.2.18)
R02722: Tryptophan synthase (EC 4.2.1.20)
R03509: Phosphoribosyl-anthranilate isomerase (EC 5.3.1.24)

Folate Biosynthesis:

R05553: 4-Amino-4-deoxychorismate synthase (EC 2.6.1.85)
R01716: 4-Amino-4-deoxychorismate synthase (EC 2.6.1.85)
R02237: Dihydropteroate synthase (EC 2.5.1.15)
R00936: Dihydrofolate reductase (EC 1.5.1.3)
R00939: Dihydrofolate reductase (EC 1.5.1.3)

Nucleotide Metabolism:

R04620: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.8 )
R04638: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.8 )
R04639: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.8 )
R05046: No enzyme, likely a non-enzymatic reaction
R03503: Hydroxymethyldihydropterin pyrophosphokinase (EC 2.7.6.3)
R03067: Dihydropteroate synthase (EC 2.5.1.15)
R11072: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.
R04621: Dihydroneopterin-triphosphate 3',2'-epimerase (EC 5.1.99.
R03504: No enzyme, likely a non-enzymatic reaction
R03066: Dihydropteroate synthase (EC 2.5.1.15)
R05048: No enzyme, likely a non-enzymatic reaction
R00428: Guanosine triphosphate cyclohydrolase I (EC 3.5.4.16)
R11719: No enzyme, likely a non-enzymatic reaction
R00425: GTP cyclohydrolase I (EC 3.5.4.16)
R00617: Thiamine-phosphate pyrophosphorylase (EC 2.5.1.3)
R04509: Hydroxymethylpyrimidine phosphate kinase (EC 2.7.4.7)
R05636: 1-Deoxy-D-xylulose-5-phosphate synthase (EC 2.2.1.7)
R10712: Thiamine-phosphate synthase (EC 2.5.1.3)
R07459: Sulfur carrier protein thiocarboxylate synthase (EC 2.8.1.16)
R07460: Cysteine desulfurase (EC 2.8.1.7)
R07461: Sulfur carrier protein thiocarboxylate-disulfide interchange enzyme (EC 2.8.1.16)
R10246: Cysteine-tyrosine lyase (EC 4.1.99.7)
R10247: 2-[(2R,5Z)-2-Carboxy-4-methylthiazol-5(2H)-ylidene]ethyl phosphate synthase (EC 4.1.99.20)
R09977: 2-(2-Carboxy-4-methylthiazol-5-yl)ethyl phosphate synthase (EC 4.1.99.20)
R03472: AIR synthase (EC 2.7.7.25)
R12026: NAD(P)H-dependent deaminase (EC 3.5.4.35)
R01302: Chorismate pyruvate-lyase (EC 4.1.3.40)
R11102: No enzyme, likely a non-enzymatic reaction
R10339: Dihydropteroate synthase (EC 2.5.1.15)
R03388: Methylenetetrahydromethanopterin dehydrogenase (EC 1.5.98.1)
RMAN1: No enzyme, likely a non-enzymatic reaction
RMAN2: No enzyme, likely a non-enzymatic reaction
R10802: Methylenetetrahydromethanopterin dehydrogenase (EC 1.5.98.1)

Amino Acid Metabolism:

R00733: Tyrosine aminotransferase (EC 2.6.1.5)
R00732: Tyrosine dehydrogenase (EC 1.4.1.14)
R01730: Prephenate dehydrogenase (EC 1.3.1.12)
R01728: Prephenate dehydrogenase (NAD+) (EC 1.3.1.13)
R00734: 4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27)
R01715: Chorismate mutase (EC 5.4.99.5)
R01731: Aspartate aminotransferase (EC 2.6.1.1)
R01214_1: Branched-chain-amino-acid aminotransferase (EC 2.6.1.42)
R00736: Tyrosine decarboxylase (EC 4.1.1.25)

Nitrogen Metabolism:

R00575: Carbamoyl-phosphate synthase (EC 6.3.5.5)
R01397: Aspartate carbamoyltransferase (EC 2.1.3.2)
R01993: Dihydroorotase (EC 3.5.2.3)

Pyrimidine Metabolism:

R01867: Dihydroorotate dehydrogenase (EC 1.3.5.2)
R01870: Orotate phosphoribosyltransferase (EC 2.4.2.10)
R01869: Dihydroorotate dehydrogenase (EC 1.3.1.14)
R00965: Orotidine-5'-phosphate decarboxylase (EC 4.1.1.23)
R00156: Nucleoside-diphosphate kinase (EC 2.7.4.6)
R00158: UMP kinase (EC 2.7.4.14)

Valine, Leucine and Isoleucine Biosynthesis:

R04441: Methylmalonate-semialdehyde dehydrogenase (EC 1.2.1.27)
R00226: Acetolactate synthase (EC 2.2.1.6)
R05071: Acetolactate decarboxylase (EC 4.1.1.5)
R04440: Acetohydroxy-acid reductoisomerase (EC 1.1.1.86)

Energy Metabolism:

R01195: Ferredoxin-NADP+ reductase (EC 1.18.1.2)
R00315: Acetate kinase (EC 2.7.2.1)
R00230: Phosphate acetyltransferase (EC 2.3.1.8 )
R00019: Hydrogenase (EC 1.12.1.2)

Other Pathways:

R10935: No enzyme, likely a non-enzymatic reaction
R11038: No enzyme, likely a non-enzymatic reaction
R11039: No enzyme, likely a non-enzymatic reaction
R10902: Gamma-glutamyltransferase (EC 2.3.2.2)
R11040: No enzyme, likely a non-enzymatic reaction
RMAN3: No enzyme, likely a non-enzymatic reaction
RMAN4: Formate dehydrogenase (EC 1.2.1.2)

R00258: Alanine transaminase (EC 2.6.1.2)
R00400: Alanine---oxo-acid transaminase (EC 2.6.1.1)

Nucleotide Synthesis and Salvage

The following enzymes likely existed in LUCA because nucleotides are the building blocks of DNA and RNA. Thus, their synthesis was crucial for the storage of genetic information, replication, and the emergence of complex biochemical pathways in the earliest life forms.

De novo purine biosynthesis pathway  in LUCA

1. Ribose-phosphate diphosphokinase: Catalyzes the synthesis of PRPP from ribose-5-phosphate and ATP. PRPP is the starting material for the synthesis of purines, pyrimidines, and some amino acids. In LUCA, this enzyme indicates the foundational need to initiate nucleotide synthesis for early genetic material replication and cellular function.
2. Amidophosphoribosyl transferase (GPAT): Catalyzes the transfer of an amide group from glutamine to PRPP, forming 5-phosphoribosylamine (PRA). This step is critical in the purine biosynthesis pathway, underscoring the emergence of purine nucleotides in LUCA to facilitate DNA/RNA synthesis.
3. Glycinamide ribotide (GAR) transformylase (GART): Catalyzes the synthesis of formylglycinamidine ribonucleotide (FGAR) from PRA and glycine. Its presence in LUCA indicates the complexity of biochemical pathways needed for the synthesis of purine nucleotides, vital for early life.
4. Formylglycinamide ribotide (FGAR) amidotransferase (GART): Catalyzes the transfer of a formyl group from N10-formyltetrahydrofolate to FGAR, forming formylglycinamidine ribonucleotide (FGAM). This enzyme's existence in LUCA points towards the intricate metabolic reactions required for producing nucleotide precursors.
5. Formylglycinamidine ribotide (FGAM) synthetase (GART): Catalyzes the synthesis of formylglycinamidine ribonucleotide (FGAR) from FGAM. This enzyme's presence in LUCA suggests an early evolutionary pathway for the production of purine nucleotide precursors.
6. 5-aminoimidazole ribotide (AIR) carboxylase (PurK): Catalyzes the conversion of FGAM to 5-aminoimidazole ribotide (AIR). This enzyme in LUCA reveals the intricate steps involved in the evolution of nucleotide synthesis, essential for DNA and RNA formation.
7. 5-aminoimidazole-4-(N-succinylocarboxamide) ribotide (SACAIR) synthetase (PurE): Catalyzes the synthesis of SACAIR from AIR. Its presence in LUCA indicates the necessity of multiple steps for the biosynthesis of purine nucleotides.
8. Carboxyaminoimidazole ribotide (CAIR) mutase (PurK): Catalyzes the conversion of SACAIR to CAIR. In LUCA, this enzyme showcases the sequential enzymatic reactions needed for the synthesis of purine nucleotides.
9. 5-aminoimidazole-4-carboxamide ribotide (AICAR) transformylase (PurN): Catalyzes the conversion of CAIR to AICAR. Its existence in LUCA suggests a comprehensive enzymatic framework required for nucleotide biosynthesis.
10. 5-formaminoimidazole-4- carboxamide ribotide (FAICAR) cyclase (PurM): Catalyzes the conversion of AICAR to FAICAR. This enzyme in LUCA underscores the sophisticated evolutionary pathways that early life adopted for nucleotide synthesis.
11. IMP cyclohydrolase (PurH): Catalyzes the conversion of FAICAR to inosine monophosphate (IMP). This enzyme's presence in LUCA confirms the culmination of the purine biosynthesis pathway, vital for the formation of DNA and RNA in early cells.

De novo Pyrimidine Synthesis in LUCA

Pyrimidine synthesis is fundamental for the formation of RNA, and thus, the emergence of LUCA. Having a complete pathway ensures the availability of all necessary ribonucleotides for RNA-based genetic storage and transmission in early cellular life.

1. Carbamoyl phosphate synthetase II (CPSII): Catalyzes the ATP-dependent synthesis of carbamoyl phosphate from glutamine or ammonia and bicarbonate. In LUCA, this enzyme initiates the pyrimidine synthesis pathway by providing the precursor molecule, carbamoyl phosphate.
2. Aspartate transcarbamoylase (ATCase): Catalyzes the condensation of carbamoyl phosphate and aspartate to produce N-carbamoylaspartate. This step is crucial for the progression of pyrimidine nucleotide synthesis in LUCA.
3. Dihydroorotase (DHOase): Converts N-carbamoylaspartate into dihydroorotate. This conversion is an essential intermediate step in LUCA's pyrimidine biosynthesis.
4. Dihydroorotate dehydrogenase (DHODH): Oxidizes dihydroorotate to produce orotate. In LUCA, this step represents the formation of the pyrimidine ring structure.
5. Orotate phosphoribosyltransferase (OPRT): Links orotate to 5-phosphoribosyl-1-pyrophosphate (PRPP) to produce orotidine 5'-monophosphate (OMP). This enzyme ensures the incorporation of the synthesized pyrimidine ring into the ribonucleotide structure in LUCA.
6. Orotidine 5'-monophosphate decarboxylase (OMPDC): Catalyzes the decarboxylation of OMP to produce uridine 5'-monophosphate (UMP). This step in LUCA finalizes the synthesis of the primary pyrimidine ribonucleotide.
7. Nucleoside monophosphate kinase (UMP/CMP kinase): Phosphorylates UMP to produce uridine 5'-diphosphate (UDP). In LUCA, this step enriches the pyrimidine nucleotide pool, preparing for further conversions.
8. Nucleoside diphosphate kinase (NDK): Converts UDP to UTP through phosphorylation. UTP is a central pyrimidine nucleotide in LUCA, serving as a precursor for CTP and as an essential component in RNA synthesis.
9. CTP synthetase (CTPS): Catalyzes the conversion of UTP to CTP using glutamine as the nitrogen source. This conversion ensures the availability of both major pyrimidine ribonucleotides in LUCA.

The following enzymes highlight the subsequent steps after IMP synthesis, leading to the formation of adenine and guanine, uracyl, and cytosine ribonucleotides.

the biosynthesis pathways for adenine (A), guanine (G), uracil (U), and cytosine (C) nucleotides, listing the key enzymes involved in each. Remember, nucleotide synthesis often involves shared pathways, especially at the beginning, so some enzymes are involved in the biosynthesis of multiple nucleotides.

Adenine (A) Ribonucleotide Biosynthesis

1. Phosphoribosylaminoimidazole carboxylase (PurE): Converts 5'-phosphoribosyl-5-aminoimidazole (AIR) into 5'-phosphoribosyl-4-carboxy-5-aminoimidazole (CAIR).
2. Adenylosuccinate synthetase (PurA): Synthesizes adenylosuccinate from IMP and aspartate.
3. Adenylosuccinate lyase (PurB): Cleaves adenylosuccinate into AMP and fumarate.

Guanine (G) Ribonucleotide Biosynthesis

1. IMP dehydrogenase (IMPDH): Oxidizes IMP, producing xanthosine monophosphate (XMP).
2. GMP synthetase (GuaA): Converts XMP into GMP using glutamine as a nitrogen source.

Uracil (U) Ribonucleotide Biosynthesis (leading to UMP)

1. Carbamoyl phosphate synthetase II (CPSII): Synthesizes carbamoyl phosphate.
2. Aspartate transcarbamoylase (ATCase): Produces N-carbamoylaspartate from carbamoyl phosphate and aspartate.
3. Dihydroorotase (DHOase): Converts N-carbamoylaspartate to dihydroorotate.
4. Dihydroorotate dehydrogenase (DHODH): Produces orotate by oxidizing dihydroorotate.
5. Orotate phosphoribosyltransferase (OPRT): Links orotate to PRPP, yielding orotidine 5'-monophosphate (OMP).
6. Orotidine 5'-monophosphate decarboxylase (OMPDC): Converts OMP into UMP.

Cytosine (C) Ribonucleotide Biosynthesis (leading to CTP from UTP)

1. Nucleoside monophosphate kinase (UMP/CMP kinase): Converts UMP to UDP.
2. Nucleoside diphosphate kinase (NDK): Phosphorylates UDP, producing UTP.
3. CTP synthetase (CTPS): Transforms UTP to CTP using glutamine as a nitrogen source.

These pathways and enzymes were likely essential in LUCA for the synthesis of RNA, which is central to the storage and transmission of genetic information in early life forms.
Next, the synthesis of thymine nucleotides (as deoxythymidine monophosphate, or dTMP) and then the formation of the deoxyribonucleotides, which are the building blocks of DNA.

Thymine (T) Deoxyribonucleotide Biosynthesis (leading to dTMP from dUMP):

1. Ribonucleotide reductase (RNR): Converts NDPs (nucleoside diphosphates) into dNDPs (deoxynucleoside diphosphates).
2. Dihydrofolate reductase (DHFR): Reduces dihydrofolate to tetrahydrofolate, a crucial cofactor.
3. Thymidylate synthase (TYMS or TS): Methylates dUMP to produce dTMP using the methyl-tetrahydrofolate as a methyl donor, which becomes dihydrofolate after donating its methyl group.

Deoxynucleotide Biosynthesis:

1. Ribonucleotide reductase (RNR): This enzyme, which was also mentioned above, is central to the formation of deoxynucleotides. It catalyzes the conversion of ribonucleotide diphosphates (NDPs) to deoxyribonucleotide diphosphates (dNDPs). The four reactions are:

ADP to dADP
GDP to dGDP
UDP to dUDP
CDP to dCDP

2. Nucleoside diphosphate kinase (NDK): Phosphorylates dNDPs, converting them into their triphosphate forms (dNTPs), which are the actual building blocks used in DNA synthesis.

dADP to dATP
dGDP to dGTP
dUDP to dUTP
dCDP to dCTP

3. dUTPase: Hydrolyzes dUTP to produce dUMP, ensuring a low intracellular concentration of dUTP to prevent its incorporation into DNA.

These pathways and enzymes were instrumental in the emergence of early life forms. The synthesis and availability of both ribonucleotides and deoxynucleotides were essential for LUCA and its descendants, enabling the dual storage of genetic information in RNA and DNA and the diversified functions that come with it.

Total 40 enzymes are required to make deoxynucleotides used in DNA.

Supporting Enzymes and Transporters for the De Novo Purine and Pyrimidine Biosynthesis Pathway in LUCA

1. ATP-binding cassette (ABC) transporters: These transporters use ATP hydrolysis to transport various molecules across cellular membranes. ATP is a necessary cofactor for many enzymatic reactions, including those in purine and pyrimidine biosynthesis.
2. Adenine phosphoribosyltransferase (APRT): Transports adenine by catalyzing its conversion to adenine monophosphate (AMP), which can then enter the purine synthesis pathway.
3. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT): Transports hypoxanthine and guanine by catalyzing their conversion to inosine monophosphate (IMP) and guanosine monophosphate (GMP), respectively.
 Glutamine transporters: As glutamine is both a substrate and a cofactor for enzymes in nucleotide biosynthesis, these transporters help in transporting glutamine into cells.
4. Tetrahydrofolate (THF) and its derivatives: THF is crucial in transferring single carbon units in biosynthetic reactions, including those in purine and pyrimidine biosynthesis. Various enzymes convert dietary folate into its active form, THF, which can then be used in nucleotide synthesis.
5. S-adenosylmethionine (SAM) transporters: SAM is involved in several methylation reactions, including those that modify nucleotides. These transporters help to ensure SAM's availability inside the cell.
6. Amino acid synthetases: While amino acid transporters facilitate the uptake of amino acids, synthetases are responsible for producing those amino acids in the first place. For example, glutamine synthetase produces glutamine, which is crucial for both purine and pyrimidine synthesis.
7. Nucleotidases: These enzymes can hydrolyze nucleotide monophosphates, diphosphates, or triphosphates, producing nucleosides and inorganic phosphates. This ensures a balance between nucleosides and nucleotides within the cell.
8. Dihydrofolate reductase: Converts dihydrofolate (DHF) to tetrahydrofolate (THF), ensuring a supply of the active form of folate for nucleotide synthesis.
9. Purine Transporters: These facilitate the transport of purine bases or nucleosides, which are key precursors for adenine and guanine nucleotide synthesis. Given the ubiquitous nature of purine-containing nucleotides across life, primitive purine transport systems might have been present in LUCA.
10. Pyrimidine Transporters: Similar to purine transporters, these transporters facilitate the movement of pyrimidine bases or nucleosides, which are essential for cytosine, thymine (in DNA), and uracil (in RNA) nucleotide synthesis.
11. Phosphate Transporters: Phosphate is a critical component of nucleotide structure. Efficient uptake of inorganic phosphate from the environment would have been crucial for the synthesis of nucleotides.
12. Ribose/Deoxyribose Transporters: Ribose and deoxyribose sugars are integral parts of RNA and DNA nucleotides, respectively. While cells primarily produce these sugars via the pentose phosphate pathway, transporters specific for ribonucleosides might have existed.

Key Enzymes and Transporters Involved in Tetrahydrofolate THF Synthesis and Metabolism

These are the central enzymes and transporters involved in the metabolism and synthesis of tetrahydrofolate and its derivatives.

1. Dihydrofolate reductase (DHFR): Converts dihydrofolate (DHF) to tetrahydrofolate (THF). This enzyme is pivotal for ensuring a supply of the active form of folate for various cellular processes, including nucleotide synthesis.
2. Serine hydroxymethyltransferase (SHMT): Catalyzes the reversible conversion of serine and THF to glycine and 5,10-methylenetetrahydrofolate. This reaction links amino acid metabolism with folate metabolism.
3. Folate transporters: Ensure the uptake of dietary folates into cells. The dietary folates can then be converted into their active form, THF, within the cell.
4. Folylpolyglutamate synthase (FPGS): Adds glutamate residues to folates, converting them into polyglutamate forms. This enhances folate retention within cells and increases their availability as cofactors.
5. Methylene tetrahydrofolate reductase (MTHFR): Converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is a primary circulating form of folate and a key methyl donor in homocysteine remethylation.
6. Methylene tetrahydrofolate dehydrogenase (MTHFD): Catalyzes the interconversion of various forms of THF, linking purine and pyrimidine synthesis with amino acid metabolism.
7. Gamma-glutamyl hydrolase (GGH): Removes polyglutamates from folates, converting them back to the monoglutamate form which can be exported out of the cell or further metabolized.
8. Folylpoly-gamma-glutamate carboxypeptidase (FTCD): Involved in the breakdown of polyglutamylated folates, ensuring their further metabolism or removal from the cell.
9. Dihydrofolate synthase (DHFS): Converts folate to dihydrofolate (DHF), a precursor of THF.
10. Formyltetrahydrofolate synthetase (FTHFS): Catalyzes the ATP-dependent conversion of formate and THF to 10-formyltetrahydrofolate.

Key Enzymes Involved in S-adenosylmethionine SAM Synthesis and Metabolism

1. Methionine adenosyltransferase (MAT): Converts methionine and ATP to SAM. This enzyme is the primary catalyst for the synthesis of SAM, ensuring a continuous supply for various methyltransferase reactions.
2. S-adenosylhomocysteine hydrolase (SAHH): Hydrolyzes S-adenosylhomocysteine (SAH) to adenosine and homocysteine. This is a reversible reaction, and this enzyme ensures the maintenance of the balance between SAM, SAH, and homocysteine.
3. Methionine synthase (MS): Regenerates methionine from homocysteine using a methyl group from 5-methyltetrahydrofolate. This reaction ensures the recycling of homocysteine to methionine for subsequent conversion to SAM.
4. Betaine-homocysteine methyltransferase (BHMT): Uses betaine as a methyl donor to convert homocysteine to methionine. This provides an alternate pathway for methionine synthesis, especially in the liver.
5. Cystathionine β-synthase (CBS): Converts homocysteine to cystathionine in the first step of the transsulfuration pathway, leading to cysteine synthesis. This ensures the regulation of homocysteine levels and the production of cysteine.
6. Methyltransferases: A vast array of enzymes that use SAM as a methyl donor for the methylation of DNA, RNA, proteins, lipids, and small molecules. They return the byproduct S-adenosylhomocysteine (SAH) after transferring the methyl group.
7. Glycine N-methyltransferase (GNMT): Involved in the regulation of SAM levels by converting glycine and SAM to S-adenosylhomocysteine (SAH) and sarcosine.

These are the main enzymes and transporters involved in the metabolism and synthesis of S-adenosylmethionine and its associated reactions.

Transporters

Magnesium transporters 

Magnesium ions (Mg2+) serve as cofactors for numerous enzymes, including those involved in purine biosynthesis. Specific transport proteins facilitate the uptake of magnesium ions into cells and their delivery to the enzymes that require them. Magnesium (Mg^2+) is fundamental for the function of numerous enzymes and is vital for early cellular life, including the Last Universal Common Ancestor (LUCA). The mechanisms by which LUCA might have maintained magnesium homeostasis are not as well-documented as in modern eukaryotes. However, based on evolutionary traces and the importance of magnesium, one can infer the possible systems involved:

1. Magnesium transporters (Mgt): These would be primary active transport proteins responsible for the uptake of magnesium from the environment. In various modern organisms, Mgt proteins play this role.
2. CorA: This is a well-conserved magnesium transporter family, which facilitates the passive flow of magnesium ions across the cellular membrane. It's plausible that LUCA had a precursor or a version of CorA to help regulate intracellular magnesium levels.
3. Magnesium efflux systems: To prevent magnesium overload, cells would need a system to expel excess magnesium. The details of such a system in LUCA are speculative, but it would be crucial for maintaining magnesium homeostasis.
4. Magnesium-binding proteins: Within the cellular environment, various proteins might bind magnesium, either as a storage mechanism or as part of their functional requirement. This would help in buffering the intracellular magnesium concentration.
5. Magnesium-sensing proteins: For a cell to regulate magnesium concentrations effectively, it would need a way to sense the current magnesium levels. In modern cells, there are magnesium-sensing proteins, and it's plausible that LUCA had an early version or a precursor to these sensors.
6. Enzymatic cofactors: Many enzymes require magnesium as a cofactor. These enzymes would play a role in the intracellular distribution and utilization of magnesium, indirectly influencing its homeostasis.
7. RNA structures: Ribosomal RNA and tRNA, which likely existed in LUCA, bind magnesium ions. This binding helps stabilize their structures and can also play a role in buffering intracellular magnesium levels.

Note: The understanding of magnesium homeostasis in LUCA is based on a combination of direct evidence, evolutionary inference, and the fundamental importance of magnesium in cellular processes. As more research is conducted, the picture of how LUCA maintained magnesium balance might become clearer.

Amino Acid Transporters in LUCA

Some amino acids, like glutamine, play a role in nucleotide synthesis. These transporters ensure the availability of such amino acids by transporting them into the cell.

1. Amino Acid Antiporters: These transport proteins exchange one type of amino acid from the inside of the cell with another from the surrounding environment. It's a type of secondary transport mechanism, capitalizing on gradients set by primary transporters for operation.
2. Amino Acid/H+ Symporters: Involved in the co-transport of an amino acid and a proton into the cell. This process can move nutrients against their concentration gradient by leveraging the movement of ions (like H+) down their gradient.
3. ATP-binding Cassette (ABC) Amino Acid Transporters: These are primary active transporters that use energy from ATP hydrolysis to move amino acids across the cell membrane, irrespective of their concentration gradient.
4. Passive Diffusion: While not a transporter protein per se, some smaller and neutral amino acids might diffuse passively through the cell membrane depending on their concentration gradient.

These transport mechanisms would have been pivotal for LUCA, ensuring the necessary amino acids were available within the cell for protein synthesis and other metabolic processes.

Nucleotide Transporters in LUCA

After the synthesis of purine and pyrimidine nucleotides, these need to be transported to various cellular locations for further use, such as in DNA and RNA synthesis.

1. Nucleotide Antiporters: These transporters exchange one type of nucleotide from inside the cell with another from the external environment. They help maintain a balance of different nucleotides within the cell.
2. Nucleotide/H+ Symporters: These are involved in the co-transport of nucleotides along with protons into the cell. They can move nucleotides against their concentration gradient by using the movement of H+ ions down their gradient.
3. ATP-binding Cassette (ABC) Nucleotide Transporters: These primary transporters use energy from ATP hydrolysis to move nucleotides across the cellular membrane.
4. Nucleotide-specific Channels: These channels can facilitate the passive diffusion of specific nucleotides based on their concentration gradient.
5. Vesicular Transport: Some nucleotides might be enclosed in vesicles and transported to different parts of the cell where they are required.
6. Nucleoside Transporters: While not directly transporting nucleotides, nucleoside transporters are essential for recycling nucleosides, which can then be phosphorylated to regenerate nucleotides inside the cell.
7. P4-ATPases: These are a subset of ATPases that are believed to play a role in the translocation of specific nucleotides across membranes.
8. Facilitated Diffusion Nucleotide Transporters: These allow nucleotides to move down their concentration gradient, assisting their spread within the cell.

These transport mechanisms would have been essential for LUCA, ensuring that synthesized nucleotides were efficiently delivered to various cellular locations for crucial processes such as DNA replication, RNA transcription, and energy transactions.

Nucleoside Transporters in LUCA

Facilitate the uptake of nucleosides like adenosine and guanosine, which can serve as precursors for purine nucleotide synthesis.

1. Concentrative Nucleoside Transporters (CNTs): These are sodium-coupled symporters that transport nucleosides against their concentration gradient, thus concentrating them inside the cell.
2. Equilibrative Nucleoside Transporters (ENTs): These facilitate the passive diffusion of nucleosides across the membrane, moving them down their concentration gradient.
3. ATP-binding Cassette (ABC) Nucleoside Transporters: These primary active transporters utilize the energy from ATP hydrolysis to actively transport nucleosides into or out of the cell.
4. Nucleoside/H+ Symporters: These transporters are involved in the co-transport of nucleosides along with protons, allowing nucleosides to move against their concentration gradient with the help of the proton motive force.
5. Nucleoside Antiporters: These can exchange one type of nucleoside from inside the cell with another type from the external environment.
6. Vesicular Nucleoside Transport: Some nucleosides might be enclosed in vesicles and brought into the cell via endocytosis or moved to other parts of the cell.
7. Specific Channel-formed Nucleoside Transporters: These form channel-like structures that selectively allow specific nucleosides to diffuse into the cell.
8. Nucleoside-specific Pore-forming Proteins: These proteins create pores in the cellular membrane specifically for the passive transport of nucleosides.

Ensuring the proper transport of nucleosides was vital for LUCA as nucleosides are important precursors for nucleotide synthesis. Efficient transport mechanisms would have enabled LUCA to maintain a steady supply of nucleosides for various cellular functions, including DNA replication and energy metabolism.

Phosphate Transporters in LUCA

Phosphate is a key component of nucleotides. These transporters ensure an adequate intracellular supply of phosphate.

1. PiT Family Transporters: These are sodium-phosphate co-transporters that facilitate the symport of inorganic phosphate (Pi) and sodium ions.
2. Pst Phosphate Transport System: This ATP-binding cassette (ABC) transporter complex is highly specific for the uptake of inorganic phosphate.
3. Pho89 Sodium-Phosphate Transporter: A sodium-dependent transporter found in some organisms, responsible for the uptake of inorganic phosphate.
4. Low Affinity Phosphate Transporters: These facilitate the uptake of phosphate when it is abundant in the environment.
5. High Affinity Phosphate Transporters: Crucial during phosphate starvation, these transporters can capture even small amounts of available phosphate.
6. Phosphate Antiporters: Transport systems that can exchange intracellular phosphate with other anions outside the cell.
7. Phosphate/H+ Symporters: Facilitate the uptake of phosphate alongside protons, utilizing the proton motive force for the active uptake of phosphate against its concentration gradient.
8. Vesicular Phosphate Transport: Some cells might employ vesicular mechanisms, like endocytosis, to internalize phosphate-containing compounds.
9. Passive Phosphate Channels: These allow for the passive diffusion of phosphate ions into the cell, usually operating when the extracellular concentration of phosphate is high.

Ensuring a consistent and adequate supply of phosphate was vital for LUCA, as phosphate is not only a critical component of nucleotides but also essential for energy storage and transfer (as in ATP) and various other cellular processes. Proper phosphate transport mechanisms would have been key to the survival and growth of early cellular life forms.

Folate Transporters in LUCA

Folate is a cofactor essential for one-carbon metabolism, which plays a pivotal role in nucleotide synthesis. These transporters ensure folate is available inside the cell.

1. Folate-Binding Protein (FBP) Transporters: These proteins bind folates with high affinity and facilitate their transport into cells.
2. Proton-Coupled Folate Transporter (PCFT): A major transporter for folate uptake, especially in the acidic pH conditions of certain cellular environments.
3. Reduced Folate Carrier (RFC): Facilitates the transport of reduced folates into cells and is vital for maintaining intracellular folate homeostasis.
4. Multidrug Resistance Protein (MRP) Transporters: While primarily involved in drug resistance, some members of the MRP family can also transport folate compounds.
5. Folate Receptors (FRs): These are glycosylphosphatidylinositol-anchored proteins that can bind folate and related compounds, facilitating their uptake via endocytosis.
6. ABC Transporters: Some members of the ATP-binding cassette (ABC) transporter family have been implicated in the transport of folate or folate analogs.

Ensuring adequate uptake and availability of folate was likely pivotal for LUCA, given the central role of folate in one-carbon metabolism and its significance for nucleotide synthesis. The right transport mechanisms would have been instrumental in maintaining cellular folate levels and ensuring smooth functioning of various biochemical pathways reliant on folate.

SAM Transporters in LUCA

Transport SAM across various cellular compartments, ensuring its availability to enzymes that require it for methylation reactions.

1. SAM Transporter (SAMT): Specialized transporters that mediate the movement of S-adenosylmethionine (SAM) across the cellular membranes, ensuring its availability in various compartments for methylation reactions.
2. ATP-Binding Cassette (ABC) Transporters: Some members of the ABC transporter family are known to transport SAM, among other molecules, across cellular membranes.
3. Mitochondrial SAM Transporters (SAMC): Facilitate the import of SAM into mitochondria, an essential process given that many methylation reactions occur within this cellular compartment.
4. Solute Carrier Family Transporters: Some members of the solute carrier (SLC) family have shown the potential to transport SAM, although their role in LUCA is speculative.
5. Multidrug Resistance Proteins (MRPs): While their primary function is related to drug resistance, some MRPs can also transport SAM and other related compounds across membranes.
6. Vesicular Transport Mechanisms: SAM might be packaged into vesicles and shuttled to different cellular locations, ensuring its availability for various enzymatic reactions.

The transport of SAM to the right cellular compartments in LUCA would have been vital, given SAM's central role as a methyl group donor in numerous biochemical reactions. Efficient transport mechanisms would ensure that SAM is readily available wherever methylation reactions are taking place, promoting metabolic fluidity and cellular function.

Carbon Source Transporters in LUCA

1. Glucose/Galactose Transporter (GLUT): Mediates the uptake of glucose into cells, fueling pathways like glycolysis and the pentose phosphate pathway, the latter generating ribose-5-phosphate for nucleotide synthesis.
2. ATP-Binding Cassette (ABC) Glucose Transporters: Active transporters in the ABC family that specifically transport glucose molecules into the cell against concentration gradients.
3. Hexose Transporter (HXT): Facilitates the uptake of various hexoses, including glucose, into the cell. These hexoses can contribute to nucleotide precursor pathways.

Amino Acid Precursors for Nucleotide Synthesis Transporters in LUCA

4. Glutamine Transporters: Facilitates the uptake of glutamine, which plays a significant role in purine and pyrimidine nucleotide synthesis.
5. Aspartate Transporters: Mediates the uptake of aspartate, a precursor for pyrimidine nucleotide synthesis.
6. Glycine Transporters (GlyT): Ensures the availability of glycine, which is required for purine nucleotide synthesis.

Co-factor Transporters for Nucleotide Synthesis in LUCA

7. Vitamin B6 Transporters: Facilitates the uptake of Vitamin B6, a co-factor in various reactions, including those involved in nucleotide metabolism.
8. Tetrahydrofolate (THF) Transporters: Mediate the uptake and distribution of THF, a key co-factor in one-carbon metabolism essential for nucleotide synthesis.

Ion Transporters in LUCA with Relevance to Nucleotide Synthesis

9. Potassium (K+) Transporters: Maintains the proper intracellular potassium concentration, critical for many enzymes involved in nucleotide metabolism.
10. Zinc (Zn2+) Transporters: Ensures intracellular availability of zinc, a crucial cofactor for several enzymes in nucleotide biosynthesis pathways.

While these transporters are indirectly associated with nucleotide synthesis, they play a foundational role by ensuring the required precursors and co-factors are available for the biosynthetic pathways.

Glutamine transporters

As glutamine is both a substrate and a cofactor for enzymes in nucleotide biosynthesis, these transporters help in transporting glutamine into cells.

1. System N Transporters (SNATs): Early forms of these transporters may have facilitated the movement of glutamine, aiding in nitrogen balance and supporting the synthesis of nucleotides. Glutamine, being rich in nitrogen, would be a key substrate for the production of nucleotide precursors in LUCA.
2. System A Transporters (SAATs): Potentially primordial versions of these transporters could have ensured the uptake of small neutral amino acids, including glutamine. Their presence would support LUCA's need for efficient nutrient acquisition in the competitive prebiotic milieu.
3. System L Transporters: Their potential relevance to LUCA lies in their ability to transport both large neutral and bulky amino acids. Efficient transport mechanisms like these would have been crucial for LUCA to synthesize proteins and other biomolecules using diverse amino acid substrates, including glutamine.

Relevance to LUCA: The very existence of specific transporters for glutamine in LUCA indicates the pivotal role this amino acid might have played in early cellular metabolism. Given that nucleotide synthesis is fundamental for DNA and RNA replication and synthesis, having a dedicated system for the transport of glutamine—a critical cofactor and substrate—reflects its evolutionary importance. The presence of these transporters in LUCA hints at early cellular mechanisms prioritizing the efficient synthesis and regulation of nucleotides, setting the stage for the complex life processes that would evolve subsequently.

1. Ribose ABC Transporters: As part of the ATP-Binding Cassette (ABC) transporter family, these proteins could have actively transported ribose into cells using ATP. The presence of ABC transporters specific for ribose would have been vital for ensuring a steady supply of this essential sugar for nucleotide synthesis in LUCA.
2. Ribose-Proton Symporters: Leveraging the gradient of protons across the membrane, these transporters might have facilitated the co-transport of ribose into the cell. Such a mechanism would have provided an energy-efficient way of accumulating ribose from the environment, especially if external concentrations were low.
3. Facilitated Ribose Transporters: These passive transporters could have allowed the diffusion of ribose down its concentration gradient into the cell. Their presence in LUCA would suggest a primordial method of nutrient uptake without the direct expenditure of cellular energy.

Relevance to LUCA: The incorporation of ribose into the growing nucleotide chain is one of the defining features of life as we understand it. Having transporters dedicated to the uptake of ribose indicates the importance of this sugar in early cellular biochemistry. For LUCA, an organism that stands at the dawn of cellular life, ensuring a consistent and efficient supply of ribose would have been paramount. The existence of these transporters in LUCA not only underscores the central role of nucleotides in early life but also suggests a highly regulated system for their synthesis right from the beginning.

Ribose transporters

Ribose, a sugar component, is crucial for nucleotide synthesis. These transporters facilitate its uptake into cells.

1. Ribose ABC Transporters: As part of the ATP-Binding Cassette (ABC) transporter family, these proteins could have actively transported ribose into cells using ATP. The presence of ABC transporters specific for ribose would have been vital for ensuring a steady supply of this essential sugar for nucleotide synthesis in LUCA.
2. Ribose-Proton Symporters: Leveraging the gradient of protons across the membrane, these transporters might have facilitated the co-transport of ribose into the cell. Such a mechanism would have provided an energy-efficient way of accumulating ribose from the environment, especially if external concentrations were low.
3. Facilitated Ribose Transporters: These passive transporters could have allowed the diffusion of ribose down its concentration gradient into the cell. Their presence in LUCA would suggest a primordial method of nutrient uptake without the direct expenditure of cellular energy.

Relevance to LUCA: The incorporation of ribose into the growing nucleotide chain is one of the defining features of life as we understand it. Having transporters dedicated to the uptake of ribose indicates the importance of this sugar in early cellular biochemistry. For LUCA, an organism that stands at the dawn of cellular life, ensuring a consistent and efficient supply of ribose would have been paramount. The existence of these transporters in LUCA not only underscores the central role of nucleotides in early life but also suggests a highly regulated system for their synthesis right from the beginning.

Organic cation/carnitine transporters

These assist in the uptake of various organic cations, some of which can be used in nucleotide synthesis.

1. Organic Cation Transporter (OCT) Family: Members of this family are polyspecific transporters that can recognize and transport a broad range of structurally unrelated organic cations. Their presence in LUCA would have enabled the early cell to uptake multiple useful cations from the environment, some of which are precursors or cofactors for nucleotide synthesis.
2. Carnitine/Organic Cation Transporter (OCTN) Family: This subgroup of transporters specifically recognizes carnitine in addition to other organic cations. Carnitine, while best known for its role in lipid metabolism, may have played roles in early metabolic pathways, and its uptake would be essential for primitive cells.
3. High-Affinity Carnitine Transporters: Dedicated transporters for carnitine uptake might have existed in LUCA, suggesting the importance of carnitine in early cellular biochemistry, potentially beyond its well-known function in lipid transport.

Relevance to LUCA: Organic cation transporters, by ensuring the uptake of a variety of organic cations, would have provided LUCA with a versatile toolset for interacting with its environment. The ability to accumulate essential precursors and cofactors for nucleotide synthesis would have been particularly critical for the replication and survival of early cellular life forms. The inclusion of carnitine transporters highlights the potential diversity of early metabolic pathways and the importance of acquiring various organic molecules from the surrounding milieu.

Nucleotide Salvage Pathways

Purine Catabolism

1. Adenosine deaminase (ADA): This enzyme is responsible for the conversion of adenosine to inosine.
2. Purine nucleoside phosphorylase (PNP): This enzyme converts inosine to hypoxanthine and guanosine to guanine.
3. Guanase: Involved in the conversion of guanine to xanthine.
4. Xanthine oxidase: This enzyme facilitates the conversion of hypoxanthine to xanthine and xanthine to uric acid.
5. AMP deaminase: Converts AMP to IMP.

Pyrimidine Catabolism

1. Cytidine deaminase: Converts cytidine to uridine.
2. Nucleoside phosphorylases: These enzymes release ribose 1-phosphate from uridine and thymidine, yielding uracil and thymine, respectively.
3. Dihydropyrimidinase: This enzyme is involved in the conversion of dihydrouracil to β-ureidopropionic acid.
4. β-Ureidopropionase: Converts β-ureidopropionic acid to β-alanine.
5. Thymidine kinase (TK): Phosphorylates thymidine to form thymidine monophosphate (TMP).
6. Thymidylate synthase: Involved in the conversion of TMP to dTMP.

1. Ribonucleotide reductase (RNR): This enzyme is crucial for the conversion of ribonucleotides to deoxyribonucleotides, playing a key role in maintaining deoxynucleotide levels.
2. Deoxynucleotidases: These enzymes hydrolyze deoxynucleotides to produce the corresponding deoxynucleosides.
3. Deoxynucleoside kinases: Responsible for the phosphorylation of deoxynucleosides, converting them back to deoxynucleotides.

References

● Oró, J., & Kimball, A.P. (1962). Synthesis of purines under possible primitive earth conditions: II. Purine intermediates from hydrogen cyanide. Archives of Biochemistry and Biophysics, 96(2), 293-313. Link. (This research discusses the potential synthesis of purine intermediates from hydrogen cyanide, providing insights into the early biochemical pathways that may have led to nucleotide synthesis under primitive Earth conditions.)

////  provide me with  BBCode formatted references on the topics mentioned above. I'd like them in chronological order, in the following format:

1. McLaren, A. (2003). Primordial germ cells in the mouse. Developmental Biology, 262(1), 1-15. Link. (This seminal paper provides an overview of germ cell development in mice, a common model organism.)
2. Raz, E. (2003). Primordial germ-cell development: the zebrafish perspective. Nature Reviews Genetics, 4(9), 690-700. [/size]Link. (Offers a comparative look using zebrafish, highlighting the conserved and unique mechanisms across species.)
aspartate is the initial precursor for threonine biosynthesis.

"Please provide a scientific explanation..."
"Could you write a factual and precise account..."
"I need an academic-style write-up..."
I want it to be in a continuous, a narrative format without using repetitive or flowery language. i want an “objective,” “formal,” or “scientific” tone for a straightforward and factual text.


////  provide a list of key enzymes and proteins involved in the specified pathway based on the information available to you.

///// "Please provide a scientific explanation..."
"Could you write a factual and precise account..."
"I need an academic-style write-up..."
I want it to be in a continuous, a narrative format without using repetitive or flowery language. i want an “objective,” “formal,” or “scientific” tone for a straightforward and factual text. underline the name of the enzymes in the text, write in bbcode. When you finish the text, never write: in summary. Just summarize, without mentioning it. Like this:
never use bolt, only underline, to mention the enzymes.

In the intricate arena of DNA modification and regulation, several essential players contribute to the maintenance and management of genomic stability and function. These key molecular components ensure the proper organization, structuring, and regulation of DNA, crucial for accurate genetic expression and cellular functionality. Chromosome Segregation SMC is considered to significantly influence chromosome partitioning. It holds a reputed role in assuring the proper and efficient segregation of chromosomes during the vital process of cell division. This function is fundamental for maintaining genetic continuity and integrity, preventing chromosomal anomalies that could result in cellular dysfunction. DNA Methyltransferase is a pivotal enzyme in the DNA modification landscape.




For each enzyme or protein, provide the following information:
Name of the enzyme or protein
EC number (if available)
Brief description of the function
Search for each enzyme or protein in a database like KEGG to find the corresponding Reaction number (R number) and URL. those that dont have, use wikipedia.  Information up to 2021 is ok. i don't need direct links or real-time, up-to-date . data available to you up until your training data cut-off in September 2021 is fine with me.  List it in this format ,   list  exactly in a sequential or logical order if possible. i need a comprehensive list, all acessory proteins listed, in    bbcode:
If there is no keggs or ec code, just write the enzyme name, and its function( just write it, do not mention: function)  

DnaA: Initiator protein for DNA replication, binds to the origin of replication and unwinds DNA.
DiaA: Regulates the initiation of chromosomal replication via direct interactions with DnaA.




Search for each enzyme or protein in a database like KEGG to find the corresponding Reaction number (R number) and URL. Information up to 2021 is ok. i don't need direct links or real-time, up-to-date . data available to you up until your training data cut-off in September 2021 is fine with me. provide me that one. List it in this format , bbcode:
If there is no keggs or ec code, just write the enzyme name, and its function( just write it, do not mention: function)

Biosynthesis and Assembly of the Bacterial Ribosome

The biosynthesis and assembly of the E. coli ribosome are complex, multistep processes that involve the coordinated synthesis and assembly of rRNAs and ribosomal proteins, along with the participation of various assembly factors and enzymes. Below is an outline of the major steps involved in ribosome biosynthesis and assembly in E. coli:

I. rRNA Synthesis

rRNA Transcription: RNA polymerase synthesizes a long rRNA precursor (30S pre-rRNA) that contains the sequences of 16S, 23S, and 5S rRNAs. This transcription is regulated by various factors.





II. rRNA Processing

Endonucleolytic Cleavage: RNase III cleaves the large rRNA precursor into smaller fragments.
Exonucleolytic Trimming: Additional RNases (e.g., RNase G) further process the rRNA fragments to produce mature 16S, 23S, and 5S rRNAs.

III. rRNA Modification

Methylation: Methyltransferases (e.g., RsmA/KsgA and RsmB) modify specific bases and ribose sugars within the rRNAs.
Pseudouridylation: Enzymes convert specific uridine residues to pseudouridine.

IV. Ribosomal Protein Synthesis

Translation: Ribosomal proteins are synthesized by the existing ribosomes.
Transport: Ribosomal proteins are transported to the nucleoid region where ribosome assembly occurs.

V. Small Subunit (30S) Assembly

16S rRNA and Protein Association: 16S rRNA associates with small subunit ribosomal proteins (e.g., RpsA, RpsB, RpsC, RpsD, RpsE).
Assembly Factors: Proteins like RimM and RimP aid in the correct folding and assembly of the 30S subunit.
Maturation: Final adjustments and modifications ensure the correct structure and function of the 30S subunit.

VI. Large Subunit (50S) Assembly

23S and 5S rRNA and Protein Association: 23S and 5S rRNA associate with large subunit ribosomal proteins.
Assembly Factors: Various other proteins and factors assist in the assembly of the 50S subunit.
Maturation: Final adjustments and modifications ensure the correct structure and function of the 50S subunit.

VII. 70S Ribosome Assembly:

Subunit Association: The 30S and 50S subunits associate to form the functional 70S ribosome.
Functional Checking: The assembled 70S ribosome is checked for functionality, and any incorrectly assembled ribosomes are recycled.

VIII. Quality Control and Recycling:

Surveillance and Correction: Quality control mechanisms monitor the assembly process, and incorrectly assembled subunits are recycled or degraded.

This is a basic outline, and each step involves additional complexities, including the participation of various additional proteins and factors, and the exact mechanisms and components can vary. Further details can be found in specialized literature and resources on ribosome biosynthesis and assembly.

Sigma Factors:

σ70: Recognizes specific promoter sequences and ensures efficient RNA polymerase binding.
σ38 (RpoS): Regulates genes in response to various stress responses.
σ32: Involved in the heat shock response.
σ28: Involved in flagellar gene expression.
σ24: Involved in the expression of genes during the stationary phase.
σ19: Involved in the expression of flagellar genes in some bacteria.
DNA Compaction and Bending:
IHF: Involved in DNA compaction and bending, assisting in the formation of complex nucleoprotein structures.

HU: Binds to DNA and induces bending, plays a role in the structure and regulation of bacterial nucleoids.
Fis: Involved in the control of DNA replication as well as regulation of rRNA transcription.

Catabolite Repression and Activation:

CAP (Catabolite Activator Protein): Regulates the transcription of operons in response to changes in cyclic AMP (cAMP) levels.

Stress Response:

LexA: Represses genes involved in the SOS response, a global response to DNA damage.

RpoS (Sigma S): Regulates many genes in response to various stress responses.
FNR: Global transcriptional regulator involved in the switch between anaerobic and aerobic metabolism.
HdfR: Regulates genes involved in the catabolism of formaldehyde.
SoxR: Regulates the expression of genes involved in response to oxidative stress.
Fur (Ferric Uptake Regulator): Regulates iron uptake genes in response to iron availability.
Rob: Involved in the regulation of drug resistance and lipid metabolism genes.

Nutrient Metabolism and Uptake

CRP (cAMP Receptor Protein): Involved in catabolite repression, enhancing the expression of numerous genes.

NarL: Involved in the regulation of nitrate and nitrite metabolism.
Lrp: Leucine-responsive regulatory protein, involved in the regulation of many genes including those of amino acid biosynthesis pathways.
OmpR: Response regulator in a two-component system with EnvZ, involved in osmoregulation.
RbsR: Regulates genes involved in ribose transport and metabolism.
MetJ: Repressor for the methionine biosynthetic pathway.
PurR: Regulates purine biosynthesis.
GadE: Activates genes involved in the glutamate-dependent acid resistance system.
ArgR: Regulates the transcription of genes and operons involved in arginine metabolism.

Other Functions

QseB: Response regulator in a two-component system involved in the regulation of flagella and motility genes.

QseC: Sensor kinase in a two-component system with QseB.
RcsB: Response regulator involved in the regulation of capsule biosynthesis.
RcsC: Sensor kinase in a two-component system with RcsB.
RcsD: Phosphorelay protein involved in the Rcs phosphorelay system.
NtrC (Nitrogen Regulator I): Involved in nitrogen regulation and nitrogen assimilation.
FlhD: Part of the FlhD/FlhC complex, involved in the regulation of flagellar biosynthesis.
DnaA: Initiator of chromosomal replication, binds specifically to the dnaA box in the origin of chromosomal replication.
FtsZ: Essential for cell division, assembles as a ring at the future division site.
NrdR: Regulator of ribonucleotide reductase genes.

Signal Detection and Response

SdiA: Detects acyl-homoserine lactone (AHL) signals from other bacterial species.
Sigma Factors:
RpoN (Sigma-54): Binds to a distinct DNA sequence and controls transcription of specific genes.
RpoD (Sigma-70): The primary sigma factor during exponential growth.
Two-Component System Regulators:
TorR: Response regulator in a two-component system with TorS, involved in torCAD operon expression.
CheY: Involved in chemotaxis, receives signals from the chemotaxis sensory apparatus.
PhoP: Part of a two-component system with PhoQ, involved in the regulation of phosphate uptake and virulence.
CpxR: Response regulator in the CpxA-CpxR two-component system, involved in envelope stress response.
ZraR: Response regulator in a two-component system with ZraS, involved in zinc resistance.
KdpE: Response regulator in the KdpD/KdpE two-component system, controls expression of the kdpFABC operon.
BaeR: Response regulator in a two-component system with BaeS, involved in the regulation of multidrug efflux systems.
NarP: Response regulator in a two-component system with NarQ, involved in nitrate and nitrite regulation.
QseB: Response regulator in a two-component system involved in the regulation of flagella and motility genes.
ZntR: Regulator of zinc transport systems.
CueR: Regulates copper homeostasis genes.
PmrA: Response regulator in a two-component system with PmrB, involved in resistance to polymyxin B.
ArcA: Response regulator in the ArcB-ArcA two-component system, involved in aerobic/anaerobic regulation.
ModE: Regulates molybdenum transport and metabolism genes.

Metabolic Regulation

BirA: Biotin operon repressor and biotin ligase.
MalT: Activator of the maltose regulon.
NagC: Repressor for the N-acetylglucosamine utilization operon.
GalR: Repressor for the galETKM operon, involved in galactose metabolism.
GadX: Involved in the regulation of acid resistance genes.
GcvA: Regulator of the glycine cleavage system.
CitB: Involved in the regulation of citrate fermentation.
FimZ: Involved in the regulation of type 1 fimbriae expression.
GerE: Involved in spore coat synthesis.

Flagellar Gene Regulation

FlhC: Works with FlhD to regulate flagellar gene expression.

Stress Response and General Regulation

PspF: Regulates phage shock protein expression.
SoxS: Regulates the expression of genes involved in response to oxidative stress.
YedW: Involved in the control of redox maintenance.
MlrA: Involved in regulating genes for biofilm formation.
SlyA: Regulator involved in virulence and stress response.
YqhC: Regulates genes involved in quinone and alcohol metabolism.

Metabolic Regulation

GutM: Involved in the regulation of glucitol metabolism.
HdfR: Regulates genes involved in the catabolism of formaldehyde.
Fnr: Global transcriptional regulator involved in anaerobic growth.
AppY: Activator of anaerobically induced genes.
NagC: Repressor of the N-acetylglucosamine (GlcNAc) operon.
GalR: Repressor for the galETKM operon, involved in galactose metabolism.
AsnC: Regulates asparagine and aspartate biosynthesis.
FadR: Regulates fatty acid degradation.
GlpR: Repressor of the glycerol regulon.
DgsA: Glucose sensing protein.
OxyR: Hydrogen peroxide sensing protein.
Mlc: Repressor of the phosphotransferase system.
MarA: Involved in regulating antibiotic resistance genes.
MarR: Regulates the mar operon involved in multiple antibiotic resistance.
MelR: (No direct Wikipedia page) Activator of melAB operon, involved in melibiose metabolism.
MetR: Activator of methionine biosynthesis genes.
Mlc: (No direct Wikipedia page) Regulates the phosphotransferase system.
MlrA: (No direct Wikipedia page) Involved in regulating genes for biofilm formation.
NagC: Repressor of the nag operon involved in N-acetylglucosamine metabolism.
NhaR: Regulator of sodium/proton antiporter gene expression.
NirC: Regulates genes involved in nitrite extrusion.
NorR: Regulates nitric oxide reductase gene expression.
OxyR: (No direct Wikipedia page) Regulates response to oxidative stress.
PdhR: Pyruvate dehydrogenase complex regulator.
PurR: Repressor of purine biosynthesis genes.
Rob: Regulator of drug resistance and lipid metabolism genes.
RcsA: Regulates capsule synthesis.
SlyA: Regulator involved in virulence and stress response.
TorR: TMAO reductase operon regulator.
UlaR: Regulator of the L-ascorbate utilization operon.
YbjK: (No direct Wikipedia page) Involved in regulating the expression of various genes.
YebC: Putative transcriptional regulator.
YeiE (CusR): (No direct Wikipedia page) Regulates copper and silver efflux systems.
YfeA: Involved in the yfe operon related to iron efflux.
YieP (CpxR): (No direct Wikipedia page) Involved in envelope stress response.
YeaM: A member of the YedW/YeaM oxidative stress regulatory system.
BirA: Biotin operon repressor and biotin ligase.
AsnC: Regulates asparagine and aspartate biosynthesis.
YbjQ: Putative transcriptional regulator.
Nac: Nitrogen assimilation control protein.
FadR: Regulates fatty acid degradation.
NarL: Involved in nitrate and nitrite metabolism regulation.
MalT: Activator of the maltose regulon.
GlpR: Repressor of the glycerol regulon.
DgsA: Glucose sensing protein.
OxyR: Hydrogen peroxide sensing protein.
Mlc: Repressor of the phosphotransferase system.
NagC: Repressor of the N-acetylglucosamine (GlcNAc) operon.
DnaA: Initiator of chromosomal replication.
MarA: Involved in regulating antibiotic resistance genes.
MarR: Regulates the mar operon involved in multiple antibiotic resistance.
MelR: (No direct Wikipedia page) Activator of melAB operon, involved in melibiose metabolism.
MetR: Activator of methionine biosynthesis genes.
Mlc: (No direct Wikipedia page) Regulates the phosphotransferase system.
MlrA: (No direct Wikipedia page) Involved in regulating genes for biofilm formation.
NagC: Repressor of the nag operon involved in N-acetylglucosamine metabolism.
NhaR: Regulator of sodium/proton antiporter gene expression.
NirC: Regulates genes involved in nitrite extrusion.
NorR: Regulates nitric oxide reductase gene expression.
OxyR: (No direct Wikipedia page) Regulates response to oxidative stress.
PdhR: Pyruvate dehydrogenase complex regulator.
PurR: Repressor of purine biosynthesis genes.
Rob: Regulator of drug resistance and lipid metabolism genes.
RcsA: Regulates capsule synthesis.
SlyA: Regulator involved in virulence and stress response.
TorR: TMAO reductase operon regulator.
UlaR: Regulator of the L-ascorbate utilization operon.
YbjK: (No direct Wikipedia page) Involved in regulating the expression of various genes.
YebC: Putative transcriptional regulator.
YeiE (CusR): (No direct Wikipedia page) Regulates copper and silver efflux systems.
YfeA: Involved in the yfe operon which is related to iron efflux.
YieP (CpxR): (No direct Wikipedia page) Involved in envelope stress response.
YqhC: Regulates genes involved in quinone and alcohol metabolism.
ZntR: (No direct Wikipedia page) Regulates the zinc transporter ZntA.
Zur: Zinc uptake regulator, involved in zinc homeostasis.
ZraR: Regulates zinc-responsive anti-sigma factor.
GcvA: Regulates genes involved in glycine catabolism.
MalT: Activator of maltose regulon.
GlnG (NtrC): Nitrogen regulation, involved in the regulation of nitrogen assimilation genes.
Mlc: (No direct Wikipedia page) Regulates the phosphotransferase system.
MlrA: (No direct Wikipedia page) Involved in regulating genes for biofilm formation.
NagC: Repressor of the nag operon involved in N-acetylglucosamine metabolism.
NhaR: Regulator of sodium/proton antiporter gene expression.
NirC: Regulates genes involved in nitrite extrusion.
NorR: Regulates nitric oxide reductase gene expression.
OxyR: (No direct Wikipedia page) Regulates response to oxidative stress.
PdhR: Pyruvate dehydrogenase complex regulator.
PurR: Repressor of purine biosynthesis genes.
Rob: Regulator of drug resistance and lipid metabolism genes.
RcsA: Regulates capsule synthesis.
SlyA: Regulator involved in virulence and stress response.
TorR: TMAO reductase operon regulator.
UlaR: Regulator of the L-ascorbate utilization operon.
YbjK: (No direct Wikipedia page) Involved in regulating the expression of various genes.
YebC: Putative transcriptional regulator.
YeiE (CusR): (No direct Wikipedia page) Regulates copper and silver efflux systems.
YfeA: Involved in the yfe operon related to iron efflux.
YieP (CpxR): (No direct Wikipedia page) Involved in envelope stress response.
YqhC: Regulates genes involved in quinone and alcohol metabolism.
ZntR: (No direct Wikipedia page) Regulates the zinc transporter ZntA.
Zur: Zinc uptake regulator, involved in zinc homeostasis.
ZraR: Regulates zinc-responsive anti-sigma factor.
GcvA: Regulates genes involved in glycine catabolism.
MalT: Activator of maltose regulon.
GlnG (NtrC): Nitrogen regulation, involved in the regulation of nitrogen assimilation genes.

Other Regulatory Proteins

RcsA: Auxiliary protein that works with RcsB to regulate capsule synthesis.
RyhB: Small RNA involved in the regulation of iron storage and utilization.
FlhD: Regulates genes involved in flagellar synthesis.
HydG: Involved in hydrogenase-3 synthesis.
Fis: Involved in the control of DNA replication as well as regulation of rRNA transcription.
NsrR: Regulates genes in response to nitric oxide.
GlnG (NtrC): Involved in nitrogen assimilation control.
AdiY: Regulator of the arginine-dependent acid resistance system.
YfhA: Involved in the regulation of iron-sulfur cluster assembly.

//// Search for all  proteins  in a database like KEGG to find the corresponding Reaction number (R number) and URL. those who don't have, use Wikipedia. I don't need direct links or real-time, up-to-date Information up to 2021 is ok.  . data available to you up until your training data cut-off in September 2021 is fine with me.  I need a sequential or logical order if possible. i need a comprehensive list,   sorted out in to what metabolic pathway each protein family belongs,  in    bbcode:
If there is no keggs or ec code, link to a wikipedia page that describes the players, or any science paper. Otherwise,  just write the name, and its function( just write it, do not mention: function) . Write in bbcode, like this:
point out, how many times the protein family is listed as possibly extant in luca ( + ), and how many times as probably not extant (-).

Amino acid transport and metabolism (3 extant, 5 not extant)
COG0001 - Glutamyl-tRNA(Gln) amidotransferase subunit A: Involved in the indirect tRNA aminoacylation pathway.


COG0001 -  Glutamyl-tRNA(Gln) amidotransferase subunit A:  Amino acid transport and metabolism:  Involved in the indirect tRNA aminoacylation pathway. (3 extant, 5 not extant)
COG0002 -  Glutamyl-tRNA(Gln) amidotransferase subunit A:  Amino acid transport and metabolism:  Involved in the indirect tRNA aminoacylation pathway. (3 extant, 5 not extant)




COG0004 (2 extant, 6 not extant) - Amino acid transport and metabolism 

 
Arginase: Catalyzes the hydrolysis of arginine to ornithine and urea.


COG0002 (3 extant, 5 not extant) - Lipid transport and metabolism
Acetyl-coenzyme A carboxylase carboxyl transferase subunit beta: Catalyzes the carboxylation of acetyl-CoA to malonyl-CoA.
COG0005 (4 extant, 4 not extant) - Nucleotide transport and metabolism
Adenylate kinase: Involved in regulating the adenine nucleotide composition within a cell.

DNA Replication:

DnaA: Initiator protein for DNA replication, binds to the origin of replication and unwinds DNA. (Listed as extant in LUCA: 3 times)
Carbohydrate Metabolism:
2. Eco:b2926: Enzyme involved in carbohydrate metabolism. (Listed as extant in LUCA: 2 times, Listed as probably not extant in LUCA: 2 times)

Amino Acid Metabolism:
3. Eco:b2578: Involved in amino acid metabolism. (Listed as probably not extant in LUCA: 1 time)

Lipid Metabolism:
4. Eco:b0009: Involved in lipid metabolism. (Listed as probably not extant in LUCA: 3 times)

Signal Transduction:
5. Eco:b4397: Protein involved in signal transduction. (Listed as probably not extant in LUCA: 1 time)

Energy Production and Conversion:
6. Eco:b1220: Involved in energy production and conversion. (Listed as extant in LUCA: 2 times)

Eco:b2925: Involved in energy production and conversion. (Listed as extant in LUCA: 3 times)
Eco:b2926: Enzyme involved in energy production and conversion. (Listed as extant in LUCA: 2 times, Listed as probably not extant in LUCA: 2 times)
Transport and Catabolism:
9. Eco:b2577: Involved in transport and catabolism. (Listed as probably not extant in LUCA: 1 time)

Amino acid transport and metabolism 


COG0001 - Not found in the database. 
COG0002 - Glutamyl-tRNA(Gln) amidotransferase subunit A: Involved in the indirect tRNA aminoacylation pathway. (1 extant, 7 not extant) 
COG0004 - Not found in the database. 
COG0005 - Not found in the database. 
COG0006 - Xaa-Pro aminopeptidase: Involved in the release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide. (6 extant, 2 not extant) 

Translation, ribosomal structure and biogenesis 


COG0001 - Not found in the database. COG0002 - Glutamyl-tRNA(Gln) amidotransferase subunit A: Involved in the indirect tRNA aminoacylation pathway. (1 extant, 7 not extant)


Energy production and conversion 


COG0002 - Glutamyl-tRNA(Gln) amidotransferase subunit A: Involved in the indirect tRNA aminoacylation pathway. (1 extant, 7 not extant) 
COG0008 - Not found in the database.


Amino acid transport and metabolism 


COG0017 - Aspartyl/asparaginyl-tRNA synthetase: Involved in aspartyl-tRNA and asparaginyl-tRNA aminoacylation. (4 extant, 4 not extant) 
COG0018 - Arginyl-tRNA synthetase: Involved in arginyl-tRNA aminoacylation. (5 extant, 3 not extant)


Energy production and conversion 


COG0019 - Diaminopimelate decarboxylase: Involved in lysine biosynthetic process via diaminopimelate. (5 extant, 3 not extant) 
COG0020 - Pyruvate dehydrogenase E1 component subunit beta: Involved in pyruvate metabolic process. (4 extant, 4 not extant)


Translation, ribosomal structure and biogenesis 


COG0021 - Translation initiation factor 1 (eIF-1/SUI1): Involved in translation initiation. (3 extant, 5 not extant) 
COG0022 - [url=https://www.ncbi.nlm.nih.gov/research/cog/pathway/Pyruvate oxidation/]Pyruvate/2-oxoglutarate/acetoin dehydrogenase complex, dehydrogenase (E1) component, beta subunit[/url]: Involved in pyruvate oxidation. (2 extant, 6 not extant)


Posttranslational modification, protein turnover, chaperones 


COG0023 - Protein not found: No information available. (0 extant, 8 not extant) 
COG0024 - Methionine aminopeptidase 1: Involved in protein initiator methionine removal. (5 extant, 3 not extant)


Inorganic ion transport and metabolism 


COG0026 - Protein not found: No information available. (4 extant, 4 not extant) 
COG0027 - Protein not found: No information available. (5 extant, 3 not extant)


Signal transduction mechanisms 


COG0028 - Protein not found: No information available. (3 extant, 5 not extant) 
COG0029 - 16S rRNA A1518 and A1519 N6-dimethyltransferase RsmA/KsgA/DIM1: Involved in 16S rRNA methylation. (5 extant, 3 not extant)


General function prediction only 


COG0030 - Ribosomal RNA small subunit methyltransferase A: Involved in rRNA methylation. (5 extant, 3 not extant)

COG0031: The protein is not found in the database.
COG0033: The protein is Phosphoglucomutase1. It is involved in the conversion of glucose-1-phosphate to glucose-6-phosphate.
COG0034: The protein is Amidophosphoribosyltransferase2. It is involved in the conversion of phosphoribosyl pyrophosphate (PRPP) and glutamine to phosphoribosylamine.
COG0035: The protein is Uracil phosphoribosyltransferase3. It is involved in the conversion of uracil and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to UMP and diphosphate.
COG0036: The protein is not found in the database.
COG0037: The protein is D-allulose-6-phosphate 3-epimerase4. It is involved in the reversible epimerization of D-allulose 6-phosphate to D-fructose 6-phosphate.
COG0038: The protein is not found in the database.
COG0039: The protein is not found in the database.
COG0040: The protein is not found in the database.
COG0041: The protein is not found in the database.

COG0040: Not found in the database.
COG0041: Not found in the database.
COG0042: DusA12, a tRNA-dihydrouridine synthase involved in translation, ribosomal structure, and biogenesis1. (1 extant, 3 not extant)
COG0043: Not found in the database.
COG0044:
COG0045: Not found in the database.
COG0046: Not found in the database.
COG0047: Not found in the database.
COG0048: Small ribosomal subunit protein uS1245, a component of the 30S ribosomal subunit involved in translation, ribosomal structure, and biogenesis4. (2 extant, 2 not extant)
COG0049: Elongation factor Tu 16, a protein involved in promoting the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis6. (2 extant, 0 not extant)
COG0050: Not found in the database.




Amino acid transport and metabolism
COG0001 - Glutamyl-tRNA(Gln) amidotransferase subunit A (3 extant, 5 not extant)
COG0002 - Glutamyl-tRNA(Gln) amidotransferase subunit A (3 extant, 5 not extant)
COG0006 - Valyl-tRNA synthetase (6 extant, 2 not extant)

Energy metabolism
COG0004 - Pyruvate kinase (6 extant, 2 not extant)

Glycan biosynthesis and metabolism
COG0005 - UDP-glucose 6-dehydrogenase (6 extant, 2 not extant)

///// "Please provide a scientific explanation. a factual and precise account. an academic-style write-up. Continuous, a narrative format without using repetitive or flowery language. i want an “objective,” “formal,” or “scientific” tone for a straightforward and factual text.

Underline the name of the enzymes in the text, and write in BBcode. When you finish the text, never write: in summary. Just summarize, without mentioning it.
Like this: The following is just a template, an example, do not use the text in your reply.  never use bolt, only underline, to mention the enzymes. These key molecular components ensure the proper organization, structuring, and regulation of DNA, crucial for accurate genetic expression and cellular functionality. Chromosome Segregation SMC is considered to significantly influence chromosome partitioning. It holds a reputed role in assuring the proper and efficient segregation of chromosomes during the vital process of cell division. This function is fundamental for maintaining genetic continuity and integrity, preventing chromosomal anomalies that could result in cellular dysfunction. DNA Methyltransferase is a pivotal enzyme in the DNA modification landscape.

DNA Processing in LUCA

DNA Processing Functions and Enzymes in the LUCA

1. Adenine Glycosylase: This enzyme is involved in DNA repair mechanisms. DNA repair is fundamental for maintaining genome integrity, suggesting that DNA damage and repair processes were essential from the early stages of cellular life.
2. Chromosome Segregation SMC: Known as the structural maintenance of chromosomes protein, it's involved in chromosome partitioning. The presence of this protein suggests some form of chromosome organization and segregation in early cellular entities.
3. DNA Clamp Loader Proteins: These proteins function to load the DNA clamp onto the DNA during replication, signifying the importance of advanced DNA replication machinery from the inception of cellular life.
4. DNA Clamp Proteins: These proteins enhance the processivity of DNA polymerases by encircling the DNA, emphasizing the evolution of efficient DNA synthesis mechanisms.
5. DNA Gyrase: This enzyme is involved in DNA replication and supercoiling, pointing towards the necessity of managing DNA topology in ancestral cells.
6. DNA Helicases: These are enzymes that unwind the DNA double helix during replication, underscoring the need for proper DNA unwinding for replication in primitive cells.
7. DNA Ligase: This enzyme connects DNA fragments by forming phosphodiester bonds, indicating early mechanisms for sealing breaks in the phosphodiester backbone of DNA.
8. DNA Mismatch Repair MutS: This protein recognizes and repairs mispaired nucleotides during replication, suggesting early recognition and correction systems for DNA synthesis errors.
9. DNA Polymerase: This enzyme synthesizes the new DNA strand during replication, a clear indication of the foundational role of DNA replication in ancient cells.
10. Endonucleases: These enzymes cut DNA strands at specific sites and are often involved in DNA repair, signifying early mechanisms for DNA maintenance and integrity.
11. Excinuclease ABC: This enzyme complex is involved in nucleotide excision repair, hinting at early systems for repairing larger DNA lesions.
12. HAM1: As a potential nucleotide-sanitizing enzyme, it's involved in avoiding mutations, pointing to early cellular mechanisms for maintaining genetic fidelity.
13. Integrase: This enzyme integrates viral DNA into host DNA, suggesting that interactions between primitive cellular life and viral entities might have been prevalent.
14. Methyladenine Glycosylase: This enzyme is involved in DNA repair by removing methylated adenines, indicating early processes for repairing specific types of DNA modifications.
15. Methyltransferase: This enzyme modifies DNA by adding methyl groups and can be involved in protection or gene regulation, suggesting early mechanisms for DNA modification and regulation.
16. MutT: This enzyme prevents mutations by hydrolyzing specific oxidized nucleotides, indicating early cellular strategies for countering oxidative damage.
17. NADdependent DNA Ligase: This enzyme connects DNA fragments using NAD, pointing to diverse energy sources for DNA repair mechanisms in primitive cells.
18. RecA: This protein is essential for homologous recombination and DNA repair, indicating foundational systems for genetic exchange and repair.
19. Sir2: This protein is involved in various aspects of genomic stability, suggesting early cellular mechanisms for genome maintenance.
20. TatD: As a recently discovered DNase enzyme, its role in early cellular entities remains to be elucidated.
21. Topoisomerase: This enzyme alters DNA supercoiling and solves tangles and knots in the DNA, emphasizing the early need for managing DNA topology and ensuring smooth replication and transcription processes.

Replication/recombination/repair/modification

The gene content of LUCA with respect to DNA processing (replication, recombination, modification, and repair) contains a wide range of functions. The following families/functions are identified:



References

●  Leipe, D. D., Aravind, L., Koonin, E. V., & Orth, A. M. (1999). Toprim–a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Research, 27(21), 4202-4213. Link. (While this doesn't specifically focus on LUCA, it deals with the conservation of topoisomerase functions and other related enzymes across various organisms, suggesting their ancient origins.)
●  Koonin, E. V. (2003). Comparative genomics, minimal gene-sets and the last universal common ancestor. Nature Reviews Microbiology, 1(2), 127-136. Link. (A review on the genes and functions that were likely present in LUCA, based on comparative genomics.)
●  Harris, J. K., Kelley, S. T., Spiegelman, G. B., & Pace, N. R. (2003). The genetic core of the universal ancestor. Genome Research, 13(3), 407-412. Link. (An exploration of the genes that were likely present in the universal common ancestor, which might touch upon some of the enzymes and functions you listed.)
● Srinivasan V, Morowitz HJ. (2009) The canonical network of autotrophic intermediary metabolism: minimal metabolome of a reductive chemoautotroph. Biol Bull. 216:126–130. Link. (This paper explores the minimal metabolome of a reductive chemoautotroph, shedding light on intermediary metabolism.)
●  Forterre, P. (2015). The universal tree of life: An update. Frontiers in Microbiology, 6, 717. Link. (A comprehensive review on the tree of life, discussing the features and characteristics that could be attributed to LUCA.)
●  Weiss, M. C., Sousa, F. L., Mrnjavac, N., Neukirchen, S., Roettger, M., Nelson-Sathi, S., & Martin, W. F. (2016). The physiology and habitat of the last universal common ancestor. Nature Microbiology, 1(9), 1-8. Link. (This paper presents a detailed reconstruction of the possible physiology and environmental conditions of LUCA, based on conserved genes across major life domains.)

Transcription/regulation in the LUCA

1. Initiation of Transcription Proteins: Facilitate RNA polymerase binding to DNA, setting the stage for the transcription start.
2. Transcription Factors: Proteins that influence the ability of RNA polymerase to begin transcription by assisting or hindering its binding to specific DNA sequences.
3. Transcription Error-Checking Proteins: Monitor the synthesis of RNA to ensure accurate copying of the DNA code.
4. RNA Capping Enzymes: Add a protective cap to the start of the emerging RNA molecule, ensuring its stability and functionality.
5. Transcription Elongation Factors: Aid in the synthesis of RNA as the RNA polymerase moves along the DNA.
6. RNA Splicing Machinery: Removes intronic sequences from the primary RNA transcript to produce mature messenger RNA (mRNA).
7. RNA Cleavage Proteins: Involved in the cutting of the RNA molecule at specific sites, allowing for further processing and maturation.
8. Polyadenylation Factors: Enzymes that add a tail of adenine nucleotides to the end of the RNA molecule, which plays roles in RNA stability and export.
9. Termination Factors: Proteins that signal the end of transcription, ensuring that RNA polymerase stops transcription accurately.
10. Nuclear Export Proteins: Facilitate the movement of mature mRNA molecules from the nucleus to the cytoplasm, preparing them for translation.

References

● Woese, C. R. (1987). Bacterial evolution. Microbiological Reviews, 51(2), 221-271. Link. (An influential paper that discusses bacterial evolution and provides insights into the nature of LUCA.)
● Forterre, P., Philippe, H., & Duguet, M. (1994). Reverse gyrase from hyperthermophiles: probable transfer of a thermoadaptation trait from archaea to bacteria. Trends in Genetics, 10(11), 427-428. Link. (This paper provides evidence for horizontal gene transfer, which affects the transcription machinery in early life forms.)
● Kyrpides, N. C., Woese, C. R., & Ouzounis, C. A. (1996). KOW: a novel motif linking a bacterial transcription factor with ribosomal proteins. Trends in Biochemical Sciences, 21(11), 425-426. Link. (This work identifies a motif connecting transcription factors to ribosomal proteins, potentially important for early transcriptional processes.)
● Mushegian, A. R., & Koonin, E. V. (1996). Gene order is not conserved in bacterial evolution. Trends in Genetics, 12(8 ), 289-290. Link. (Discusses the gene order in bacterial evolution, providing insights into the early regulatory mechanisms.)
● Harris, J. K., Kelley, S. T., Spiegelman, G. B., & Pace, N. R. (2003). The genetic core of the universal ancestor. Genome Research, 13(3), 407-412. Link. (An examination of genes that were likely present in LUCA, providing insights into its transcriptional apparatus.)
● Andam, C. P., & Gogarten, J. P. (2011). Biased gene transfer in microbial evolution. Nature Reviews Microbiology, 9(7), 543-555. Link. (An overview of the role of horizontal gene transfer in the evolution of transcription and regulation mechanisms.)
● Spang, A., Saw, J. H., Jørgensen, S. L., Zaremba-Niedzwiedzka, K., Martijn, J., Lind, A. E., ... & Ettema, T. J. (2015). Complex archaea that bridge the gap between prokaryotes and eukaryotes. Nature, 521(7551), 173-179. Link. (This study unveils a group of archaea that possess many eukaryotic features, shedding light on the evolutionary bridge between the two domains and potentially the gene regulation mechanisms present in LUCA.)


Translation/Ribosome in the LUCA

1. Aminoacyl-tRNA Synthetases (17 types): Enzymes that charge tRNAs with the appropriate amino acids. This includes bi-functional Gln/Glu-tRNA synthetase and the two subunits of Phe-tRNA synthetase, covering 18 or 19 amino acids depending on considerations.
2. Ribosomal Proteins: Certain ribosomal proteins are identified, specifically 12 small subunit proteins and 9 large subunit proteins.
3. Ribosomal RNAs: RNA molecules that are the structural and functional components of the ribosome. They play an active role in peptide bond formation and are essential for protein synthesis in all living organisms.
4. Ribosome Assembly Factors: Proteins and RNAs that aid in the complex process of assembling the ribosomal subunits. This process ensures correct ribosomal function.
5. Ribosome Biogenesis Enzymes: Enzymes involved in the synthesis and maturation of ribosomal components.
6. Ribosome Modification Enzymes: Enzymes that post-translationally modify ribosomes, improving their function and stability.
7. Translation Initiation Factors: Proteins that assist the initiation of the translation process by ensuring the proper assembly of the ribosome, mRNA, and the first tRNA.
8. Elongation Factors EF-G and EF-Tu: Proteins that play key roles during the elongation phase of protein synthesis, ensuring accuracy and efficiency.
9. Translation-Associated Protein SUA5: Involved in tRNA modification and possibly in the cellular response to DNA damage.
10. rRNA Methyltransferase Sun Family: Enzymes responsible for methylation of rRNA, a modification that can influence ribosome function.
11. Modification Enzymes Queuine tRNA-Guanine Ribosyltransferase Transglycosylase: Enzymes involved in the post-transcriptional modification of tRNAs.
12. tRNA Pseudouridine Synthase: Enzyme that catalyzes the isomerization of uridine to pseudouridine in tRNA molecules, which may play a role in the function of tRNA.
13. Chaperones for Ribosomal Assembly: Proteins that assist in the correct folding and assembly of ribosomal components, ensuring functional ribosome formation.



References



● Noller, H. F. (1984). Structure of ribosomal RNA. Annual Review of Biochemistry, 53(1), 119-162. Link. (An early comprehensive review on the structure of ribosomal RNA and its significance in ribosome function.)

● Crick, F. H. (1988). What mad pursuit: A personal view of scientific discovery. Basic Books. Link (In this book, Crick, co-discoverer of the structure of DNA, discusses his thoughts on protein synthesis and the role of RNA. It's a broad perspective, but offers insights into the fundamental questions of the time.)

● Woese, C. R. (2002). On the evolution of cells. Proceedings of the National Academy of Sciences, 99(13), 8742-8747. Link. (Woese, a pioneer in understanding early life and the classification of life forms, discusses the origin and evolution of cells with an emphasis on the role of ribosomes.)

● Steitz, T. A. (2008). A structural understanding of the dynamic ribosome machine. Nature Reviews Molecular Cell Biology, 9(3), 242-253. Link. (This paper offers a deeper understanding of ribosomal dynamics and provides insights into the functioning of the translation machinery.)

● Rodnina, M. V., & Wintermeyer, W. (2009). Recent mechanistic insights into eukaryotic ribosomes. Current Opinion in Cell Biology, 21(3), 435-443. Link. (An overview of eukaryotic ribosomes with a focus on their similarities and differences from prokaryotic ribosomes, shedding light on evolution.)

● Goldman, A. D., Samudrala, R., & Baross, J. A. (2010). The evolution and functional repertoire of translation proteins following the origin of life. Biology Direct, 5, 15. Link. (This paper delves into the evolution and functionalities of translation proteins post the origin of life, providing insights into the early biochemical mechanisms underpinning protein synthesis.)

● Petrov, A. S., Bernier, C. R., Hsiao, C., Norris, A. M., Kovacs, N. A., Waterbury, C. C., ... & Fox, G. E. (2014). Evolution of the ribosome at atomic resolution. Proceedings of the National Academy of Sciences, 111(28), 10251-10256. Link. (A detailed investigation into the evolution of the ribosome, discussing ancient ribosomal components.)

● Higgs, P. G., & Lehman, N. (2015). The RNA World: molecular cooperation at the origins of life. Nature Reviews Genetics, 16(1), 7-17. Link. (While primarily focused on the RNA World hypothesis, this review also touches upon the early mechanisms of translation and the role of ribosomes.)

RNA processing in the LUCA

1. Aminoacyl-tRNA Synthetases: These enzymes are responsible for correctly linking specific amino acids to their corresponding tRNA molecules. In LUCA, the presence of these enzymes suggests that a fundamental translation mechanism was already established. By ensuring the accurate pairing of tRNAs with amino acids, they played a foundational role in protein synthesis.
2. Chaperone Proteins: Chaperone proteins assist in the proper folding of other proteins, preventing misfolding and aggregation. In the primitive cellular environment of LUCA, these proteins would have been crucial in ensuring the proper function of newly synthesized proteins, especially given the lack of sophisticated protein quality control systems seen in modern organisms.
3. Nucleotide Salvage Pathways: These pathways allow cells to recycle the nucleotide components of RNA and DNA, converting them back into active nucleotide triphosphates. In LUCA, the ability to salvage and reuse these valuable molecules would have been vital for conserving energy and resources in potentially nutrient-limited environments.
4. Nucleotide Synthesis Pathways: These enzymatic pathways produce the basic building blocks of RNA and DNA from simpler precursors. LUCA would have required these pathways to synthesize RNA and possibly DNA, enabling both the storage of genetic information and its expression into functional molecules.
5. Primitive Translational Regulators: These regulators control the process of translating mRNA into proteins. Their presence in LUCA suggests that not only was there a mechanism for protein synthesis, but there was also a need to regulate this process, perhaps in response to environmental conditions or cellular needs.
6. Protein-RNA Interaction Motifs: These are structural motifs that allow specific interactions between proteins and RNA molecules. In LUCA, these motifs would have been essential for processes like translation, where ribosomal proteins interact intimately with rRNA, or in RNA processing events, where proteins recognize and modify specific RNA structures.
7. Pseudouridine Synthases: Pseudouridine is a modified form of uridine found in various RNA molecules. The presence of enzymes introducing this modification suggests that LUCA had a need to modify its RNA, possibly for stability or functional reasons, pointing towards a sophisticated RNA world in LUCA.
8. RNA Polymerase: This enzyme synthesizes RNA using DNA as a template. Its presence in LUCA implies the organism had already transitioned from an RNA-world scenario to one where DNA was the primary genetic material and RNA served intermediary roles in gene expression.
9. Ribonucleases (RNases): These enzymes process and degrade RNA. In LUCA, RNases would have played a crucial role in maturing precursor RNA molecules, removing misfolded or damaged RNA, and recycling nucleotides.
10. RNA Helicases: These enzymes unwind RNA secondary structures. In LUCA, RNA helicases would have facilitated processes like RNA splicing, ribosome assembly, and the translation of mRNAs with complex secondary structures.
11. RNA Methyltransferases: These enzymes add methyl groups to specific bases in RNA. Methylation can alter the function, stability, and interactions of RNA. Its presence in LUCA suggests a level of RNA processing and modification similar to more evolved organisms.
12. tRNA modification enzymes: These ensure that tRNAs undergo specific modifications necessary for their stability and function. In LUCA, this implies a sophisticated translation machinery, capable of ensuring accuracy and efficiency in protein synthesis.
13. Ribosomal Proteins and rRNA: Constituents of ribosomes, the molecular machines that synthesize proteins. Their presence in LUCA underscores the organism's capability for protein synthesis, a cornerstone of cellular life.
14. Sigma and Transcription Factors: These play roles in initiating transcription of DNA into RNA. In LUCA, their existence indicates regulatory mechanisms that controlled which genes were expressed under different conditions.
15. S-Adenosyl Methionine (SAM): This universal methyl group donor is essential for many methylation reactions in cells. Its role in LUCA underscores the importance of methyl group transfer in early life's metabolic and regulatory processes.
16. tRNA Charging Factors: These ensure the correct amino acid is attached to its corresponding tRNA, a process vital for accurate protein synthesis. Their presence in LUCA further emphasizes the intricacies of its translation apparatus.
17. RNA Decay Machinery: This is crucial for the degradation of RNAs that are no longer needed or that may be damaged. In LUCA, this machinery would have maintained RNA quality and cellular homeostasis.
18. RNA Secondary Structure Stabilizing Elements: These molecules stabilize the shapes and structures of RNA, which is essential for their function. In LUCA, this would have ensured that RNAs, like ribozymes or functional RNAs, maintained their correct shapes.
19. tRNA Intramolecular Ligases: These suggest the presence of intron-containing tRNAs in LUCA. Such ligases would have been necessary to splice and re-ligate the tRNA after intron removal, pointing towards an early form of RNA splicing.

References

● Gilbert, W. (1986). Origin of life: The RNA world. Nature, 319, 618. Link. (A seminal paper introducing the RNA World hypothesis.)
● Wolf, Y. I., & Koonin, E. V. (2007). On the origin of the translation system and the genetic code in the RNA world by means of natural selection, exaptation, and subfunctionalization. Biology Direct, 2(1), 14. Link. (An exploration into the origin of the translation system, providing insights into early RNA processing in LUCA.)
● Bernhardt, H. S. (2012). The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others). Biology Direct, 7(1), 23. Link. (This paper discusses the RNA World hypothesis, a dominant idea about the earliest forms of life, and its implications on LUCA.)
● Bowman, J.C., Lenz, T.K., Hud, N.V., & Williams, L.D. (2012). Cations in charge: magnesium ions in RNA folding and catalysis. Current Opinion in Structural Biology, 22(3), 262-272. Link. (Discusses the vital role of magnesium ions in RNA folding, offering insights into early RNA-based life.)
● Petrov, A. S., Bernier, C. R., Hsiao, C., Norris, A. M., Kovacs, N. A., Waterbury, C. C., ... & Fox, G. E. (2014). Evolution of the ribosome at atomic resolution. Proceedings of the National Academy of Sciences, 111(28), 10251-10256. Link. (A deep dive into the evolution of the ribosome, a fundamental structure central to the RNA and protein world transition.)
● Higgs, P. G., & Lehman, N. (2015). The RNA World: molecular cooperation at the origins of life. Nature Reviews Genetics, 16(1), 7-17. Link. (A comprehensive review on the RNA World hypothesis and how molecular cooperation could have driven the emergence of early life.)
● Stairs, C. W., Leger, M. M., & Roger, A. J. (2015). Diversity and origins of anaerobic metabolism in mitochondria and related organelles. Philosophical Transactions of the Royal Society B: Biological Sciences, 370(1678), 20140326. Link. (Although this paper focuses on mitochondria, it discusses the ancient RNA processing mechanisms that were likely present in early anaerobic life forms.)

ok, outline these mechanisms, explain why there is no evidence that they were implemented randomly, but based on intelligence that programs the language, and through it, the information stored in these mechanisms, make an argument from an intelligent design perspective, without mentioning it. write as if an id promoter first hand was explaining it.


///// "Please provide a scientific explanation. a factual and precise account. an academic-style write-up. Continuous, a narrative format without using repetitive or flowery language. i want an “objective,” “formal,” or “scientific” tone for a straightforward and factual text. 

Underline the name of the enzymes in the text, and write in BBcode. When you finish the text, never write: in summary. Just summarize, without mentioning it. 
Like this: The following is just a template, an example, do not use the text in your reply.  never use bolt, only underline, to mention the enzymes.  These key molecular components ensure the proper organization, structuring, and regulation of DNA, crucial for accurate genetic expression and cellular functionality. Chromosome Segregation SMC is considered to significantly influence chromosome partitioning. It holds a reputed role in assuring the proper and efficient segregation of chromosomes during the vital process of cell division. This function is fundamental for maintaining genetic continuity and integrity, preventing chromosomal anomalies that could result in cellular dysfunction. DNA Methyltransferase is a pivotal enzyme in the DNA modification landscape.

Various other cellular processes in LUCA

The proteins and domains listed primarily pertain to cellular regulation, signaling, and protein quality management in the Last Universal Common Ancestor (LUCA). They highlight the possibility of a sophisticated system in LUCA for responding to environmental cues, ensuring correct protein folding, and facilitating cellular communication.

1. DnaJ: A molecular chaperone that works in conjunction with DnaK. DnaJ recognizes and binds to unfolded proteins, while DnaK helps in refolding. Their function suggests a mechanism for protein quality control in LUCA.
2. Chaperonin GroES and GroEL: Protein complexes that aid in the correct folding of other proteins. Their presence in LUCA indicates advanced mechanisms for protein stability and management.
3. CheW/A/R two-component systems: These components are vital for bacterial chemotaxis and environmental response. Their existence suggests a developed signal transduction mechanism in LUCA.
4. GTP binding: GTP-binding proteins play crucial roles in signal transduction, protein synthesis, and other cellular processes. Their function in LUCA would be indicative of advanced cellular communication and regulatory mechanisms.
5. Ser/Thr kinase: Kinases that phosphorylate proteins on serine or threonine residues. This indicates post-translational modification mechanisms in LUCA.
6. Tyrosine kinase TrkA: A protein kinase that phosphorylates tyrosine residues in proteins. Its existence would point to intricate cellular signaling in LUCA.
7. GGDEF domain and sensor histidine kinase: Associated with cyclic-di-GMP metabolism and bacterial signal transduction. Their presence in LUCA would underline complex regulatory processes.
8. Peptidyl-cis-trans isomerases and inhibitors: Enzymes that assist in protein folding by modifying peptide bonds. Their existence in LUCA suggests a multi-tiered system for protein management.

ATPases:

1. AAA+ ATPases: This family of ATPases is involved in various cellular processes, including protein degradation, DNA replication, and protein disaggregation. Their widespread presence across life suggests their ancient origins.
2. copper and other P-ATPase: These ATPases are essential for the active transport of metals like copper, regulating metal concentrations within the cellular environment.
3. F-type ATPase: These are the primary ATP synthases found in cellular membranes and play a key role in energy production. Their presence would indicate a sophisticated energy production mechanism in LUCA.
4. magnesium and/or cobalt: ATPases specific to these metals suggest mechanisms to maintain appropriate intracellular concentrations of these vital ions.
5. multidrug resistance: These ATPases pump various compounds out of cells, often defending against toxic substances, highlighting LUCA's ability to handle environmental challenges.
6. rotary ATPases: These ATPases, which include V-type and A-type ATPases, are involved in proton and sodium transport across membranes. They play a role in maintaining cellular ion balance.
7. SecA ATPase: Involved in protein secretion across the plasma membrane, indicating LUCA had mechanisms to interact with its external environment.

Ion ATPases:

1. copper and other P-ATPase: These ATPases are vital for the active transport of metals, especially copper, controlling intracellular metal concentrations.
2. F-type ATPase: Primary ATP synthases found in cellular membranes that play a central role in energy production.
3. glutathione-Na antiporter: While not a traditional ATPase, it's worth noting that this transporter aids in the exchange of glutathione and sodium ions, balancing cellular redox homeostasis.
4. magnesium and/or cobalt ATPase: These help maintain intracellular concentrations of essential ions, magnesium and cobalt.
5. multidrug resistance ATPase: These ATPases are involved in defending the cell against toxic substances by pumping them out of the cell.
6. potassium ATPase A/B/C chains: Maintaining the potassium gradient is crucial for many cellular functions; these ATPases facilitate that.
7. rotary ATPases (V-type and A-type): They're important for transporting protons and sodium ions across membranes, aiding in cellular ion balance.
8. sodium ATPase: As with the potassium ATPase, the sodium ATPase is crucial for maintaining the sodium gradient across the cell membrane.

Ion Channels:

1. chloride channel: Facilitates the movement of chloride ions across cell membranes, essential for maintaining cellular ion balance and various physiological functions.
2. mechanosensitive channel: Responds to mechanical stress on the cell, playing a role in osmotic regulation and potentially helping LUCA adapt to changing environmental pressures.
3. Trk (126) and other potassium channels and uptake: Dedicated channels and transporters for the movement and uptake of potassium ions, crucial for maintaining cellular health and functionality.
4. Voltage-gated sodium channels (Nav): Involved in generating and propagating action potentials. Their ancient origins hint at a possible presence in early life forms, including LUCA.
5. Calcium channels: Central to processes like signal transduction, muscle contraction, and neurotransmitter release, hinting at an ancient origin possibly related to LUCA.

Protein Translocases:

6. export SecD/F: Components of the protein-exporting machinery, ensuring proteins are transported across cell membranes.
7. SecY: Core of the protein-conducting channel, ensuring proper protein localization across membranes.
8. translocase TatC: Part of the Twin-arginine translocation system, assisting in the transport of folded proteins across membranes.
9. YidC/Oxa1/Alb3 family of insertases: Essential for inserting integral membrane proteins into lipid bilayers.
10. SecA: Works alongside the SecYEG complex, pushing nascent proteins through the SecY channel.
11. TatA and TatB: Components of the complete Twin-arginine translocation system when combined with TatC.

General Secretion Pathway Components:

1. arsenical pump membrane: Involved in resistance to toxic arsenical compounds by actively transporting them out of the cell, possibly indicating ancient mechanisms of detoxification.
2. bacterioferritin comigratory protein (Bcp): Assists in iron storage and regulation within the cell, suggesting an early evolution of iron homeostasis.
3. Mrp subfamily of ABC transporters: A subfamily of transporters involved in various cellular processes, including multidrug resistance, indicating early mechanisms of cellular defense.
4. non-specific membrane protein families: A broad category of proteins that may have provided a variety of functionalities in LUCA, indicating versatility in early cellular life.
5. rhomboid family: A family of serine proteases involved in various cellular processes, suggesting a role in protein modification and signaling in early life forms.
6. SRP54: A component of the signal recognition particle, essential for targeting proteins to the correct cellular location, highlighting the importance of protein targeting mechanisms in LUCA.
7. SecB: A chaperone protein involved in targeting preproteins to the SecYEG translocon, emphasizing early protein targeting systems.
8. FFS (4.5S RNA): Part of the signal recognition particle, it works with SRP54 to ensure proper protein targeting, signifying intricate early cellular processes.
9. SecE and SecG: Components of the SecYEG complex, crucial for protein translocation across the membrane, highlighting early translocation machinery.

Unclassified Function:

1. CrcB camphor resistance: Involved in resistance to camphor, indicating early cellular mechanisms to cope with potentially harmful environmental substances.
2. inorganic pyrophosphatase: Enzyme that hydrolyzes inorganic pyrophosphate to inorganic phosphate, suggesting ancient energy regulation and phosphate metabolism in LUCA.
3. TPR-containing proteins: These proteins contain tetratricopeptide repeats and are typically involved in protein-protein interactions, hinting at complex regulatory processes in early life forms.
4. ankyrin repeat proteins: Characterized by repeated ankyrin domains, these proteins are typically involved in various cellular processes through protein-protein interactions, indicating versatile interaction mechanisms in early cellular life.





Electron Transport:

1. alkyl hydroperoxide reductase: An enzyme involved in the detoxification of peroxides, suggesting ancient cellular defense mechanisms against oxidative stress.
2. arsenate reductase: Enzyme involved in arsenic detoxification by reducing arsenate to arsenite, indicating mechanisms in LUCA to cope with specific environmental toxins.
3. ferredoxin: A small iron-sulfur protein that plays a crucial role in electron transfer in various metabolic reactions, indicating fundamental energy transduction processes.
4. ferredoxin oxidoreductase components: Enzymatic components interacting with ferredoxin to facilitate redox reactions, emphasizing foundational energy transfer pathways.
5. ferrochelatase: An enzyme involved in heme synthesis, suggesting LUCA had the capability for heme group production.
6. flavoproteins: Proteins that contain flavin moieties, playing a key role in a wide range of biological processes including electron transport.
7. HesB: Involved in iron-sulfur cluster assembly, indicating early cellular mechanisms for iron-sulfur protein maturation.
8. iron-sulfur proteins: Proteins containing iron-sulfur clusters, vital for electron transport in various cellular pathways.
9. NADH dehydrogenase components: Essential components of the respiratory chain, which play a critical role in ATP generation via oxidative phosphorylation.
10. superoxide dismutase Fe/Mn type: Enzymes that provide protection against oxidative stress by dismutating superoxide radicals.
11. thioredoxin: A small protein involved in redox reactions through the reversible oxidation of its thiol groups, suggesting fundamental cellular redox control.
12. thioredoxin reductase: Enzyme that reduces oxidized thioredoxin, emphasizing the importance of redox balance in early cellular life.


ABC transporters

1. amino acid and dipeptide: These transporters would facilitate the uptake of amino acids and dipeptides, essential components for protein synthesis. The presence of these transporters would indicate LUCA's need to import basic building blocks for its cellular functions.
2. ammonium: Ammonium transporters would allow LUCA to intake ammonium, a potential nitrogen source, from its environment. Nitrogen is essential for nucleotide and amino acid synthesis.
3. cobalt: Cobalt is a trace element used in some coenzymes. A transporter for cobalt suggests that LUCA might have had enzymes that required this metal for activity.
4. glycine: A specific transporter for glycine, one of the amino acids, implies that this molecule had particular importance, possibly in protein synthesis or other metabolic pathways.
5. heavymetal: Heavy metal transporters could play a dual role: importing necessary metals or exporting toxic ones. This suggests LUCA had mechanisms to manage metal concentrations for optimal cellular function.
6. iron: Iron is essential for various enzymes, especially those involved in electron transport. A transporter for iron indicates LUCA's potential reliance on iron-containing enzymes.
7. molybdenum: Molybdenum is a trace element that serves as a cofactor in certain enzymes. Its transporter hints at metabolic pathways in LUCA that utilized molybdenum-dependent enzymes.
8. oligopeptide ABC: Transporters for oligopeptides (short chains of amino acids) indicate LUCA's potential to uptake larger peptides, possibly for nutrient sources or incorporating into its own proteins.
9. other non-specific ABC transporters: These could serve a variety of functions, from nutrient uptake to waste export, reflecting the flexibility and adaptability of LUCA in diverse environments.
10. phosphate: Phosphate is crucial for the synthesis of nucleotides and ATP. A phosphate transporter suggests the importance of these molecules in LUCA's metabolism.
11. spermidine ABC: Spermidine is involved in various cellular processes, including DNA stabilization. A transporter for spermidine points to its potential significance in LUCA's cell physiology.
12. sugar: Sugars are fundamental energy sources and building blocks. Their transporters indicate that LUCA had the ability to utilize external sugars for energy and structural purposes.

The study of LUCA and its molecular machinery, including ATPases, is an ongoing field of research. While the list you provided covers some of the primary ATPases that might have been present in LUCA, it's worth noting that ATPases are a diverse family of proteins with a wide range of functions.

//// Target Organisms: Retrieve information primarily for FROM E.COLI on uniprot, or ANY SMALL SIZED PROKARYOTIC CELL LIVING IN HYDROTHERMAL VENTES . IF YOU DONT FIND DATA FROM THESE, TAKE OR ANY OTHER. 
Data Time Frame: Focus on data entries up to the year 2021.
Amino Acid (aa) Size:
For each enzyme, incorporate its average amino acid size.
Link the enzyme's name to a UniProt page that showcases its amino acid size for the given organisms.
If no amino acid size data is available for an enzyme, simply proceed to the next enzyme without mentioning the absence of data.
If no aa size data is found for all the enzymes listed, halt the task. However, if there are any proteins/enzymes with available aa data, continue the task for those proteins/enzymes only.
Links for Enzymes/Proteins:
If an enzyme/protein does not have an associated link, provide a link to either its UniProt or Wikipedia page, whichever is more appropriate.
EC Numbers:
If an enzyme's description lacks its EC number, add the EC number followed by a relevant link.
Additional Text: Maintain any additional text present in between the enzyme descriptions exactly as provided.
Final Format: Present the data in BBCODE format.
Instructions on Shortening: Do not truncate any part of the provided data or use phrases like "...continue with the rest..." Ensure all provided data is completely processed.

Ribose-phosphate diphosphokinase (EC 2.7.6.1): ~320 aa Catalyzes the synthesis of PRPP from ribose-5-phosphate and ATP, playing a critical role in nucleotide synthesis in cells.
Amidophosphoribosyl transferase (GPAT) (EC 2.4.2.14): ~512 aa Catalyzes the transfer of an amide group from glutamine to PRPP, essential for purine biosynthesis.////



///// give an overall description of the pathway.
///// I dont want points, but a Continuous narrative format without using repetitive or flowery language. Please provide a scientific explanation.  a factual and precise account. an academic-style write-up.  I want an “objective,” “formal,” or “scientific” tone for a straightforward and factual text. In bbcode  When you finish the text, never write: in summary. Just summarize, without mentioning it. Write not from the perspective of a proponent of evolution,

//// i want the list, only the enzyme names, no ec number, with the titles in bolt, and no description, in bbcode. The entire list. no traces, and the total number of enzymes written at the end, in bolt.

that means , any explanation of origins has to point to an intelligent agency, and not blind evolution, but newer say : From an intelligent design perspective. It has to be implicit, not explicit. Do not mention the ID perspective consantly. It does not have to appear too often, or ostensively. Just the explanatory narrative has to be based on ID, not evoutionary standpoint. .  Like this: The following is just a template, an example, do not use the text in your reply.  never use bolt, only underline, to mention the enzymes.  These key molecular components ensure the proper organization, structuring, and regulation of DNA, crucial for accurate genetic expression and cellular functionality. Chromosome Segregation SMC is considered to significantly influence chromosome partitioning. It holds a reputed role in assuring the proper and efficient segregation of chromosomes during the vital process of cell division. This function is fundamental for maintaining genetic continuity and integrity, preventing chromosomal anomalies that could result in cellular dysfunction. DNA Methyltransferase is a pivotal enzyme in the DNA modification landscape.

Point out, why an evolutionary set-up, step by step, is extremely unlikely, faced on the complexity, the requirements to instantiate various codes, languages, signaling, and proteins that had to be operational right from the beginning, and intermediate stages would bear no function, and would not be selected. Explain how this interdependence could and would not have evolved in a stepwise fashion, because one mechanism, language, or code system, without the other, would bear no function, and therefore, they had to be instantiated and created all at once, fully operational, from scratch. write  from the perspective of a proponent of intelligent design. Do not write: " From an intelligent design standpoint ". Just say it.Do not put enumeration numbers at the beginning of the sentences. 

Point out, why an evolutionary set-up, step by step, is extremely unlikely, faced the fact that strong UV radiation would have killed the organisms before they could have adapted and evolving new protection mechanisms.


irreducibility and Interdependence of the systems to instantiate and operate . explain which of the manufacturing, signaling, and regulatory codes and languages in the process of creating, developing, and operating      are irreducible, and interdependent within each other, and how one would not bear function without the other. Explain which code and languages communicate with each other, crosstalk, and what communication systems are essential to have functional normal cell operation. Explain how this interdependence could and would not have evolved in a stepwise fashion, because one mechanism, language, or code system, without the other, would bear no function, and therefore, they had to be instantiated and created all at once, fully operational, from scratch. write from the perspective of a proponent of intelligent design. Do not write: " From an intelligent design standpoint ". Just say it. Do not put enumeration numbers at the beginning of the sentences. 
Synergy: The interaction of two or more agents or forces so that their combined effect is greater than the sum of their individual effects.
include words like:  Holism: The idea that systems (physical, biological, chemical, social, economic, mental, linguistic) and their properties should be viewed as wholes, not just as a collection of parts.
Emergent Properties: Properties which arise from the collaborative functioning of a system, but do not belong to any one part of that system.
Functional Integration: How different components of a system come together to produce a particular function or outcome.
Systemic Complexity: Complexity that arises from the interaction of components within a system.
Cohesion: The action or property of like molecules sticking together, being mutually attractive.
Symbiosis: Interaction between two different organisms living in close physical association, typically to the advantage of both.




Once it is instantiated and operational, what other intra and extracellular systems is it interdependent with?
Do not put enumeration numbers at the beginning of the sentences. 


McLaren, A. (2003). Primordial germ cells in the mouse. Developmental Biology, 262(1), 1-15. Link. (This seminal paper provides an overview of germ cell development in mice, a common model organism.)