Prevital unguided origin of the four basic building blocks of life: Impossible !!

Prevital unguided origin of the four basic building blocks of life: Impossible !!

https://reasonandscience.catsboard.com/t2894-prevital-unguided-origin-of-the-four-basic-building-blocks-of-life-impossible

Steve Benner, leading origin of life researcher, prior Harvard University professor. Paradoxes in the origin of life. 2015 Jan 22 

" We are now 60 years into the modern era of prebiotic chemistry. That era has produced tens of thousands of papers attempting to define processes by which “molecules that look like biology” might arise from “molecules that do not look like biology” …. For the most part, these papers report “success” in the sense that those papers define the term…. And yet, the problem remains unsolved " 

http://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/25608919

Evidence points to the fact that none of the basice building blocks of life: 

1. Amino acids 
2. Nucleotides 
3. Carbohydrates  
4. phospholipids 

could have emerged by random unguided processes on early earth. 

Chemical evolution of amino acids and proteins ? Impossible !!
https://www.youtube.com/watch?v=1L1MfGrtk0A

The problem of getting nitrogen to make amino acids and DNA on early earth   2:41
The problem of getting all amino acids used in llife by origin of life experiments 4:20
The problem of selecting 20 amino acids prebiotically out of hundreds supposedly existing on early earth. 6:08
The problem of concentrating the amino acids used in life at one assembly site.  7:15
The problem of understanding why life uses 20 amino acids, and not more or less. 9:00
The problem of homochirality 12:23
The problem of amino acid synthesis regulation 13:43
The problem of peptide bonding of amino acids to form proteins 14:12
The problem of linking the right amino acid side sequence together  17:15  
The problem of getting the right forces to stabilize proteins - essential for their correct folding 19:32
The problem of hierarchical structures of proteins 19:50

RNA & DNA: It's prebiotic synthesis: Impossible !!
https://www.youtube.com/watch?v=-ZFlmL_BsXE

Genetic takeover, Cairns Smith, page 66:  
Now you may say that there are alternative ways of building up nucleotides, and perhaps there was some geochemical way on the early Earth. But what we know of the experimental difficulties in nucleotide synthesis speaks strongly against any such supposition. However it is to be put together, a nucleotide is too complex and metastable a molecule for there to be any reason to expect an easy synthesis.

Prebiotic synthesis of carbohydrates: Impossible !!

The ultimate origin of  Glucose - sugars is a huge problem for those who believe in life from non-life without requiring a creator.  In order to provide credible explanations of how life emerged, a crucial question must be answered : Where did Glucose come from in a prebiotic  earth ? The source of glucose and other sugars used in metabolic processes would have to lie in an energy-collecting process. Without some means to create such sugar, limitations of food supply for metabolic processes would make the origin of life probably impossible.

main unknown issue about the origin of life is to identify the first energy capture and carbon fixation mechanism used by the primitive organisms that populated the young biosphere. A prebiotic system should have also been able to implement the core reactions involved in central metabolism abiotically and nonenzymatically. One of them, the reverse TCA cycle is often proposed as the leading candidate to be the first carbon fixation mechanism. Sugars are versatile molecules, belonging to a general class of compounds known as carbohydrates, which serve a structural role as well as providing energy for the cell. Science today shifts its hope to find the solution of the riddle to hydrothermal vents because they are populated by chemoautotrophic bacterias, which use this alternative mechanism for Carbon fixation, namely the reverse Citric Acid Cycle, or tricarboxylic Cycle (TCA). The TCA is the central hub from which all basic building blocks for life are derived, by all three domains of life. So the origin of the TCA is a central OOL problem. The enzymes used in the cycle are:

1, malate dehydrogenase
2, fumarate hydratase (fumarase)
3, fumarate reductase
4, succinyl-CoA synthetase
5, 2-oxoglutarate:ferredoxin oxidoreductase
6, isocitrate dehydrogenase
7, aconitate hydratase (aconitase)
8, ATP citrate lyase
9, pyruvate:ferredoxin oxidoreductase   Fdred, reduced ferredoxin.

So the question is, how did a transition from a non-enzymatic, to an enzymatic production of fixed carbon occur? There is speculation, but no evidence exists that it is possible.

Prebiotic origin of cell membranes by natural means: Impossible !!

Some popularisers of abiogenesis like to draw diagrams showing a simple hollow sphere of lipid (a ‘vesicle’) that can form under certain conditions in a test-tube. However, such a ‘membrane’ could never lead to a living cell because the cell needs to get things through the cell membrane, in both directions. Such transport into and out of the cell entails very complex protein-lipid complexes known as transport channels, which operate like electro-mechanical pumps. They are specific to the various chemicals that must pass into and out of the cell (a pump that is designed to move water will not necessarily be suitable for pumping oil). Many of these pumps use energy compounds such as ATP to actively drive the movement against the natural gradient. Even when movement is with the gradient, from high to low concentration, it is still facilitated by carrier proteins.

Where did Glucose come from in a prebiotic world ?
https://reasonandscience.catsboard.com/t2419-where-did-glucose-come-from-in-a-prebiotic-world

RNA & DNA: It's prebiotic synthesis: Impossible !!
https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible

Chemical evolution of amino acids and proteins ? Impossible !!
https://reasonandscience.catsboard.com/t2887-chemical-evolution-of-amino-acids-and-proteins-impossible

Cell Membranes, origins through natural mechanisms, or design ?
http://reasonandscience.heavenforum.org/t2128-cell-membranes-origins-through-natural-mechanisms-or-design

The trajectory from a prebiotic synthesis of the basic building blocks of life, to the sophisticated synthesis by cell factories: an unsolved riddle


https://reasonandscience.catsboard.com/t2894-prevital-unguided-origin-of-the-four-basic-building-blocks-of-life-impossible#7650

402 individual reactions synthesize amino acids, nucleotides and cofactors from H2, CO2, NH3, H2S and phosphate in modern cells
https://www.frontiersin.org/articles/10.3389/fmicb.2021.793664/full%20?utm_source=fweb&utm_medium=nblog&utm_campaign=ba-sci-fmicb-luca-hydrothermal-vents-core-energy

We identified a set of roughly 400 ancient reactions that cells use to synthesize the 20 amino acids of proteins, the four bases of genes, and the 18 vitamins that cells need to make those 400 reactions work. Those core chemical reactions are conserved across all microbial lineages, hence they were present in the last universal common ancestor of all life, LUCA. They provide a window into the source of building blocks, but also the source of energy at origins.
https://blog.frontiersin.org/2022/01/19/frontiers-microbiology-origin-of-life-energy-hydrothermal-vents/

Marian Breuer Essential metabolism for a minimal cell Jan 18, 2019
Our model features 338 reactions organized in nine subsystems involving 304 metabolites, catalyzed by gene products of 155 genes, thus covering a third of the genes of JCVI-syn3A.
https://elifesciences.org/articles/36842

Modern cells use vast resources of information, basic elements of matter, and energy, to synthesize the four basic building blocks: 

1. Amino acids  
2. Nucleotides 
3. Carbohydrates  
4. phospholipids. 

These individual components are themselves complex, and very specific, and the cell machinery uses several highly sophisticated and controlled metabolic pathways to synthesize them, where both, anabolism, and catabolism play a role, that is, de-novo synthesis, and recycling. This requires a minimal genome, proteome, and metabolome. Sophisticated signaling networks are constantly in use to detect the required quantities based on the external availability of food and to maintain intracellular homeostasis.  Obviously, this ultrasophisticated chemical factory was not extant on the early earth. 

Modern abiogenesis research focusses on attempting to elucidate how these basic molecules could have emerged by chemical evolution on the early earth, prior to the emergence of the modern chemical cell factories that all life forms use. In almost 70 years, rather than making progress to solve the riddle, general frustration is the case. 

Steve Benner, one of the world’s leading authorities on abiogenesis, summed it up:
We are now 60 years into the modern era of prebiotic chemistry. That era has produced tens of thousands of papers attempting to define processes by which “molecules that look like biology” might arise from “molecules that do not look like biology” …. For the most part, these papers report “success” in the sense that those papers define the term…. And yet, the problem remains unsolved

In the following, I am outlining a MINIMAL number of enzymes involved in synthesizing these building blocks. Not taken into consideration, is all the machinery, that is involved synthesizing the co-factors, metal clusters, metal import channels, chaperones, etc. that are required to get functional proteins.   

Nucleotides
Folate is necessary for the production and maintenance of new cells, for DNA synthesis and RNA synthesis through methylation. The synthesis of NADPH requires six enzymes. 5 Six proteins are required in the folate pathway. 4 

RNA 
Nucleotides are building blocks for DNA and RNA. Three Pyrimidines and Two Purines Are Commonly Found in Cells.
The pyrimidine synthesis pathway requires six regulated steps, seven enzymes, and energy in the form of ATP.
The starting material for purine biosynthesis is Ribose 5-phosphate, a product of the highly complex pentose phosphate pathway, which uses 12 enzymes. 1 
De novo purine synthesis pathway requires ten regulated steps, eleven enzymes, and energy in the form of ATP. 

DNA
The replacement of RNA as the repository of genetic information by its more stable cousin, DNA, provides a more reliable way of transmitting information. DNA uses thymine (T) as one of its four informational bases, whereas RNA uses uracil (U). 
At the C2' position of ribose, an oxygen atom is removed. The remarkable enzymes that do this are named Ribonucleotide reductases (RNR).  The iron-dependent enzyme is essential for DNA synthesis, and most essential enzymes of life 32, and it has one of the most sophisticated allosteric regulations known today. 50 
The thymine-uracil exchange constitutes one of the major chemical differences between DNA and RNA. Before being incorporated into the chromosomes, this essential modification takes place. Uracil bases in RNA are transformed into thymine bases in DNA. The synthesis of thymine requires seven enzymes. De novo biosynthesis of thymine is an intricate and energetically expensive process. 
All in all, not considering the metabolic pathways and enzymes required to make the precursors to start RNA and DNA synthesis requires at least 26  enzymes.  

Amino Acids
Several classes of reactions play special roles in the biosynthesis of amino acids and nucleotides
(1) transamination reactions and other rearrangements promoted by enzymes containing pyridoxal phosphate (PLP), which requires eight enzymes to be synthesized. 3
(2) transfer of one-carbon groups, with either tetrahydrofolate or S-adenosylmethionine as a cofactor; tetrahydrofolate is derived from the folate pathway, 
(3) transfer of amino groups derived from the amide nitrogen of glutamine.

As implied by the root of the word (amine), the key atom in amino acid composition is nitrogen. All organisms contain the enzymes glutamate dehydrogenase and glutamine synthetase, which convert ammonia to glutamate and glutamine, respectively.
Number of enzymes required to synthesize the life-essential amino acids:

1. Glycine requires five enzymes 6, 7
2. Alanine can be obtained by three different synthesis pathways, and the number of enzymes is speculative. At least a transamination reaction is required, so i will put one enzyme. 8
3. Valine is derived from Pyruvate. Pyruvic acid can be made from glucose through glycolysis. 2 Nine enzymes are required to go from Glucose to pyruvate. A further pathway required three enzymes is required. 9 
4. Leucine The biosynthesis pathways of the branched-chain amino acids (valine, isoleucine and leucine) all begin with the same precursors (pyruvate or pyruvate and 2-ketobutyrate). Subsequently, four enzymes are required. 10 
5. Isoleucine The isoleucine pathway is almost the same as the valine biosynthesis pathway. 11
6. Methionine requires 4 enzymes, plus Vitamin B12  thirty enzymes are necessary for one of nature’s largest characterized biosynthetic pathways. 12
7. Proline: three enzymes are required in the pathway
8. Phenylalanine: one enzyme is needed. 13
9. Tryptophan biosynthesis is a biologically expensive, complicated process. In fact, the products of four other pathways are essential contributors of carbon or nitrogen during tryptophan formation. Thirteen enzymes are used 14
10. Serine requires three enzymes in its biosynthesis pathway 15
11. Threonine requires five enzymes in its biosynthesis pathway 16
12. Asparagine requires two enzymes in its biosynthesis pathway 17
13. Glutamine requires two enzymes in its biosynthesis pathway  18
14. Tyrosine requires two enzymes in its biosynthesis pathway 19
15. Cysteine requires one enzyme in its biosynthesis pathway 20
16. Lysine requires two enzymes in its biosynthesis pathway 21
17. Methionine requires two enzymes in its biosynthesis pathway 22
18. Threonine requires one enzyme in its biosynthesis pathway 23
19. Arginine requires eight enzymes in its biosynthesis pathway 24
20. Aspartate requires two enzymes in its biosynthesis pathway 25
21. Glutamate requires one enzyme in its biosynthesis pathway 26
22. Histidine requires eight enzymes in its biosynthesis pathway 27

A minimum of 112 enzymes are required to synthesize the 20 (+2) amino acids used in proteins

Carbohydrates
LUCA used the simplest and most ancient of the six known pathways of CO2 fixation, called the acetyl–CoA (or Wood–Ljungdahl) pathway. It uses nine enzymes. 

Membranes
At least 74 enzymes are required for phospholipid synthesis in prokaryotes 29

The origin of life: what we know, what we can know and what we will never know
A detailed understanding of that process will have to wait until ongoing studies in systems chemistry reveal both the classes of chemical materials and the kinds of chemical pathways that simple replicating systems are able to follow in their drive towards greater complexity and replicative stability.

Paul Davies, the fifth miracle page 53:
Pluck the DNA from a living cell and it would be stranded, unable to carry out its familiar role. Only within the context of a highly specific molecular milieu will a given molecule play its role in life. To function properly, DNA must be part of a large team, with each molecule executing its assigned task alongside the others in a cooperative manner. Acknowledging the interdependability of the component molecules within a living organism immediately presents us with a stark philosophical puzzle. If everything needs everything else, how did the community of molecules ever arise in the first place? Since most large molecules needed for life are produced only by living organisms, and are not found outside the cell, how did they come to exist originally, without the help of a meddling scientist? Could we seriously expect a Miller-Urey type of soup to make them all at once, given the hit-and-miss nature of its chemistry?

On the Development Towards the Modern World: A Plausible Role of Uncoded Peptides in the RNA World 5
2009
Arguably one of the most outstanding problems in understanding the progress of early life is the transition from the RNA world to the modern protein-based world. One of the main requirements of this transition is the emergence of mechanism to produce functionally meaningful peptides and later, proteins. What could have served as the driving force for the production of peptides and what would have been their properties and purpose in the RNA world?

My endnote: I have simplified the illustration, just to give an idea of the problem. In reality, a minimal, fully operational cell requires FAR many more enzymes than just what was mentioned above. But it shows the unbridgeable gap.

1. On the one side, we have the putative prebiotic soup with the random chaotic floating around of the basic building blocks of life, and on the other side,  the first living self-replicating cell ( LUCA ), a supposed fully operational minimal self-replicating cell, using the highly specific and sophisticated molecular milieu with a large team of enzymes which catalyze the reactions to produce the four basic building blocks of life in a cooperative manner, and furthermore, able to maintain intracellular homeostasis, reproduce, obtaining energy and converting it into a usable form, getting rid of toxic waste, protecting itself from dangers of the environment, doing the cellular repair, and communicate.  
2. The science paper: Structural analyses of a hypothetical minimal metabolism proposes a minimal number of 50 enzymatic steps catalyzed by the associated encoded proteins. They don't, however, include the steps to synthesize the 20 amino acids required in life. Including those, the minimal metabolome would consist of 221 enzymes & proteins. A large number of molecular machines, co-factors, scaffold proteins, and chaperones are not included, required to build this highly sophisticated chemical factory.
3. There simply no feasible viable prebiotic route to go from a random prebiotic soup to this minimal proteome to kick-start metabolism by unguided means. This is not a conclusion by ignorance & incredulity, but it is reasonable to be skeptic, that this irreducibly complex biological system, entire factory complexes composed of myriads of interconnected highly optimized production lines, full of computers and robots could emerge naturally defying known and reasonable principles of the limited range of random unguided events and physical necessity. Comparing the two competing hypotheses, chance vs intelligent design, the second is simply by far the more case-adequate & reasonable explanation.  


1. https://reasonandscience.catsboard.com/t2172-the-pentose-phosphate-pathway
2. https://reasonandscience.catsboard.com/t1796-glycolysis
3. https://reasonandscience.catsboard.com/t2590p25-origins-what-cause-explains-best-our-existence-and-why#5938
4. https://reasonandscience.catsboard.com/t2590p25-origins-what-cause-explains-best-our-existence-and-why#5942
5. https://reasonandscience.catsboard.com/t2708-nicotinamide-adenine-dinucleotide-nad-in-origin-of-life-scenarios
6. https://en.wikipedia.org/wiki/Template:Amino_acid_metabolism_enzymes
7. https://en.wikipedia.org/wiki/Glycine#Biosynthesis
8. https://en.wikipedia.org/wiki/Alanine#Biosynthesis
9. https://en.wikipedia.org/wiki/Valine#Synthesis
10. https://en.wikipedia.org/wiki/Leucine#Synthesis_in_non-human_organisms
11. https://en.wikipedia.org/wiki/Isoleucine#Biosynthesis
12. https://en.wikipedia.org/wiki/Methionine#Biosynthesis
13. https://en.wikipedia.org/wiki/Phenylalanine
14. https://en.wikipedia.org/wiki/Tryptophan#Biosynthesis_and_industrial_production
15. https://en.wikipedia.org/wiki/Serine#Synthesis_and_industrial_production
16. https://en.wikipedia.org/wiki/Threonine#Biosynthesis
17. https://en.wikipedia.org/wiki/Asparagine#Biosynthesis
18. https://en.wikipedia.org/wiki/Glutamine
19. https://en.wikipedia.org/wiki/Tyrosine#Biosynthesis
20. https://en.wikipedia.org/wiki/Cysteine
21. https://en.wikipedia.org/wiki/Lysine
22. https://en.wikipedia.org/wiki/Methionine#Biosynthesis
23. https://en.wikipedia.org/wiki/Threonine#Metabolism
24. https://reasonandscience.catsboard.com/t1740-amino-acids-origin-of-the-canonical-twenty-amino-acids-required-for-life#6063
25. https://en.wikipedia.org/wiki/Aspartic_acid#Biosynthesis
26. https://en.wikipedia.org/wiki/Glutamate_(neurotransmitter)#Biosynthesis
27. https://en.wikipedia.org/wiki/Histidine#Biosynthesis
28. https://reasonandscience.catsboard.com/t2967-fatty-acid-and-phospholipid-biosynthesis-in-prokaryotes
29. https://reasonandscience.catsboard.com/t2967-fatty-acid-and-phospholipid-biosynthesis-in-prokaryotes

https://manet.illinois.edu/pathways.php

From the prebiotic recruitment of the basic building blocks to create life to the transition of their synthesis in living cells, a major problem without invoking design

                                                                                                                                                                                                                                   
For life to begin, the various organic molecules had to be recruited abiotically. That is, there was no biological process at hand to manufacture by life's machinery it's very own building blocks. RNA, amino acids, lipids, and carbohydrates are all synthesized by complex metabolic networks inside the cell. But there was no such machinery lying around randomly to do the job on a prebiotic earth as pre-job. The struggle to explain the origin of life begins to understand where these building blocks came from. For this reason, panspermia is one of the proposals. That the building blocks were "imported" from meteorites for example.  

The Miller / Urey experiment, on the other hand, tried discharge experiments etc. to make just one of the building blocks, namely amino acids, with poor results ( nonetheless, even today heralded as proof that abiogenesis is possible ).  These building blocks had to be found in sufficient concentrations on earth, should not be annihilated by UV radiation, overcome the concomitant synthesis of undesired or irrelevant by-products, avoid the fact that water breaks down protein chains into amino acids, and somehow begin to chemically react and self-organize into interdependent complex form - and when the first living cell was created, find nutrition in form of glucose or starch - another huge problem, since these hydrocarbons are synthesized by photosynthesis - depending on cyanobacteria, or algae, which were not floating around yet. But let's suppose, the basic building blocks were there, all fully ready for action, and things would have had a go, naturally, by unguided random lucky events.  

The challenge would be enormous to organize these molecules themselves to create the extremely complex metabolic irreducible structures permitting the transition and begin all life essential processes to start creating these molecules independently from recruiting them from the surroundings. But then, for some miraculous reason, matter would simply start ignoring fully ready molecules lying around on the surroundings,  to create living cells, and rather select the basic elements, like sulfur, iron, phosphor, calcium, ammonia , etc. and  import them by extraordinarily complex import mechanisms, like membrane channel proteins, non-ribosomal peptide forming molecular machines, and transform the raw materials into useful form and molecules essential for life. Fe3 would be transformed into Fe2, and then joined with Sulfur, Molybdenum, and other trace metals, to start making active centers for various proteins. by such complex processes, which are still today not fully understood. Instantly, it would have to manage to create the active centers of essential proteins like helicase, otherwise, DNA replication would not occur, and the miracle of creating life would be a one generation job, a single event, happening once, and immediately disappear.

The huge problem is that   Reproduction. Metabolism.  Nutrition, Organization. Growth and development. creating various informational codes used in cellular processes, especially the genetic code, Information content.  Hardware/software entanglement. error check and repair, homeostasis, Permanence, and change, had to emerge all at once, in one single rapid shot.  Another key aspect is that there had to be a transition from recruiting first single complex monomers, amino acids only in levorotatory form ( left handed ) and dextrorotatory form ( RNA and DNA ), carbohydrates, and lipids, and all, at the same time, form bioactive chains. In case of amino acids, first dipeptides, and then polypeptides. In case of RNA and DNA, first constructing the single nucleic acids, that is joining the sugar and the base, then add phosphor, make all four information-bearing molecules, purines, and pyrimidines in sufficient quantity, fine-tune them to match in size and form, able to do informational Watson–Crick base-pairing, and join them into polynucleotides. Sugars would have to form into Disaccharides, and then into polysaccharides ( carbohydrates ).The first process would have no enzymes at hand, and the make of ATP had to emerge also at the same time, and the delivery of ATP energy for chemical processes also, instantly. So the question is how long chains could and would be formed without disintegrating soon after.....

Yup. Making life is a complex conundrum - and much ignorance and blind belief are going strong with the ones that think that time is enough to explain the origin of life. The more I learn, the more I understand that abiogenesis research is a waste of money. And atheist fool themselves, whey they say: " We don't know yet how life came to be, but one day, science will find out ". - But, of course, it was no deity - saying, Goddidit - is invoking magic - and a placeholder for ignorance. Nope. It's not. God is the logical rational answer to anyone, that actually knows what is involved.



Cartoon of the way complex polymers are built from many smaller units (monomers) using polymerization reactions. Many amino acids polymerize into proteins, simple sugars polymerize into complex carbohydrates, and nucleic
acid form from sugars plus bases plus phosphates.

In order to make the basic building blocks of life, following is the number of enzymes employed in the chemical cell factory:

https://reasonandscience.catsboard.com/t2894-prevital-unguided-origin-of-the-four-basic-building-blocks-of-life-impossible#8358

De novo Nucleotide synthesis
Folate is necessary for the production of DNA and RNA. The synthesis of NADPH requires 6 enzymes.  6 proteins are required in the folate pathway.   The pyrimidine synthesis pathway requires six regulated steps, 7 enzymes, and energy in the form of ATP. The starting material for purine biosynthesis is product of the highly complex pentose phosphate pathway, which uses 12 enzymes.  De novo purine synthesis pathway requires ten regulated steps, 11 enzymes, and energy in the form of ATP. In total 31 enzymes.  The replacement of RNA as the repository of genetic information is done by its more stable cousin, DNA, provides a more reliable way of transmitting information. DNA uses thymine (T) as one of its four informational bases, whereas RNA uses uracil (U).  At the C2' position of ribose, an oxygen atom is removed. The remarkable enzymes that do this are named Ribonucleotide reductases (RNR).  The  enzyme is essential for DNA synthesis, and most essential enzymes of life.  Uracil bases in RNA are transformed into thymine bases in DNA. The synthesis of thymine requires 7 enzymes. All in all, not considering the metabolic pathways and enzymes required to make the precursors to start RNA and DNA synthesis requires at least 26  enzymes.   In total, 57 enzymes.

De novo Amino Acid synthesis
Transamination reactions and other rearrangements promoted by enzymes containing pyridoxal phosphate (PLP), which requires 8 enzymes to be synthesized.  Transfer of one-carbon groups, with either tetrahydrofolate or S-adenosylmethionine as a cofactor; tetrahydrofolate is derived from the folate pathway,  Transfer of amino groups is derived from the amide nitrogen of glutamine. As implied by the root of the word (amine), the key atom in amino acid composition is nitrogen. All organisms contain the enzymes glutamate dehydrogenase and glutamine synthetase, which convert ammonia to glutamate and glutamine, respectively.
A minimum of 112 enzymes are required to synthesize the 20 (+2) amino acids used in proteins.

Carbohydrates
LUCA used the simplest and most ancient of the six known pathways of CO2 fixation, called the acetyl–CoA (or Wood–Ljungdahl) pathway. It uses nine enzymes. 

Phospholipid Membranes
At least 74 enzymes are required for phospholipid synthesis in prokaryotes 29

1. On the one side, we have the putative prebiotic soup with the random chaotic floating around of the basic building blocks of life, and on the other side,  the first living self-replicating cell ( LUCA ), a supposed fully operational minimal self-replicating cell, using the highly specific and sophisticated molecular milieu with a large team of enzymes which catalyze the reactions to produce the four basic building blocks of life in a cooperative manner, and furthermore, able to maintain intracellular homeostasis, reproduce, obtaining energy and converting it into a usable form, getting rid of toxic waste, protecting itself from dangers of the environment, doing the cellular repair, and communicate.  
2. The science paper: Structural analyses of a hypothetical minimal metabolism proposes a minimal number of 50 enzymatic steps catalyzed by the associated encoded proteins. They don't, however, include the steps to synthesize the 20 amino acids required in life. Including those, the minimal metabolome would consist of 221 enzymes & proteins. A large number of molecular machines, co-factors, scaffold proteins, and chaperones are not included, required to build this highly sophisticated chemical factory.
3. There simply no feasible viable prebiotic route to go from a random prebiotic soup to this minimal proteome to kick-start metabolism by unguided means. This is not a conclusion by ignorance & incredulity, but it is reasonable to be skeptic, that this irreducibly complex biological system, entire factory complexes composed of myriads of interconnected highly optimized production lines, full of computers and robots could emerge naturally defying known and reasonable principles of the limited range of random unguided events and physical necessity. Comparing the two competing hypotheses, chance vs intelligent design, the second is simply by far the more case-adequate & reasonable explanation.