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Where did Glucose come from in a prebiotic world ?

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Where did Glucose come from in a prebiotic world ?

http://reasonandscience.catsboard.com/t2419-where-did-glucose-come-from-in-a-prebiotic-world

Before respiration (>2,600 Ma ago), the major energy production pathway was anaerobic glycolysis, where C6 sugars (glucose, fructose) were broken down to C3 carbohydrates (pyruvate). It is thought that the sugars were
taken from the environment, formed by high temperatures and electrical discharges through the ancient atmosphere according to the Stanley Miller experiments mimicking the ancient atmospheric composition and physical factors (flashes, temperature8). (ii) 16

A 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 15 To date, there are six known carbon fixation pathways used by living organisms. One of them, the r-TCA cycle is often proposed as the leading candidate to be the first carbon fixation mechanism because it operates in ancient green sulfur bacteria (e.g., Chlorobium). A prebiotic system should have also been able to implement the core reactions involved in central metabolism abiotically and nonenzymatically. 15

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. Glucose, a six-carbon sugar, is the primary energy source for most cells and the principal sugar used to glycosylate the proteins and lipids that form the outer coat of all cells. Plants have exploited the structural potential of sugars in their production of cellulose; wood, bark, grasses, and reeds are all polymers of glucose and other monosaccharides.

Glucose is a ubiquitous fuel in biology. It is used as an energy source in most organisms, from bacteria to humans, through either aerobic respiration, anaerobic respiration, or fermentation. Sugar phosphates are however constituents of many molecules, such as RNA, DNA, ATP and lipids, which are inevitably connected with the emergence of life. It is the fundamental role of sugar phosphates, and the virtual universality of their few metabolic interconversion sequences, that places their origin to the very early stages in the history of life. Glucose is used by Glycolysis,  which is  the most universal pathway in all energy metabolism, occurring in almost every living cell.  The glycolytic pathway is multifunctional. Thus it provides the cell with energy  (ATP)] from glucose catabolism - the process that breaks down molecules into smaller units.  Glucose is the human body's key source of energy. Through glycolysis and later in the reactions of the citric acid cycle and oxidative phosphorylation, glucose is oxidized to eventually form CO2 and water, yielding energy mostly in the form of ATP. 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.

Quite apart from the fact that it is dependent on the reducing nature of the environment (the thermodynamic factor), the synthesis of organic molecules from sources of carbon such as CO2 or CH4; of hydrogen such as H2 or CH4; or of nitrogen such as N2 or NH3 is not spontaneous. These precursors are themselves poorly reactive. Synthesis can, therefore, proceed only through some activation, either thermal in nature (through lightning during thunderstorms, through the impact of meteorites with the Earth, at hydrothermal vents, etc.) or photochemical in nature (provided that the photons should carry sufficient energy to make up for the bonds to be broken). Under such conditions, transient, highly reactive species would be supposedly formed, and random recombinations yield small organic molecules within the activated mixture. However, these organic molecules are also sensitive to activation processes: if UV radiation is able to activating mixtures of simple gases, it also has a destructive effect on organic molecules. Similarly, in hydrothermal systems, these same molecules are easily destroyed by high temperature water (often 350 °C, or even more). To be preserved, these freshly synthesized molecules must therefore be isolated from the activation system; for instance, by condensation and rain in the atmosphere, or else by circulation in hydrothermal systems.

Both the amounts and forms of energy brought into play and the time-scales of activation processes (fractions of a nanosecond for photochemistry, fractions of a second for electrical discharges, and much greater durations for hydrothermal circulations) will affect the nature of the molecules that are formed. In particular, the latter themselves will remain in an activated state if the duration of the activation is short when compared with the rate of the subsequent deactivation reactions, or of the return to an equilibrium state, as well as of the transfer rate. Molecules formed in hydrothermal systems are close to thermodynamic equilibrium and are no longer reactive, unless there is an external source of energy. In addition, any analysis of the productive or destructive nature of any activation process must take into account the efficiency of these transfers towards a protected environment, where a chemistry that could truly be described as prebiotic could develop. Such an environment would be likely to offer conditions suitable for the synthesis of the building blocks of life (biomolecules) and even for more complex assemblies. It may be noted that, in addition to this transfer, an effective prebiotic chemistry would call for a process of concentration (dilution in the ocean is of such a nature that it would make any subsequent constructive chemistry impossible, simply because any significant encounter between organic molecules would become highly unlikely, and that these latter would be fated only to degrade). It would at least require a sequestration of the molecules that had been formed within a limited space, as is the case with adsorption on the surface of a mineral (thus enabling interactions between them, and as a result, the formation of molecules of a more significant size). 17


Some of the conditions governing the prebiotic synthesis of organic matter. 
The precursors of organic matter present in a reducing environment are poorly reactive, whence the necessity for their activation. This process of activation may destroy the synthesized molecules, whence the requirement to transfer the reaction products into a protected environment, where a truly prebiotic chemistry may possibly take place. 17

Chemical Energy of Organic Substrates: Carbohydrates  12
The environment of the prebiotic Earth was far from equilibrium, so that a variety of chemical reactions were occurring simultaneously. The problem is to gain some understanding of which of these was relevant to the origin of life, and how they were incorporated. Living systems today use chemical reactions to release energy in small steps called metabolism, which can be defined as a series of chemical reactions linked in a molecular system that provides energy and small molecules required for growth. Each step is catalyzed by a specific enzyme, and the reaction rates are controlled by feedback loops in which a product is an allosteric inhibitor of the enzyme to be regulated. If the first life was heterotrophic, what nutrients might have been available as a source of chemical energy?

Of all the organic substrates, sugars are by far the most attractive organic energy substrate of primitive anaerobic life, because they are able to provide all the energy and carbon needed for the growth and maintenance of a fermentative metabolism. In fact, the sugars that are the first substrates of the glycolytic pathway can be considered to be optimal biosynthetic substrates because they contain mainly alcohol groups that have maximum self-transformation energy, and a single carbonyl group (aldehyde or ketone) that makes them reactive and able to form covalent adducts to enzyme active sites (Weber 2004). Moreover, in fermentation, the energy content of sugars is converted to the anhydride energy of ATP by substrate-level oxidation phosphorylation, a process that does not require the organized membrane structures of phosphorylation coupled to electron transfer. As discussed later, the energy content and reactivity of sugars also allows them to act as substrates for chemically spontaneous synthetic processes that yield many of the molecular products required for the origin of life. Such sugar-driven syntheses require no external source of chemical energy (Weber 2000).

In addition to being the sole energy and carbon source of fermentative organisms today, sugars have chemical properties that make them very attractive substrates for synthetic processes needed for the origin of life. First, sugars can be synthesized under plausible prebiotic conditions from formaldehyde and glycolaldehyde by the formose reaction (Schwartz and de Graaf 1993; See also Benner et al. 2010). Second, sugars are reactive and contain considerable self-transformation energy, properties that allow them to react with ammonia, yielding many types of molecules needed for the origin of life. These sugar-driven syntheses require no additional source of chemical energy (Weber 2000).

The synthetic versatility of sugars is shown by their spontaneous reactions in the presence of ammonia that yield catalytic amines, biomonomers (amino acids), metabolites (pyruvate, glycolate), energy molecules (hydroxy and amino acid thioesters), alternative nucleobases (2-pyrazinones that resemble uracil), heterocyclic molecules (furans, pyrroles, imidazoles, pyridines, and pyrazines), polymers (polypyrroles and polyfurans), and cell-like organic microspherules (Weber 2001-2008, refs. therein). Sugars have also been shown to drive the prebiotic synthesis of ammonia from nitrite. Remarkably, these prebiotic synthetic processes based on sugar chemistry can evolve directly into modern sugar-driven biosynthesis without violating the principle of evolutionary continuity.

Finally, sugar synthesis from formaldehyde and glycolaldehyde, and the subsequent conversion of sugar products to carbonyl-containing products can be catalyzed by small molecules (ammonia and amines including amino acids and peptides). In fact, small l-dipeptides (the isomer found in proteins) stereoselectively catalyzed the formation of d-ribose (Pizzarello and Weber 2010). These ammonia and amine-catalyzed reactions yielded aldotriose (glyceraldehyde), ketotriose (dihydroxyacetone), aldotetroses (erythrose and threose), ketotetrose (erythrulose), pyruvaldehyde, acetaldehyde, glyoxal, pyruvate, glyoxylate, and several unidentified carbonyl products. The uncatalyzed control reaction yielded no pyruvate or glyoxylate, and only trace amounts of pyruvaldehyde, acetaldehyde, and glyoxal. With l-alanine, the rates of triose and pyruvaldehyde synthesis were about 15-times and 1200-times faster, respectively, than the uncatalyzed reaction (Weber 2001). Because amines are also products of sugar–ammonia reactions, these studies suggested that the sugar–ammonia reaction could be autocatalytic. This possibility was tested in a later study, which showed that reaction of the triose sugar (glyceraldehyde) with ammonia yielded a crude product mixture capable of catalyzing a 10-fold acceleration of the same sugar–ammonia reaction that produced the catalytic products (Weber 2007).

 

Gluconeogenesis is a reverse process to glycolysis, which produces Glucose. 
Nonenzymatic reactions that would be precursor mechanisms to glyconeogenesis,  leading to the biosynthesis of glucose
Metabolic networks are largely composed of intermediate substrates that are not characterized by long‐time stability, at least when considering geological environments and timescales.  In addition, large sugar phosphates are not frequently generated in experiments that address scenarios of primordial carbon fixation.
A paper reports that Fe(II) was broadly available before oxygenation of the early Earth, implying a scenario for the first glycolytic enzymes being simple iron-binding RNA or oligopeptide molecules, which would have possessed the potential of enhancing many reactions now found in central metabolism.

Did you read that carefully ?  This is a ridiculous pseudoscientific  festival of just so made up fairy tale stories based on wishful thinking.  We shall believe that unspecified metal catalysts where somehow ( HOW ??!! ) transformed miraculously and bridged a hudge gap from unspecified chemical reactions  into the highly complex specific enzymes, highly regulated by other complex mechanisms,  required in these pathways. If such baseless assertions would have been made in ANY other discipline of science, the authors would have been ridiculed. Not so in biochemistry, where any fantastic story is PLAUSIBLE, and is swallowed as serious science. 

A paper from Nature magazines reported that Carbonaceous meteorites were a source of sugar-related organic compounds for the early Earth. They claimed :
Sugars, sugar alcohols and sugar acids are vital to all known lifeforms - they are components of nucleic acids (RNA, DNA), cell membranes and also act as energy sources. But there has hitherto been no conclusive evidence for the existence of polyols in meteorites, leaving a gap in our understanding of the origins of biologically important organic compounds on Earth.
Analyses of water extracts indicate that extraterrestrial processes including photolysis and formaldehyde chemistry could account for the observed compounds. We conclude from this that polyols were present on the early Earth and therefore at least available for incorporation into the ®️rst forms of life.
Just because something COULD HAVE happened on the early earth, they conclude IT DID happen. The logical fallacy is evident.

1. Natural pro­cesses tend to produce gunk with little relevance to life.
2. The amounts of these chemicals were tiny—far too low to contribute to biological processes.
3. Chemical reactions would have somehow to select the useful compounds amongst   contaminated gunk.
4. Sugars are very unstable, and easily decompose or react with other chemicals.
5. Living things require homochiral sugars, i.e. with the same ‘handedness’, but these ones would not have been.
6. There is no plausible method of making the sugar ribose join to some of the essential building blocks needed to make DNA or RNA, let alone into RNA or DNA themselves
7. Even DNA or RNA by themselves would not be life, since it’s not enough to just join the bases (‘letters’) together, but the se­quence of the letters must consitute meaningful information.
8. Even this letter sequence would be meaningless without elaborate decoding machinery to translate this into amino acid sequences.
 
Chemisynthesis is employed by organisms that live in the environment around deep-sea volcanic vents, where hot, hydrogen sulfide-rich waters pour out of newly formed ocean crust.  Such waters, compared to the colder, sulfide-poor adjacent regions, have an abundant supply of free energy. This term refers to a source of energy that can be utilized readily to do some form of work, such as sustain biological processes, or can be stored in high-energy phosphate bonds. One readily available means to extract energy from the vents is to combine hydrogen sulfide with oxygen to form sulfur dioxide with production of energy. Such a process is possible in an ocean that has free oxygen available, but would not work on the primitive, pre-oxygen-rich Earth. Other biochemical cycles that use sulfur but not oxygen are conducted by some prokaryotic organisms, but these capture much less energy than the oxygendriven cycles. As with fermentation, chemisynthesis without free oxygen was the hallmark of a rather sluggish primitive biota.

Further problems:

There would have had to exist a cell membrane, dividing the outside from the inside of the proto-cell, to protect the chemical reactions, and complex gates regulating the compound entrance into the cell. That is another serious problem for origin of life research:

even in the simplest cells, the membrane is a biological device of a staggering complexity that carries diverse protein complexes mediating energy-dependent – and tightly regulated - import and export of metabolites and polymers  Remarkably, even the author of the book: Agents Under Fire: Materialism and the Rationality of Science, pgs. 104-105 (Rowman & Littlefield, 2004). HT: ENV. asks the readers:
Hence a chicken and egg paradox: a lipid membrane would be useless without membrane proteins but how could membrane proteins have evolved in the absence of functional membranes?

The book Origins of Life on the Earth and in the Cosmos tries to solve the ridde as follows :
Membrane-enclosed cells came into being some time after the first ribozymes and definitely before the advent of translation systems.  It is highly likely that these primitive living systems were sequestered in some way, possibly by adhering to clay surfaces. It is also likely that the first fatty acids used to make cellular membranes were made under conditions that would have been too harsh to share with living systems that are far more delicate. In view of this we must ask how the first membranes made contact with the early membrane- free living systems. How could life exist without membranes ?
Then we must consider how the early living systems became enclosed by these membranes and how the membranes of these most primitive cells evolved. True. Big questions, isnt it?
The encapsulation of the living systems into the liposomes was probably a simple process that required no more than one or two dry–wet cycles.

The pseudo-scientific just so stories are remarkable, aren't they ?! The conclusion  is that naturalistic explanations do not suffice to answer the relevant question in a satisfying manner, where Glucose came from, adding to all other unbridgeable problems of origin of life research, and thus giving proponents of intelligent design good reasons to infer intelligent design as the better explanation.



Glucose is a ubiquitous fuel in biology. It is used as an energy source in most organisms, from bacteria to humans, through either aerobic respiration, anaerobic respiration, or fermentation. Glucose is the human body's key source of energy. Through glycolysis and later in the reactions of the citric acid cycle and oxidative phosphorylation, glucose is oxidized to eventually form CO2 and water, yielding energy mostly in the form of ATP. 6
Cells require ATP to manufacture enzymes before glycolysis can even occur. (The old adage of “it takes money to make money” is applicable here—it takes energy to produce energy!) As such, proponents of natural mechanisms have an enormous chicken-egg problem. Which came first, glycolysis to make energy or energy from glycolysis needed to make enzymes? Without the enzymes, glycolysis could not occur to produce ATP. But without the ATP those enzymes could not be manufactured. This is strong evidence that the process of cellular respiration is not the product of evolution.

The 6C sugar glucose is a basic energy source for plants and animals, and they are joined in chains to form the cellulose of plant cell walls, as well as the energy storage molecules starch (plants) and glycogen (animals). 7 The ultimate origin of sugars is a huge problem for those who believe in abiogenesis, the idea that non-living chemicals evolved into living cells without any intelligent input

The source of glucose and other sugars used in metabolic processes must lie in an energy-collecting process. Without some means to create such sugar, limitations of food supply for metabolic processes would be far more severe than they actually are.

In plants and some prokaryotes, glucose is a product of photosynthesis. In plants, and in animals and fungi, glucose also is produced by the breakdown of polymeric forms of glucose—glycogen (animals, fungi) or starch (plants); the cleavage of glycogen is termed glycogenolysis of starch, starch degradation.[23] In animals, glucose is synthesized in the liver and kidneys from non-carbohydrate intermediates, such as pyruvate, lactate and glycerol, in the process of gluconeogenesis. In some deep-sea bacteria, glucose is produced by chemosynthesis. 4

Possible explanations :

1.Where did the glucose come from?
If you know that biosynthesis of glucose is required before you can degrade it then why not look at nonenzymatic reactions that could lead to the biosynthesis of glucose instead of reactions that break it down?
http://sandwalk.blogspot.com.br/2016/01/where-did-glucose-come-from.html

Non‐enzymatic glycolysis and pentose phosphate pathway‐like reactions in a plausible Archean ocean 8
The metabolic network possesses a remarkably similar basic structure in all organisms examined. This indicates that it came into being at a very early stage of evolution and that its reaction sequences follow highly optimized routes (Jeong et al, 2000; Noor et al, 2010). The evolutionary origins of this network structure are, however, still largely unknown (Luisi, 2012). It is assumed that the pathways that mediate sugar phosphate interconversion, glycolysis, the pentose phosphate pathway, as well as the related Entner‐Doudoroff pathway and Calvin cycle are evolutionarily ancient, as they are conserved and fulfil their central metabolic functionality virtually ubiquitously. Known as central, or primary, metabolism, their reaction sequences provide ribose 5‐phosphate for the backbone of RNA and DNA, building blocks for the synthesis of co‐enzymes, amino acids and lipids and supply the cell with energy in form of ATP and redox equivalents.

One of the difficulties in describing the origin of metabolism is the fact that the metabolic network is largely composed of intermediates that are not characterized by long‐time stability, at least when considering geological environments and timescales. As shown here and previously, this in particular applies to sugar phosphate molecules [(Larralde et al, 1995). In addition, large sugar phosphates are not frequently generated in experiments that address scenarios of primordial carbon fixation (Cody, 2000; Fuchs, 2011; Hügler & Sievert, 2011). This difficulty cannot, however, mask the fact that sugar phosphates are constituents of many molecules, such as RNA, DNA, ATP and lipids, which are inevitably connected with the emergence of life. It is the fundamental role of sugar phosphates, and the virtual universality of their few metabolic interconversion sequences, that places their origin to the very early evolutionary stages.

The widespread role of non-enzymatic reactions in cellular metabolism 9
Enzymes shape cellular metabolism, are regulated, fast, and for most cases specific. How did they get there to be all that ?
Enzymes do not however prevent the parallel occurrence of non-enzymatic reactions. The frequent occurrence of non-enzymatic reactions impacts on stability and metabolic network structure.
That means increased difficulty to setup enzymatic pathways paralles and nearby nonenzymatic reactions.
Glycolysis and gluconeogenesis, pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle are central metabolic pathways and exemplary for the conservation of metabolism Their products glucose, pyruvate, ribose-5-phosphate and erythrose-4-phosphate are common precursors for amino acids, lipids and nucleotides.  
Sequences of glycolytic enzymes differ between Archaea and Bacteria/Eukaryotes How that combines with a Last common universal ancestor is a mistery to me....
A plausible primordial base can be traced for glycolysis and the PPP, as several of their reactions can be replicated with metal catalysts, in particular Fe(II), under conditions reproducing the ocean chemistry of the Archean world . Fe(II) was broadly available before oxygenation of the early Earth,

implying a scenario for the first glycolytic enzymes being simple iron-binding RNA or oligopeptide molecules, which would have possessed the potential of enhancing many reactions now found in central metabolism.

Did you read that carefully ?  This is a ridiculous pseudoscientific  festival of just so made up fairy tale stories based on wishful thinking, nothing else !! We shall believe that unspecified metal catalysts where somehow ( HOW ??!! ) transformed miraculously into the highly complex specific enzymes required in these pathways. If such baseless assertions would have been made in ANY other discipline of science, the authors would have been ridiculed. Not so in biochemistry, where any fantastic story is PLAUSIBLE, and is swallowed as serious science. GIVE ME A BREAK !!   

Catalysts are required not only to accelerate chemical reactions, but also to achieve specificity in reaction systems—uncatalysed chemical reactions can lead to a large set of unspecific products, while catalysts limit the reaction space by preferring a specific reaction.

2. Carbonaceous meteorites as a source of sugar-related organic compounds for the early Earth 10
Sugars, sugar alcohols and sugar acids are vital to all known lifeforms - they are components of nucleic acids (RNA, DNA), cell membranes and also act as energy sources. But there has hitherto been no conclusive evidence for the existence of polyols in meteorites, leaving a gap in our understanding of the origins of biologically important organic compounds on Earth.
Analyses of water extracts indicate that extraterrestrial processes including photolysis and formaldehyde chemistry could account for the observed compounds. We conclude from this that polyols were present on the early Earth and therefore at least available for incorporation into the ®️rst forms of life.
Just because something COULD HAVE happened on the early earth, they conclude IT DID happen. The logical fallacy is evident.




Source : 7


3. Chemisynthesis 5

is employed by organisms that live in the environment around deep-sea volcanic vents, where hot, hydrogen sulfide-rich waters pour out of newly formed ocean crust (Figure 12.6).  



Such waters, compared to the colder, sulfide-poor adjacent regions, have an abundant supply of free energy. This term refers to a source of energy that can be utilized readily to do some form of work, such as sustain biological processes, or can be stored in high-energy phosphate bonds. One readily available means to extract energy from the vents is to combine hydrogen sulfide with oxygen to form sulfur dioxide with production of energy. Such a process is possible in an ocean that has free oxygen available, but would not work on the primitive, pre-oxygen-rich Earth. Other biochemical cycles that use sulfur but not oxygen are conducted by some prokaryotic organisms, but these capture much less energy than the oxygendriven cycles. As with fermentation, chemisynthesis without free oxygen was the hallmark of a rather sluggish primitive biota.



Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because glucose is a vital source of energy for all life, these transporters are present in all phyla.
https://en.wikipedia.org/wiki/Glucose_transporter

The Interdependency of Lipid Membranes and Membrane Proteins  11

even in the simplest cells, the membrane is a biological device of a staggering complexity that carries diverse protein complexes mediating energy-dependent – and tightly regulated - import and export of metabolites and polymers
Remarkably, even the author of the book: Agents Under Fire: Materialism and the Rationality of Science, pgs. 104-105 (Rowman & Littlefield, 2004). HT: ENV. asks the readers:
Hence a chicken and egg paradox: a lipid membrane would be useless without membrane proteins but how could membrane proteins have evolved in the absence of functional membranes?

Membrane-enclosed cells came into being some time after the first ribozymes and definitely before the advent of translation systems. 3 It is highly likely that these primitive living systems were sequestered in some way, possibly by adhering to clay surfaces It is also likely that the first fatty acids used to make cellular membranes were made under conditions that would have been too harsh to share with living systems that are far more delicate. In view of this we must ask how the first membranes made contact with the early membrane- free living systems. How could life exist without membranes ?
Then we must consider how the early living systems became enclosed by these membranes and how the membranes of these most primitive cells evolved. True. Big questions, isnt it?

The encapsulation of the living systems into the liposomes was probably a simple process that required no more than one or two dry–wet cycles. The pseudo-scientific just so stories are remarkable, aren't they ?!

Does Gluconeogenesis answer where glucose came from in a prebiotic world ?

Usually produced only in hepatocytes, in fasting conditions other tissues such as the intestines, muscles, brain, and kidneys are able to produce glucose following activation of gluconeogenesis.

MOST OF THE ENZYMES USED IN GLYCOLYSIS ARE USED IN THE REVERSE PROCESS OF SUGAR SYNTHESIS
Glycolysis and gluconeogenesis constitute a set of oppositely directed conversions. The organization of glycolysis as a series of connected metabolic pools makes it possible for most of the same enzymes to function in both directions (Fig. 2). Only at three points, all outside the metabolic pools, do we find reactions in gluconeogenesis that use different enzymes: 

(1) the conversion of pyruvate to phosphoenolpyruvate (PEP), 
(2) the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate, and 
(3) the conversion of hexose phosphate to storage polysaccharide or hexose phosphate to glucose. 

At these three points we find sizable energy drops in the glycolytic direction (see Table 1). 



Clearly, if cells are to conduct these reactions in the reverse direction, the three reactions must have a different ATP-to- ADP  Stoichiometry and accordingly different enzymes are required (see Fig. 2).




Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. From breakdown of proteins,these substrates include glucogenic amino acids (although not ketogenic amino acids); from breakdown of lipids (such as triglycerides), they include glycerol (although not fatty acids); and from other steps in metabolism they include pyruvate and lactate. Gluconeogenesis is one of several main mechanisms used by humans and many other animals to maintain blood glucose levels, 2

https://upload.wikimedia.org/wikipedia/commons/0/08/Gluconeogenesis_pathway.png



Gluconeogenesis is a pathway consisting of a series of eleven enzyme-catalyzed reactions. The pathway may begin in the mitochondria or cytoplasm (of the liver/kidney), this being dependent on the substrate being used. Many of the reactions are the reverse of steps found in glycolysis.

Pathway
Gluconeogenesis is a pathway consisting of a series of eleven enzyme-catalyzed reactions. The pathway may begin in the mitochondria or cytoplasm (of the liver/kidney), this being dependent on the substrate being used. Many of the reactions are the reverse of steps found in glycolysis.[/size]
Gluconeogenesis begins in the mitochondria with the formation of oxaloacetate by the carboxylation of pyruvate. This reaction also requires one molecule of ATP, and is catalyzed by pyruvate carboxylase. This enzyme is stimulated by high levels of acetyl-CoA (produced in β-oxidation in the liver) and inhibited by high levels of ADP and glucose.
Oxaloacetate is reduced to malate using [url=https://www.revolvy.com/topic/Nicotinamide adenine]NADH[/url], a step required for its transportation out of the mitochondria.
Malate is oxidized to oxaloacetate using NAD+ in the cytosol, where the remaining steps of gluconeogenesis take place.
Oxaloacetate is decarboxylated and then phosphorylated to form phosphoenolpyruvate using the enzyme PEPCK. A molecule of GTP is hydrolyzed to GDP during this reaction.
The next steps in the reaction are the same as reversed glycolysis. However, fructose 1,6-bisphosphatase converts fructose 1,6-bisphosphate to fructose 6-phosphate, using one water molecule and releasing one phosphate (in glycolysis, phosphofructokinase 1 converts F6P and ATP to F1,6BP and ADP). This is also the rate-limiting step of gluconeogenesis.
Glucose-6-phosphate is formed from fructose 6-phosphate by phosphoglucoisomerase (the reverse of step 2 in glycolysis). Glucose-6-phosphate can be used in other metabolic pathways or dephosphorylated to free glucose. Whereas free glucose can easily diffuse in and out of the cell, the phosphorylated form (glucose-6-phosphate) is locked in the cell, a mechanism by which intracellular glucose levels are controlled by cells.
The final reaction of gluconeogenesis, the formation of glucose, occurs in the lumen of the endoplasmic reticulum, where glucose-6-phosphate is hydrolyzed by glucose-6-phosphatase to produce glucose and release an inorganic phosphate. Like two steps prior, this step is not a simple reversal of glycolysis, in which hexokinase catalyzes the conversion of glucose and ATP into G6P and ADP. Glucose is shuttled into the cytoplasm by glucose transporters located in the endoplasmic reticulum's membrane.

Regulation
While most steps in gluconeogenesis are the reverse of those found in glycolysis, three regulated and strongly endergonic reactions are replaced with more kinetically favorable reactions. Hexokinase/glucokinase, phosphofructokinase, and pyruvate kinase enzymes of glycolysis are replaced with glucose-6-phosphatase, fructose-1,6-bisphosphatase, and PEP carboxykinase/pyruvate carboxylase. These enzymes are typically regulated by similar molecules, but with opposite results. For example, acetyl CoA and citrate activate gluconeogenesis enzymes (pyruvate carboxylase and fructose-1,6-bisphosphatase, respectively), while at the same time inhibiting the glycolytic enzyme pyruvate kinase. This system of reciprocal control allow glycolysis and gluconeogenesis to inhibit each other and prevents a futile cycle of synthesizing glucose to only break it down.[/size]
The majority of the enzymes responsible for gluconeogenesis are found in the cytosol; the exceptions are mitochondrial pyruvate carboxylase and, in animals, phosphoenolpyruvate carboxykinase. The latter exists as an isozyme located in both the mitochondrion and the cytosol.[24] The rate of gluconeogenesis is ultimately controlled by the action of a key enzyme, fructose-1,6-bisphosphatase, which is also regulated through signal transduction by [url=https://www.revolvy.com/topic/Cyclic adenosine]cAMP[/url] and its phosphorylation.[/size]
Global control of gluconeogenesis is mediated by glucagon (released when blood glucose is low); it triggers phosphorylation of enzymes and regulatory proteins by [url=https://www.revolvy.com/topic/Protein kinase]Protein Kinase A[/url] (a cyclic AMP regulated kinase) resulting in inhibition of glycolysis and stimulation of gluconeogenesis. Recent studies have shown that the absence of hepatic glucose production has no major effect on the control of fasting plasma glucose concentration. Compensatory induction of gluconeogenesis occurs in the kidneys and intestine, driven by glucagon, glucocorticoids, and acidosis.[25]

Question: Had mitochondria, the cytoplasm, and the cell membrane not have to be present for gluconeogenesis to be possible?

Gluconeogenesis begins in the mitochondria with the formation of oxaloacetate by the carboxylation of pyruvate. This reaction also requires one molecule of ATP, and is catalyzed by pyruvate carboxylase. This enzyme is stimulated by high levels of acetyl-CoA (produced in β-oxidation in the liver) and inhibited by high levels of ADP and glucose.

Question : Had pyruvate carboxylase and acetyl-CoA not have to be present for gluconeogenesis to start ?

The chemical logic behind... Gluconeogenesis 1

The human body has two main ways to keep constant blood glucose levels between meals: glycogen degradation and gluconeogenesis. Gluconeogenesis is the synthesis of glucose from other organic compounds (pyruvate, succinate, lactate, oxaloacetate, etc. Most of the reactions involved are quite similar to the reverse of glycolysis. Indeed, almost all reactions in glycolyis are readily reversible under physiological conditions. The three exceptions are the reactions catalyzed by :



In gluconeogenesis, every one of these steps is replaced by thermodinamically favorable reactions. Among these three reactions, phosphoenolpyruvate synthesis from pyruvate is the most energy-demanding, since its DG is rather positive. In order to overcome this thermodynamic barrier, the reaction will be coupled to a decarboxylation, a strategy often used by the cell to displace an equilibrium towards the formation of products, as it will also be observed in several reactions in the citric acid cycle. Since both pyruvate and phosphoenolpyruvate(PEP) are three-carbon compounds, pyruvate must be carboxylated to a four-carbon compound, oxaloacetate (OAA), before such a decarboxylation can happen. The enzyme responsible for pyruvate carboxylation (pyruvate carboxylase) is present inside the mithocondrial matrix, and contains biotin, a CO2-activating cofactor. The energy required for the carboxylation comes from from the hydrolysis of ATP. Oxaloacetate decarboxylation releases the energy needed to enable C2 phosphorylation by GTP, yielding phosphoenolpyruvate (in a reaction catalyzed bynuma phosphoenolpyruvate carboxykinase - PEPCK).



To create energy, these early bacteria probably consumed naturally occurring amino acids. Amino acids, sugars, and other organic compounds formed spontaneously in the atmosphere then dissolved in liquid water. 13

Peanuts, isn't it ?

1. http://homepage.ufp.pt/pedros/bq/gng.htm
2. https://www.revolvy.com/main/index.php?s=Gluconeogenesis
3. Origins of Life on the Earth and in the Cosmos
4. https://en.wikipedia.org/wiki/Glucose#Biosynthesis
5. Earth Evolution of a Habitable World page 138
6. http://reasonandscience.heavenforum.org/t2158-glucose-and-its-importance-for-life?highlight=glucose
7. http://creation.com/sugars-from-space-do-they-prove-evolution
8. http://msb.embopress.org/content/10/4/725?ijkey=d312c6a6f5d85d933490d25a21a64c153a6cacf8&keytype2=tf_ipsecsha#sec-2
9. http://www.sciencedirect.com/science/article/pii/S0958166914002353
10. http://www.nature.com/nature/journal/v414/n6866/full/414879a.html
11. http://reasonandscience.heavenforum.org/t2397-the-interdependency-of-lipid-membranes-and-membrane-proteins
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828274/
13. http://www.windows2universe.org/earth/Life/first_life.html
14. The cell, Panno, page 8
15. Origins of Life: The Primal Self-Organization,   page 96
16. Prebiotic Evolution and Astrobiology, page 13
17. Young Sun, Early Earth and the Origins of Life , page 83



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Laurence Moran wrote:
The breakdown of glucose (glycolysis) uses some of the same enzymes used in gluconeogenesis except they catalyze the reverse reaction. (All enzymes catalyze reactions in both directions.) Thus, some of the enzymes required for glyolysis were already present making it easier for the glycolytic pathway to evolve millions of years after the gluconeogenesis pathway arose.

You cannot get around the fact which i mentioned already: Whatever first pathway you replace glycolysis with, it has to be a complex multi-step process , requiring a number of enzymes and regulation. And you will ALWAYS be confronted with the initial problem exposed : it takes energy to make energy. If Gluconeogenesis came before or not, does not change anything in that fundamental problem. 

Following paper makes the same assertion:
Evolution of the coordinate regulation of glycolytic enzyme genes by hypoxia
The first glycolytic enzymes in the Archean period probably contributed mainly anabolic, gluconeogenic functions (Conway, 1992; Romano and Conway, 1996; Selig et al., 1997), with catabolic functions being acquired subsequently as kinases appeared to use ATP, ADP or pyrophosphate as phosphate shuttles (Romano and Conway, 1996).
http://jeb.biologists.org/content/206/17/2911

They just assert  catabolic functions were being acquired subsequently . How ?! 3 enzymes had to be replaced to generate a reverse function.  

Many papers mention glycolysis as one of the most conserved and fundamental metabolic pathways.

Monroe Strickberger, Evolution, page 13:  
"Anaerobic glycolysis, the breakdown of glucose in the absence of oxygen, is perhaps the most elemental metabolic pathway, and all living creatures share various sections of this pathway.This universality seems to depend on the fact that all existing organisms derive their free energy from the chemical breakdown of such monosaccharides."

Origins of Life on the Earth and in the Cosmos pg. 194
"Glycolysis is the most ubiquitous pathway in all energy metabolism, occurring in almost every living cell."

The Origin and Evolution of Cells
"In the initially anaerobic atmosphere of Earth, the first energy-generating reactions presumably involved the breakdown of organic molecules in the absence of oxygen. These reactions are likely to have been a form of present-day glycolysis—the anaerobic breakdown of glucose to lactic acid, with the net energy gain of two molecules of ATP."
https://www.ncbi.nlm.nih.gov/books/NBK9841/

Your explanation  does not take into consideration that :

at three points, all outside the metabolic pools, do we find reactions in gluconeogenesis that use different enzymes:

https://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/gluconeo.htm
(1) the conversion of pyruvate to phosphoenolpyruvate (PEP),
(2) the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate, and
(3) the conversion of hexose phosphate to storage polysaccharide or hexose phosphate to glucose.


Clearly, if cells are to conduct these reactions in the reverse direction, the three reactions must have a different ATP-to- ADP  Stoichiometry and accordingly different enzymes are required.

Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from the breakdown of proteins ,these substrates include glucogenic amino acids (although not ketogenic amino acids); from breakdown of lipids (such as triglycerides), they include glycerol (although not fatty acids); and from other steps in metabolism they include pyruvate and lactate.

Questions:
If Gluconeogenesis came first, where did the atp and all other  essential products to make enzymes  come from to make the enzymes in the gluconeogenesis pathway ?
Prior Glycolysis took over, what other pathway would supposedly have been  in place to produce the same substrates as Glycolysis ?
What was in your view the precursos of gluconeogenesis?  
Why would Gluconeogenesis be a less chicken egg - catch 22 problem ? Its complexity is basically the same as of Glycolysis.
If the problem of Glycolysis first was the fact that no Glucose was readily available on early earth, what makes you think, the above mentioned substrates to feed gluconeogenesis were less a problem ?
Does Gluconeogenesis not depend on  mitochondria, the cytoplasm, and the cell membrane amongst other molecules ?
Had pyruvate carboxylase and acetyl-CoA not have to be present for gluconeogenesis to start ?
How did the transition from the 3 enzymes used in Gluconeogenesis to Glycolysis occur, and upon what selective pressures ?
Why would there have been a transition from a supposed precursor system to Glycolysis ?

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Trying to educate a creationist (Otangelo Grasso)


http://sandwalk.blogspot.com.br/2017/02/trying-to-educate-creationist-otangelo.html#more

Laurence:
You can reject biochemistry if you like but let's make sure it's correct biochemistry that you are rejecting.

Answer:
I do not reject biochemistry. Actually, almost all the premises of my arguments are based on mainstream scientific papers. What i reject, are just so superficial fairy tale stories in regard of origins based on blind faith and wishful thinking that do not withstand scrutiny, once we dig a little deeper. Will you adopt the same behavior, that you demand from me, Larry ? Will you correct your views, if, once they are exposed as not compelling and demanding ? Because, all you have done so far,  is running away once you were at a road without end, ignored the exposed facts, and  played chess like a pigeon — it knocks the pieces over, craps on the board, and flies back to its flock to claim victory. And now, to the list of all things you called me previously, amongst it to be a liar, plagiarizing, ( despite the fact that all my sources are referenced ) , spreading misinformation, intellectual dishonesty etc, i am also a Dunning Kruger. Nice...... 

Critizism about the opponents knowledge
http://reasonandscience.heavenforum.org/t2114-personal-attacks#3759

Critizising the oponents knowledge, intelligence or education is not the best way to establish a point. I hear often critiques like : You need basic understanding in science, you don't understand evolution, take a science class, we're trying to educate you, you are spouting ignorance of the subject,  you refuse to learn, head well and truly in the sand, willful ignorance is your decision, you don't understand what you're copying and pasting, or go over to explicit insults of various forms and degrees. Mock and ridicule  with contempt is not new. That are responses put forward frequently by Atheists in the attempt to hide their own ignorance, and avoid providing substance. Rather than address the specific issues in question, and provide compelling scenarios that would underline their own views, they resort to  personal attacks and try to discredit the oponent. Not only does it hide their ignorance on the subject, but they expose also their ignorance of their oponents knowledge and education, which cannot be known after a few sentences and posts made on  a specific topic.   Fact is, even IF their oponent were ignorant on the issue, that would not make their  views become more credible or correct. Thats a logical fallacy. The best way for them to deal with the arguments brought forward by proponents of ID/creationism, is:

1. Study if the premise is true. Take the time to actually understand what it is about.
2. Analyse if a compelling case through naturalism exists ( can the origin of the phenomena in question be explained convincingly , proposing natural mechanisms ? )  
3. Analyse if the action of a intelligent, causal agency is not a better explanation
4. If you think , natural unguided,  random or physical or biochemical interactions have  better explanatory power, refute claims of ID proponents, and listen to their defense, or
5. Admit ID has the better explanatory power, and check if that is the case in regard of other issues as well.
6. If various issues are better explained through ID, change your world view, or on the contrary, if naturalism hase a overall more compelling case, keep your world view.  

http://sandwalk.blogspot.com.br/2017/02/trying-to-educate-creationist-otangelo.html


Laurence Moran wrote:
There are bacteria that do not have the standard glycolytic pathway.

Lets recapitulate : 
You said at your article: Pyruvate dehydrogenase astonishes Ann Gauger , following:

More simple versions of this enzyme exist in bacteria suggesting strongly that the complex version in mammals evolved from a simpler version and there may be even more simple versions in other bacteria.

Upon that claim, i wrote at Facebook:
Cells require ATP to manufacture enzymes before glycolysis can even occur. (The old adage of “it takes money to make money” is applicable here—it takes energy to produce energy!) As such, proponents of naturalism have an enormous chicken-egg problem. Which came first, glycolysis to make energy or energy from glycolysis needed to make enzymes?

Laurence Moran:
There are many species of bacteria that do not have the typical glycolytic pathway but all of them have the pathway for gluconeogenesis - the synthesis of glucose.

answer:
Gluconeogenesis is a pathway consisting of a series of eleven enzyme-catalyzed reactions. The pathway may begin in the mitochondria or cytoplasm (of the liver/kidney), this being dependent on the substrate being used. Many of the reactions are the reverse of steps found in glycolysis.
You cannot get around the fact which i mentioned already: Whatever first pathway you replace glycolysis with, it has to be a complex multi-step process , requiring a number of enzymes and regulation. And you will ALWAYS be confronted with the initial problem exposed : it takes energy to make energy. If Gluconeogenesis came before or not, does not change anything in that fundamental problem.

Laurence Moran:
What this shows is that Otangelo didn't listen to a thing I said about basic biochemistry and how scientists understand the origin of life.

answer:
No. What my study showed, is, that science has not credible explanation of how the transition from supposed non enyzmatic, chemical random reactions, to a version using enzymes to make glucose happened:

A paper reports that Fe(II) was broadly available before oxygenation of the early Earth, implying a scenario for the first glycolytic enzymes being simple iron-binding RNA or oligopeptide molecules, which would have possessed the potential of enhancing many reactions now found in central metabolism.  Another paper reports :
 One of the difficulties in describing the origin of metabolism is the fact that the metabolic network is largely composed of intermediates that are not characterized by long‐time stability, at least when considering geological environments and timescales. As shown here and previously, this in particular applies to sugar phosphate molecules [(Larralde et al, 1995). In addition, large sugar phosphates are not frequently generated in experiments that address scenarios of primordial carbon fixation (Cody, 2000; Fuchs, 2011; Hügler & Sievert, 2011).

One must get a picture of the hudge gap from "simple iron-binding RNA or oligopeptide molecules" to a complex metabolic pathway in a thermodynamically up reaction, using ten enzymes , handing one substrate to the next enzyme doing the correct reaction to get the right substrate ( which has by itself in many cases no function ) , handing it over to the next enzyme, and that ten times. And the whole process strictly regulated by other complex mechanisms.

So your "explanation" is actually a strawman, a NO-explanation. A fairy tale story at best. 

That equals to the following scenario: On the one side you have a intelligent agency based system of irreducible complexity of tight integrated , information rich functional systems which have ready on hand energy directed  for such, that routinely generate the sort of phenomenon being observed.  And on the other side imagine a golfer, who has played a golf ball through an 10 hole course. Can you imagine that  the ball could also play itself around the course in his absence ? Of course, we could not discard, that natural forces, like wind , tornadoes or rains or storms  could produce the same result, given enough time.  the chances against it however are so immense, that the suggestion implies that the non-living world had an innate desire to get through the 10 hole course.

Another example to illustrate the problem is as follows : Imagine a production line where pistons for a car engine are produced in ten manufacturing steps. At each step, a complex machine will advance a production step . That intermediate production stage will produce a unfinished pistion, which has by itself no function. At all other nine production steps, the piston is not finished, and has no function. Once the whole production steps are gone through, you have a finished piston. What function does that piston have, if not mounted inside the motorblock, fitting correctly inside the cylinder, with the righ tolerances, correctly interlinked to exercise its function ?

In the cell, these processes happen in a complex production process, similar to a factory, with many interlinked compartments, all connected and interacting together in a complex manner. For this to happen in a coordinated and orderly and controlled manner, intelligent planning is indispensable. I have written in detail about the procedure, drawing comparisons of human made factories, to cell factories :

Factory and machine planning and design, and what it tells us about cell factories and molecular machines
http://reasonandscience.heavenforum.org/t2245-factory-and-machine-planning-and-design-and-what-it-tells-us-about-cell-factories-and-molecular-machines

Genome information, protein synthesis,  the biosynthesis pathways in biologiy, and the analogy of human programming, engeneering, and factory robotic assembly lines
http://reasonandscience.heavenforum.org/t1987-information-biosynthesis-analogy-with-human-programming-engeneering-and-factory-robotic-assembly-lines

The best and most advanced result that  intelligent  and capable  minds, thousands and hundred thousands of the most brilliant and inventive man and woman from all over the globe have been  able to come up with after over one hundred years of technologic advance and progress, of what is considered one of the greatest innovations of the 20th century , is the construction of complex factories with fully automated assembly lines which use  programmed roboters in the manufacturing, assembly, quality control and  packing process of the most diverse products, in the most economic, efficient and effective way possible,  integrating  different facilities and systems, and using advanced statistical methods of quality control, making  from cell phones, to cars, to power plants etc.,  but the constant intervention of intelligent brain power is required to get the whole process done, and obtain  the final products. The distribution of the products is also based on complex distribution networks and companies, which all require hudge efforts of constant human intervention and brainpower.  

Amazingly, the highest degree of manufacturing  performance, excellence, precision, energy efficiency, adaptability to external change, economy, refinement and intelligence of production automatization ( at our scale = 100 )  we find in proceedings adopted by  each cell,  analogous to our factory , and biosynthesis pathways and processes in biology.  A cell uses a complex web of metabolic pathways, each composed of chains of chemical reactions in which the product of one enzyme becomes the substrate of the next. In this maze of pathways, there are many branch points where different enzymes compete for the same substrate. The system is so complex that elaborate controls are required to regulate when and how rapidly each reaction occurs. Like a factory production line, each enzyme catalyzes a specific reaction, using the product of the upstream enzyme, and passing the result to the downstream enzyme. If just one of the enzymes is not present or otherwise not functioning then the entire process doesn’t work. We now know that nearly every major process in a cell is carried out by assemblies of 10 or more protein molecules. And, as it carries out its biological functions, each of these protein assemblies interacts with several other large complexes of proteins. Indeed, the entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines.Cells adopt highest advanced Mass-Craft production techniques , which yeald products with the ability of high adaptability to the environment ( micro evolution ) while being produced with high efficiency of production, advanced error checking mechanisms, low energy consumption and automatization, and so being generally being  far far more advanced, complex,  better structured and organized in every aspect, than the most advanced robotic assembly facility ever created by man. Unlike our own pseudo-automated assembly plants, where external controls are being continually applied, the cell's manufacturing capability is entirely self-regulated . . . . I advocate that this fact is strong evidence of a planning, super intelligent mind, which conceptualized and created  life right from scratch.

Considerations of the planning of the layout of a assembly line facility.

Important considerations for a high economic,  effective and proper material flow are required and must be considered, thought and brought in when planning the concepts and layout design of a new factory assembly line, as for example maximal  flexibility in the line for demand and supply fluctuation,  planning  deep enough to answer all possible aspects of a new line to get max efficiency afterwards.   There should be simple material delivery routes and pathways throughout the facility that connect the processes. Also, there needs to be a plan for flexbility and changes, since volumes and demand are variable. Awareness of the many factors involved right in the planning process of the factory is key. Right-sized equipment and facilities must be planned and considered as well. All equipment and facilities should be designed to the demand rate or takt timeProjects and facility designs  that do not take these considerations in account,  start out great, but quickly bog down in unresolved issues, lack of consensus, confusion and delay.

Larry wrote:
He didn't like the fact that I have been ignoring him for the last few days so he posted a comment on Sandwalk.

Answer:
Correct. I qualify that as rude behavior, which does the other part not grant a adequate answer upon the effort made to elucidate the case, and elucidate the case till the end.
Is that not ALWAYS what you do, Larry ? Check and see, on how many issues you silenced and vanished from the debate, since your case was unmasked for what it is : superficial just so stories without real arguments and explanations to back up the case. Happened with the case of the spliceosome, and here another case :

Some fun at Larrys blog
http://reasonandscience.heavenforum.org/t2384-some-fun-at-larrys-blog

Laurence Moran :
The original glycolytic pathway began with glucose-6-phosphate produced from the breakdown of glycogen.

Answer:
Glycogen Synthesis : For de novo glycogen synthesis to proceed the first glucose residue is attached to a protein known as glycogenin.
http://themedicalbiochemistrypage.org/glycogen.php

So to have glycogen as substrate, you need glucose. So we are back to the same question : Where did glucose come from in early earth ?

Laurence Moran:
Knowledgeable biochemists assume that the first cells made glucose by fixing CO2

There were no cells at the beginning. But glucose was needed ( or, as you assert above, glycogen ) as source to produce energy.....

My question:
If Gluconeogenesis came first, where did the atp and all other essential products to make enzymes come from to make the enzymes in the gluconeogenesis pathway?

Larry answers :
Chemoautotrophs exist and so do plants. your question is ridiculous because there are obviously many ways to make ATP that have nothing to do with glycolysis. All you need to do is learn about them.

Answer:
Had you read my article above with attention, you would have observed that i addressed this subject, and posted why it is not a solution:
At point 3, about Chemisynthesis, i posted:

Chemisynthesis is employed by organisms that live in the environment around deep-sea volcanic vents, where hot, hydrogen sulfide-rich waters pour out of newly formed ocean crust Such waters, compared to the colder, sulfide-poor adjacent regions, have an abundant supply of free energy. This term refers to a source of energy that can be utilized readily to do some form of work, such as sustain biological processes, or can be stored in high-energy phosphate bonds. One readily available means to extract energy from the vents is to combine hydrogen sulfide with oxygen to form sulfur dioxide with production of energy. Such a process is possible in an ocean that has free oxygen available, but would not work on the primitive, pre-oxygen-rich Earth. Other biochemical cycles that use sulfur but not oxygen are conducted by some prokaryotic organisms, but these capture much less energy than the oxygendriven cycles. As with fermentation, chemisynthesis without free oxygen was the hallmark of a rather sluggish primitive biota.

Laurence :
you refuse to accept any origin or life scenario that doesn't require gods. That's fine, I just want to stop you from spreading nonsense about biochemistry on the internet.

Answer:
I can say the same ( and thats all you actually show ): you refuse to accept any origin or life scenario and world view involving a intelligent agency. So far, Larry, it was not me. It was you abandone each case study, always, when you felt you were unable to explain the issue in question with evolution, and you had no way to provide a better answer than scream: " evolution did it ". Again: What issue in the last two years you proved me wrong, and it would have been the right thing to do, is to correct the information at my library? Can you show even now ONE issue that is portrayed in a false , misleading manner at my library ?

In contrast, as i characterised your modo operandi at my facebook timeline:

Laurence A. Moran 's modo operandi is as follows. Make claims about the heroic achievements of evolution as the all powerful mechanism to explain biodiversity. His elected deserver of a diamond medal for the special achievements is genetic drift. Back up the claims with technical terms used in biology that are not common knowledge, but enough impressive for his guillible audience to swallow. Remain always obtuse. Don't digg deep, remain on the safe shallow waters of superficial explanations and assertions, that give always enough room to insert in the gap of knowledge evolution. Scream loud enough about how brainless, stupid and deluded IDiot's are. Do never admit that the counterpart has a case worth to be considered. Let his followers at his blog name call ID proponents as much as they want. Thinks he has a case...

My question:
If the problem of Glycolysis first was the fact that no Glucose was readily available on early earth, what makes you think, the above mentioned substrates to feed gluconeogenesis were less a problem?
Laurence:
Because there was always a good supply of CO2 on Earth.
Answer:
So what? you mentioned glycogen as alternative, which, as already answered , is a strawman answer.

My question:
Does Gluconeogenesis not depend on mitochondria, the cytoplasm, and the cell membrane amongst other molecules?
Laurence:
It certainly doesn't depend on mitochondria! The fact that you ask such a question shows me that you absolutely refuse to listen to anything I say.
If you are willing to accept everything I've said above and correct your Facebook pages and your website pages, then we can discuss the rest of your question. I can't do that knowing that you probably won't listen to anything I say.
Answer:
My question is based on what following paper states:
Gluconeogenesis is a pathway consisting of a series of eleven enzyme-catalyzed reactions. The pathway may begin in the mitochondria or cytoplasm (of the liver/kidney), this being dependent on the substrate being used.
https://en.wikibooks.org/wiki/Principles_of_Biochemistry/Gluconeogenesis_and_Glycogenesis

Laurence:
I don't know how those two enzymes arose.
Answer:
You don't know how these two enzymes emerged. What about all others used in Gluconeogenesis, and Glycolysis ? lol.....

Bill Faint : The vast majority are rude, insulting, arrogant, vulgar, provocative etc. You are delusional about your camp, though I have built a good relationship with a handful who don't immediately resort to name calling, personal attacks, filthy memes and overtly aggressive postures, and for these few I am grateful. Not all atheists have a superiority complex

The vast majority are rude, insulting, arrogant, vulgar, provocative etc. resort to name calling, personal attacks, and overtly aggressive postures.  Not all atheists have a superiority complex



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The odds of forming the glycolysis or the gluconeogenesis pathway by chance


The sequence of chemical reactions which, on the prebiotic Earth, led to the formation of the chemical building blocks of life, must also have included phosphorylation reactions. As mentioned in the Introduction, there are two major hurdles to be overcome in creating a model of prebiotic phosphorylation - the problem of energy source and the problem of concentration. 3 Phosphorylation, the conversion of orthophosphate into organic phosphates, is thermodynamically very unfavorable in the presence of an excess of water.

Substrate-level phosphorylation
The first substrate-level phosphorylation occurs after the conversion of 3-phosphoglyceraldehyde and Pi and NAD+ to 1,3-bisphosphoglycerate via glyceraldehyde 3-phosphate dehydrogenase. 1,3-bisphosphoglycerate is then dephosphorylated via phosphoglycerate kinase, producing 3-phosphoglycerate and ATP through a substrate-level phosphorylation. The second substrate-level phosphorylation occurs by dephosphorylating phosphoenolpyruvate (phosphoenolpyruvic acid), catalyzed by pyruvate kinase, producing pyruvate and ATP. During the preparatory phase, each 6-carbon glucose molecule is broken into two 3-carbon molecules. Thus, in glycolysis dephosphorylation results in the production of 4 ATP. However, the prior preparatory phase consumes 2 ATP, so the net yield in glycolysis is 2 ATP. 2 molecules of NADH are also produced and can be used in oxidative phosphorylation to generate more ATP.


We note that Stanley Miller's experiments only produced 13 of the 21 basic (amino acid) building blocks of protein molecules. 2 To put this in perspective, lets assume that a modern computer running Windows Vista, with Monitor and Printer, and plugged into an electric source of power is comparable to the most basic self-replicating bacterium. Let's also assume that the Computer system consists of 21 basic materials (i.e. gold, silver, aluminum, tin, lead, silicon, plastic, etc...). Then what Miller found is equivalent to finding 13 of the 21 basic materials with which "computers" are made of. But even if we had all 21, we still need to order them ALL into the correct pieces (i.e. wire, solder, plastic frame, screws, circuit boards, Integrated Circuits, fan, Power Supply, smooth glass, etc..) --- something that simply WILL NOT happen all by itself. This is one of the many reasons why more and more people today are turning to Intelligent Design, as the evidence clearly indicates that God (or an outside Intelligent Influence) must have intervened in the Creation/Origin of Life on this Planet.

Proteins, for example, consist of long chains of 400 or more amino acids in a specific sequence. 1 Each of the amino acids in the sequence is one of 20 different kinds, and if the sequence is altered slightly, the protein will not be functional.  Moreover, 19 of the 20 kinds of amino acids[2] come in two forms—a left-handed and a right-handed form—but living things consist only of left-handed molecules.  Outside of living things, amino acids occur only in a 50-50 ratio of right-handed and left-handed forms.  Even if we artificially create a sample where one form or the other predominates, the sample will, with time, return to a 50-50 ratio through a process called racemation.

The odds of 400 left-handed amino acids linking up by chance is less than (0.5)380, and, since the simplest cell would need over 120 proteins, the combined probability would be less than (0.5)380x120 = 1.08x10-13,727.  This is an impossibly small probability, and we have not yet accounted for the specific sequences of amino acids needed, which would reduce the probability far more.[3]

The probability of getting heads in a single flip of a fair coin is 1 in 2. The probability of getting four heads in a row is 1/2 × 1/2 × 1/2 × 1/2, that is, (1/2)4 or 1/16.

For the occurrence of two particular nucleotide bases, the odds are 1/4 × 1/4. For three, 1/4 × 1/4 × 1/4, or 1/64, or (1/4),3 and so on.  The information-carrying capacity of a sequence of a specific length n can then be
calculated using Shannon’s familiar expres​sion(I =–log2p) once one computes a probability value (p) for the occurrence of a particular sequence n nucleotides long where p = (1/4)n. The p value thus yields a corresponding measure of information-carrying capacity or syntactic information for a sequence of n nucleotide bases.

Lets apply the same calculation to glycolysis:

1.Hexokinase 915 amino acids : (0.5)732 
http://www.brenda-enzymes.info/sequences.php?f[stype_ec]=1&f[ec]=2.7.1.1&f[stype_accession_code]=1&f[accession_code]=Q91W97
2.Phosphoglucose isomerase 569 amino acids (0.5)455
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=5.3.1.9&f[stype_accession_code]=1&f[accession_code]=P29333
3.Phosphofructokinase 941 amino acids (0.5)752
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=2.7.1.11&f[stype_accession_code]=1&f[accession_code]=C4QXA5
4.Fructose-bisphosphate aldolase 364 amino acids (0.5)291
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=4.1.2.13&f[stype_accession_code]=1&f[accession_code]=Q8JH71
5.Triosephosphate isomerase 241 amino acids (0.5)193
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=5.3.1.1&f[stype_accession_code]=1&f[accession_code]=B0CEX1
6.Glyceraldehyde 3-phosphate dehydrogenase 336 amino acids (0.5)269
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=1.2.1.12&f[stype_accession_code]=1&f[accession_code]=P17729
7.Phosphoglycerate kinase 417 amino acids (0.5)334
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=2.7.2.3&f[stype_accession_code]=1&f[accession_code]=P00559
8.Phosphoglycerate mutase 404 amino acids (0.5)323
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=5.4.2.1&f[stype_accession_code]=1&f[accession_code]=Q2Y4T5
9.Enolase 432 amino acids (0.5)345
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=4.2.1.11&f[stype_accession_code]=1&f[accession_code]=Q74K78
10. Pyruvate kinase 508 amino acids (0.5)406
http://www.brenda-enzymes.org/sequences.php?f[stype_ec]=1&f[ec]=2.7.1.40&f[stype_accession_code]=1&f[accession_code]=Q6FV12

So the average size of each protein is about 512 amino acids. (0.5)512 x 10  or (0.5)5120  or one to 10^10240




While most steps in gluconeogenesis are the reverse of those found in glycolysis, three regulated and strongly exergonic reactions are replaced with more kinetically favorable reactions.

1. Hexokinase/glucokinase, ====  glucose-6-phosphatase,
3. phosphofructokinase, =====  fructose-1,6-bisphosphatase,
10. pyruvate kinase enzymes ======  PEP carboxykinase

glucose-6-phosphatase
http://www.brenda-enzymes.org/enzyme.php?ecno=3.1.3.9&showtm=0&onlyTable=Sequence

This system of reciprocal control allow glycolysis and gluconeogenesis to inhibit each other and prevent the formation of a futile cycle.

That means, both exist in parallel, together.

The majority of the enzymes responsible for gluconeogenesis are found in the cytoplasm; the exceptions are mitochondrial pyruvate carboxylase and, in animals, phosphoenolpyruvate carboxykinase. The latter exists as an isozyme located in both the mitochondrion and the cytosol.

Than means, mitochondria is required by the gluconeogenesis pathway. 


Right here there is a major problem for chemical soup approaches to the origin of life: all the components have to be present in the same location for a living cell to have any possibility of being assembled. 4 But necessary components of life have carbonyl (>C=O) chemical groups that react destructively with amino acids and other amino (–NH2) compounds. Such carbonyl-containing molecules include sugars,4 which also form the backbone of DNA and RNA. Living cells have ways of keeping them apart and protecting them to prevent such cross-reactions, or can repair the damage when it occurs, but a chemical soup has no such facility.

Some sugars can be made just from chemistry without enzymes (which are only made by cells, remember).  However, mechanisms for making sugars without enzymes need an alkaline environment, which is incompatible with the needs for amino acid synthesis.The chemical reaction that is proposed for the formation of sugars needs the absence of nitrogenous compounds, such as amino acids, because these react with the formaldehyde, the intermediate products, and the sugars, to produce non-biological chemicals.Ribose, the sugar that forms the backbone of RNA, and in modified form DNA, an essential part of all living cells, is especially problematic. It is an unstable sugar (it has a short half-life, or breaks down quickly) in the real world at near-neutral pH (neither acid nor alkaline)

Sugars have linear forms that contain carbonyls—see Fig. 2.



The cyclic forms that occur in nucleic acids also predominate in solution form, but in equilibrium with the linear form. When something reacts strongly with the aldehyde, then more of the linear form is regenerated to replace that which is reacted, so all the sugar molecules will be consumed


1. http://members.toast.net/puritan/Articles/HowOldIsTheEarth_A.htm
2. http://creationwiki.org/The_odds_of_life_forming_are_incredibly_small_(Talk.Origins)
3. The Origin 01 Lite and Evolutionary Biochemistry page 177
4. http://creation.com/origin-of-life



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Gluconeogenesis 2

With the exception of reactions catalyzed by phosphofructokinase and pyruvate kinase, glycolytic reactions are reversible and function also in gluconeogenesis (Figure 7.2). The reversal of the latter reaction, i.e. conversion of pyruvate into phosphoenolpyruvate, can be catalyzed by two c10sely related enzymes, phosphoenolpyruvate synthase and pyruvate,phosphate dikinase. The only other reaction that is specific for gluconeogenesis is the dephosphorylation of fructose-1 ,6-bisphosphate.

Phosphoenolpyruvate synthase (EC 2.7.9.2)
Phosphoenolpyruvate synthase (pyruvate, water dikinase, EC 2.7.9.2)
and pyruvate, phosphate dikinase (EC 2.7.9.1) catalyze two similar reactions of phosphoenolpyruvate biosynthesis

Pyruvate + ATP + H20 = Phosphoenolpyruvate + AMP + Pi
Pyruvate + ATP + Pi = Phosphoenolpyruvate + AMP + PPi

and have highly similar sequences. This enzyme is widely present in bacteria, archaea, protists and plants, but is missing in animals, where PEP is synthesized from oxaloacetate in a PEP carboxykinase-catalyzed reaction.

Phosphoenolpyruvate carboxykinase (EC 4.1.1.32 and EC 4.1.1.49) Phosphoenolpyruvate carboxykinase exists in two unrelated forms, which catalyze ATP-dependent (EC 4.1.1.49) or GTP-dependent (EC 4.1.1.32) decarboxylation of oxaloacetate:

Oxaloacetate + ATP = Phosphoenolpyruvate + ADP + CO2
Oxaloacetate + GTP = Phosphoenolpyruvate + GDP + CO2

These forms show remarkably complex phyletic distributions. The GTP dependent form is found in animals and in a limited number of bacteria, such as Chlamydia spp., Mycobacterium spp., T. pallidum, and the green sulfur
bacterium Chlorobium limicola. Among archaea, it is encoded only in the genomes of pyrococci, thermoplasmas, and Sulfolobus. In contrast, the ATPdependent form of phosphoenolpyruvate carboxykinase is found in plants,
yeast, and many bacteria. The only complete archaeal genome that has been found to encode the ATP-dependent form is that of A. pernix (Figure 7.2).

COMPARATIVE GENOMICS, MINIMAL GENE-SETS AND THE LAST UNIVERSAL COMMON ANCESTOR 1



(Figure 7.2)


1. http://www.cbs.dtu.dk/CBS/courses/brazilworkshop/files/koonin_NRM_2003.pdf
2. SEQUENCE - EVOLUTION - FUNCTION Computational Approaches in Comparative Genomics, page 303, Koonin

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Its entirely pointless to argue if 500, or 200 genes are required to get a first living cell. Whatever number you put, and upon the fact that number of life essential things are required, you have the minimal, not further reducible cell. Subunits or parts like a piston in a car engine are only designed, when there is a goal where they will be mounted with specific fitting sizes, and correct materials, and have a specific function in the machine as a whole. What good is a ribosome without mRNA, tRNA, error correction, a cipher to be translated, and ATP energy supply ? No function at all. Thats a cell factory requires forplanning to be setup.



Photosynthesis

Your so called progenote that supposedly came prior to LUCA could not be simple.

The universal ancestor

http://www.pnas.org/content/95/12/6854.full

The Archaea and Bacteria share a large number of metabolic genes that are not found in eukaryotes. If these two “prokaryotic” groups span the primary phylogenetic divide and their genes are vertically (genealogically) inherited, then the universal ancestor must have had all of these genes, these many functions. This distribution of genes would make the ancestor a prototroph with a complete tricarboxylic acid cycle, polysaccharide metabolism, both sulfur oxidation and reduction, and nitrogen fixation; it was motile by means of flagella; it had a regulated cell cycle, and more. This is not the simple ancestor, limited in metabolic capabilities, that biologists originally intuited. That ancestor can explain neither this broad distribution of diverse metabolic functions nor the early origin of autotrophy implied by this distribution. The ancestor that this broad spread of metabolic genes demands is totipotent , a genetically rich and complex entity, as rich and complex as any modern cell—seemingly more so.

All these functions are ENORMOUSLY complex.

I don't believe there was no Progenote, nor LUCA. I believe Genesis is true. I am a creationist by all means, and see good reasons to held this view.


Photosynthesis

the article is about a universal ancestor, that gave rise to luca. Since there are hudge differences between eukaryotes and prokaryotes, this supposed ancestor would have to incorporate both, genes to give rise the archea and prokaryotes, and eukaryotes as well.

LUCA is anyway a buried concept. Evidence does not point to a universal common ancestor.

Prokaryotic evolution and the tree of life are two different things

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761302/

The concept of a tree of life is prevalent in the evolutionary literature. It stems from attempting to obtain a grand unified natural system that reflects a recurrent process of species and lineage splittings for all forms of life. Traditionally, the discipline of systematics operates in a similar hierarchy of bifurcating (sometimes multifurcating) categories. The assumption of a universal tree of life hinges upon the process of evolution being tree-like throughout all forms of life and all of biological time. In prokaryotes, they do not. Prokaryotic evolution and the tree of life are two different things, and we need to treat them as such, rather than extrapolating from macroscopic life to prokaryotes.



Photosynthesis

rather than make lame and pointless acusations about dishonesty, what about you give honest thought about the fact that the the minimal cell, whatever it was, no matter if it had 100, 200, or 500 genes, was irreducible complex ?
I made some very specific questions, what about you answer them ?
And since we are at it, have you ever thought about the evidence that you expect to observe in the natural world to acknowledge design as the best explanation of origins ?
If you never thought about it : Why do you look at the speck of sawdust in my eye and pay no attention to the plank in your own eye?


photosynthesis

Yes, i have a topic at my library:

From the first living organism OOL to to the last universal common ancestor (LUCA)

you will find there following:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2478661/
LUCA may be understood as a diverse community of already metabolically and genetically sophisticated organisms. Its predecessor the progenote, more primitive and modular, was also a heterogeneous and diverse community of cells engaged in the emergence of a genetic code. The emergence of self-replicating entities of increasing complexity requires both the formation of compartments (without which no distinction can be made between genotype and phenotype, and parasitic molecules can not be removed) and an ambient metabolism from which to draw renewable building blocks; such a metabolism therefore should be self-sustaining to a certain extent.

What is your point ? Feel free to consider and answer my questions above now.





photosynthesis wrote

"You quoted something that says they're different, but I cannot know if you understand that at all "

In other words, you question my intelligence and hability of understanding. Bill Fait at my FB timeline gave a nice characterisation of common  atheist behavior :
The vast majority are rude, insulting, arrogant, vulgar, provocative,  resort to name calling, personal attacks, and overtly aggressive postures. Most atheists have a superiority complex.

Your posts, photosynthesis, are no exception.

"since you seem unable to articulate the difference yourself. Yet, that's a bit of progress."

I am not only not able to articulate the difference myself. I have NO CLUE AT ALL HOW THAT SUPPOSED PROGENOTE should have looked like. And guess what ? Neither so have scientists. Neither so you do. The paper from where i quote HAS NO REAL CLUE either.
But you think you have ? If so, what about you give a precise characterisation based on hard scientific data and research ?!


"If you do understand the difference, then the point is that now you should be able to renounce to quotes about LUCA as if they represented the first life forms. Right? "

No, not right. Nobody  knows  if there was such a transition. Obviously, proponents of evolution try to insert evolution everywhere in their gap of understanding, in order to keep their blind faith that " Nothing in Biology Makes Sense Except in the Light of Evolution ".  Its nothing more than guess work and speculation.

" Sorry, but you cannot call that a fact. For one, your "fact" is a guess based on misquoting articles about potential LUCAs. For another, to prove that the first life forms was irreducibly complex, you'd have to know the factors involved in its origin, what it was really like, and that it could not have evolved or arisen naturally at all. With so many unknowns, I would not be so hasty to claim that it's a fact that the first life forms were irreducibly complex. (I'm talking about the "it could not have evolved at all" version of IC.)"

Denial of the obvious  to keep your no-God-ideology , wear eye and ear gards, and throw lame acusations about dishonesty ?!!
We know that even one protein  could not have emerged by natural means. Ribosomes, mRNA, tRNA's, error check and repair, ATP,  tRNA synthetases and the genetic code are irreducible and interdependent. One alone has no use, only all together. Its not difficult for anyone with a little understanding of biology to " get" that.   HONEST thinkers come to that conclusion  without much effort. But your wilful ignorance exposes your bias and bad will. Thats why you are an atheist.

"I don't know who everything evolved. I know general approaches, bits of answers here and there, but I don't know everything."

Yep. Its enough to know that God is not required. Got ya.

"And since we are at it, have you ever thought about the evidence that you expect to observe in the natural world to acknowledge design as the best explanation of origins ?"
I haven't. "

Congrats. Thats a answer that i know you are telling the truth.

" But I think that if we considered designers, then we would not be talking about origins, right? After all, if there was designers, then how did these designers originate? Where did they come from? What tools did they use? Where they designed or the result of some natural phenomena? What kinds of phenomena? We would be left where we started. "

So here you make irrelevant questions to deflect from the real ones : Namely why chance would be a better explanation than design....

"What plank? I have no reason to consider designers."

Have you searched ? No. By your own admission. You have not even given a thought about what would be signs of intelligence. A hint.  Self replicating information rich factories full of complex machines and manufacturing production lines, information flow of encoding, transmitting, and decoding of codes, information, and language are *always* a deliberate act of intelligence. All that you find in every living cell.


photosynthesis wrote

"I did not ask you what a progenote looked like at all. I asked you if you know the difference between the concept of a LUCA and that of a first life form. You obviously don't. Not only that, you don't have the honesty to try and understand it."

I answered your question above with a quote from a scientific paper. But you keep acusing me of not knowing the difference. Who is being dishonest by repeating a question which i answered already ? And if you think my answer was not correct, why do you not simply correct me ? Ahhh... just in order for keeping your lame acusations ?

"If, at the very least, you knew that they're not the same thing, you'd understand why you should stop using quotes about the LUCA as if they were meant to represent original life."

I answered already. NOBODY KNOWS if there was such a transition. I don't buy the story at all. For me, phyla were created by God. As we read in Genesis. And from there, the different life forms diverged and adapted to the environment.

"That doesn't mean that articles about the LUCA can be misused as if they referred to the original life. You don't want to be called a fool, yet you argue as one. What else are we left to think about you?"

You are not understanding in order to be able to name call me. For sake, give a try in advancing  your education and stop insulting the counterpart you debate with. I repeat , and say it again : It makes no difference, if first life had 500, 200, or 100 genes. Whatever you put as first life was irreducible complex.

"What do you mean by obvious? You refuse to understand a simple distinction, and it's me who denies the obvious? Larrry is right, you're uneducable."

Did i entitle you to educate me ? Your superiority complex shines through nicely....

"We know that even one protein could not have emerged by natural means."
We don't know such a thing. "

We absolutely do. Thats the kind of things anyone is able to understand. But you are unwilling, and that is your problem.


"Given that you cannot understand how mistaking the concepts of LUCA and original life is problematic, I doubt that your can claim to know such a thing at all. I've seen your quotes, and they show deep ignorance and will for misrepresentation. Not knowledge."

Yep. Keep your eye and ear gards firmly weared.....

"Ribosomes, mRNA, tRNA's, error check and repair, ATP, tRNA synthetases and the genetic code are irreducible and interdependent"
In some cases, in some organisms, maybe."

No kidding...... In what organism does ANY of the mentioned parts function without the others ?

" But that doesn't mean that they could not have evolved. It just means that they're independent in their current form and situation. "

They could not have evolved because dna replication depends on these parts, and evolution depends on DNA replication.
Who is in need here of a basic education in biology ?

"If you were asking me to consider fantasies, then you should have said so. That's easier to answer: I don't consider fantasies because, well, they're fantasies. See how easy that was? "

Humm... Fantasies ? Sure. One day, we will see......

"Irrelevant questions? So, to consider designers we should not wonder about the designers themselves? Their methods, their tools, their origins?And that's reasonable? Your standards are very weird. For nature, you want each and every detail. For "designers" you don't care about details at all. Isn't that a bit hypocritical? "

No, its not.

W.L.Craig :
First, in order to recognize an explanation as the best, one needn't have an explanation of the explanation. This is an elementary point concerning inference to the best explanation as practiced in the philosophy of science. If archaeologists digging in the earth were to discover things looking like arrowheads and hatchet heads and pottery shards, they would be justified in inferring that these artifacts are not the chance result of sedimentation and metamorphosis, but products of some unknown group of people, even though they had no explanation of who these people were or where they came from. Similarly, if astronauts were to come upon a pile of machinery on the back side of the moon, they would be justified in inferring that it was the product of intelligent, extra-terrestrial agents, even if they had no idea whatsoever who these extra-terrestrial agents were or how they got there. In order to recognize an explanation as the best, one needn't be able to explain the explanation. In fact, so requiring would lead to an infinite regress of explanations, so that nothing could ever be explained and science would be destroyed. So in the case at hand, in order to recognize that intelligent design is the best explanation of the appearance of design in the universe, one needn't be able to explain the designer.

"Chance? Who's talking about chance? I'm talking about natural processes, surely you understand that nature is not just chance, don't you? If you do, then why bring such a false dichotomy to the table?"

Neither Evolution nor physical necessity are a driving force prior dna replication :The origin of the first cell, cannot be explained by natural selection (Ann N Y Acad, 2000) DNA replication had  to be previously, before life began, fully setup , working, and fully operating, in order for evolution to act upon the resulting mutations. The  remaining possible mechanisms are chemical reactions acting upon unguided random events ( luck,chance), or physical necessity. It could not be physical necessity, because that would constrain the possible gene sequences, but they are free and unconstrained; any of the bases can be interlinked into any sequence. If design, or physical necessity is excluded, the only remaining possible mechanism for the origin of life is chance/luck.

"See ya Otangelo. You're authentically uneducable."

A true pupill in the foodsteps of Larry.... , ignores the exposed facts, and  plays chess like a pigeon — it knocks the pieces over, craps on the board, and flies back to its flock to claims victory. Congrats.

Ed

the only point i intended to make is that in order to infer design as the best explanation of origins, we do not need to explain the designer. Of course, once that design is the best explanation, a curious mind will go further and ask a serious of philosophical and theological questions, as i point out at the topic which i posted here :  "A cumulative case for the God of the bible". 

A simple syllogism illustrates the rationale:

There are three possible mechanisms of origins, chance, physical necessity, and intelligent design / creation.
Its not chance, nor physical necessity. 
Therefore, ID is the most plausible, adequate explanation of origins. 

Objection: You really need to take time to define who this supreme being is before you can assert  it actually exists. 
Answer: No proponent of Intelligent design makes conclusive absolute assertions that a Intelligent Designer exists. One of the best solutions to handling the issue of evidence and arguments for God’s existence is to utilize what is called inference to the best explanation. The inference to the best explanation model takes into account the best available explanation in our whole range of experience and reflection. Since we as humans can’t observe God as a material object, one way to approach this issue is to look at the effects in the world and make rational inferences to the cause of the effect. Remember, evidence is always evidence for (or against) something.

Ed wrote:

"Just to remind you: "evolution can't do this, thus goddidit" isn't evidence. Which up until now, is in fact the basis of 100% of your arguments."

Well, no. My inferences are based positive evidence. 

http://www.grisda.org/htdocs/origins/Origins%2064%20Full.pdf
To use design as a basis for scientific predictions is compatible with the scientific process ( based on methodological naturalism) because it does exactly what science is supposed to do ( without excluding design as possible causal agency a priori ). It puts our theories and hypotheses out in the open to be discussed, to be supported by accumulating evidence, or refuted by the evidence. Intelligent design theory seeks  evidence of design in nature. ID starts with observation in the natural world, and tries to find out, how the  origin  of given phenomenon can be best explained. Since there are basically two possible mechanisms, design, and natural, unguided, random events, both should be considered, and evaluated against each other.

Communication systems of encoding, transmission and decoding  of coded instructional complex information  found in genetic/epigenetics, and irreducible , interdependent molecular factories,  machines,  and biosynthetic and metabolic pathways in biological systems point to a intelligent agent as best explanation of their setup and origins. 

txpiper

you are right. There might be a mix of chance and physical necessity, but that does not change the fact that there are no other mechanisms.

photosynthesis thinks that "physical necessity" is a brilliant invention of Craig, but its not. As for example we can read about physical necessity at mainstream papers:

http://www.sciencedirect.com/science/article/pii/S0049237X09704124

Its remarkable how people of aparently normal intelligence shut down their logical thinking, and are willing to deny the very obvious in order to keep to their No-God-needed ideology at any cost, even the one to bury the inborn hability of examine the evidence, evaluate it, and let the evidence lead wherever it is. If at the end of the road there is God, it cannot be. God ?!! No no, he is inacceptable.... Bible? No way....

No, even if you mix chance with physical necessity, its impossible to get functional proteins, and even far less so a glycolysis or glyconeogenesis pathway, or for sake a primordial cell by non guided mechanisms.

Koonin admits :

The Logic of Chance: The Nature and Origin of Biological Evolution, Eugene V. Koonin, page 351:
The origin of life is the most difficult problem that faces evolutionary biology and, arguably, biology in general. Indeed, the problem is so hard and the current state of the art seems so frustrating that some researchers prefer to dismiss the entire issue as being outside the scientific domain altogether, on the grounds that unique events are not conducive to scientific study.

A succession of exceedingly unlikely steps is essential for the origin of life, from the synthesis and accumulation of nucleotides to the origin of translation; through the multiplication of probabilities, these make the final outcome seem almost like a miracle. The difficulties remain formidable. For all the effort, we do not currently have coherent and plausible models for the path from simple organic molecules to the first life forms. Most damningly, the powerful mechanisms of biological evolution were not available for all the stages preceding the emergence of replicator systems. Given all these major difficulties, it appears prudent to seriously consider radical alternatives for the origin of life

For example, "chemical reactions acting on random events" is not "physical necessity" alone. It's a mixture.

what about you DO NOT misquote what i wrote ? 

chemical reactions acting upon unguided random events ( luck,chance)

is one thing, and physical necessity. It could not be physical necessity, because that would constrain the possible gene sequences, which is not the case. 

if design is excluded, the alternatives are a) chance, b) physical necessity, or c) a mix of the previous two. 

The gene sequences are not constraint by physical necessity, since any nucleotide sequence is possible. So if you exclude a intelligent agency prodiving the correct sequence, the only alternative is random chance. 

In regard of entropy, txpiper is correct. As my FB friend Bill faint eloquently posted:

" life in any form is a very serious enigma and conundrum. It does something, whatever the biochemical pathway, machinery, enzymes etc. are involved, that should not and honestly could not ever "get off the ground". It SPONTANEOUSLY recruits Gibbs free energy from its environment so as to reduce it's own entropy. That is tantamount to a rock continuously recruiting the wand to roll it up the hill, or a rusty nail "figuring out" how to spontaneously unrust and add layers of galvanizing zinc on itself to fight corrosion. Unintelligent simple chemicals can't self organize into instructions for building solar farms (photo systems 1 and 2), hydroelectric dams (ATP synthase), propulsion (motor proteins) , self repair (p53 tumor supressor proteins) or self destruct (caspases) in the event that these instructions become too damaged by the way the universe USUALLY operates. A biogenesis is not an issue that scientists simply need more time to figure out but a fundamental problem with materialism "

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let’s follow three carbon molecules from the air to three separate destinations. Imagine these molecules enjoying a carefree life as a gas, each accompanied by two oxygen molecules, as they joyride side-by-side through the air without a care in the world. Suddenly, all three smack into a green, leafy something and quickly pass from the bright light of the atmosphere into the dark, vascular world of a plant. Now their carefree existence turns into a wild toboggan ride of photosynthesis. The three molecules go through a series of transformative twists, turns, and drops as they travel through the plant, bathed in green, drenched in water, stripped of their oxygen buddies, and eventually picking up new molecular passengers, including hydrogen, nitrogen, and more carbon. At the end of their wild ride, the molecules are no longer part of a gas having become instead part of a sugary carbohydrate called glucose, a vital source of energy for the plant. At this point a new ride begins and our three carbon molecules are quickly sent in three separate directions. The first molecule concludes its journey in a leaf cell, where the glucose is converted by the plant into a kind of biological battery called starch which it stores for later use, such as winter when photosynthesis is turned off. Other uses of glucose by the plant include respiration, creating the sweetness in fruit, conversion into cellulose for cell-wall strengthening, forming fatty lipids for storage in seeds, and generating proteins, which are an important source of food for all living things. In this case, our carbon molecule rests quietly in its cell waiting to be summoned when the leaf is suddenly ripped from its host by a hungry herbivore. After a brief but tumultuous ride through grinding teeth, the molecule slides downward into a smelly stomach and eventually passes into the animal’s digestive tract, where the starch is processed and the carbon absorbed into a cell of muscle tissue. A month later, the cycle is completed when the animal breaks a leg and dies in the wild. As it decomposes, the carbon molecule is exposed to the air where it picks up two oxygen atoms swinging by and together they rise upward to begin the joyride all over again.

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The Emergence of Biological Carbon-Fixation

The core structure of the metabolic network is very similar across all organisms, which suggests an early origin. Centrally located within this network are the sugar phosphate reactions of glycolysis and the pentose phosphate pathway. Together with the overlapping reactions of the Entner–Doudoroff pathway and of the Calvin cycle, they provide the precursor metabolites required for the synthesis of RNA, DNA, lipids, energy and redox coenzymes and amino acids—key molecules required for life. 11

Analysis of the Intermediary Metabolism of a Reductive Chemoautotroph
All extant life forms depend, directly or indirectly, on the autotrophic fixation of the dominant elements of the biosphere: carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur. A canonical network of reactions constitute the anabolism of a reductive chemoautotroph. Separating this network into subgraphs reveals several empirical generalizations: 

(1) acetate (acetyl-CoA), pyruvate, phosphoenol pyruvate, oxaloacetate, and 2-oxoglutarate serve as universal starting points for all pathways leading to the universal building blocks—20 amino acids and 4 ribonucleotide triphosphates; 
(2) all pathways are anabolic; 
(3) all reactions operate by complete utilization of outputs with no molecules left behind as waste, ensuring conservation of information; 
(4) the core metabolome of 120 compounds is acidic, consisting of compounds containing phosphoric or carboxylic acid or both; and 
(5) the core network is both brittle—vulnerable to a single break—and robust. Preliminary analysis of the chemical reactions and resultant structures reveals (a) a sparseness among possible molecular structures; (b) subdomains in the network; and (c) restriction of anabolism to a small set of rudimentary organic reactions with limited diversity in chemical mechanisms. These generalizations have implications for biogenesis and trophic ecology.

The empirical generalizations applicable to the entire metabolic map are as follows: 
1. The universal atomic constituents of metabolism are carbon, hydrogen, oxygen, nitrogen, phosphorus, and sulfur. 
2. All autotrophic pathways are anabolic. 
3. When an anabolic pathway results in the splitting of a molecule, all of the resulting product molecules enter into other anabolic pathways. We have designated this phenomenon as “No molecule left behind.” This generalization involves a conservation of information as well as a conservation of inputs in autotrophic anabolism. 
4. All anabolic networks have their starting points for all of the synthetic pathways in the following five nodal molecules: 

-acetate (acetyl-CoA) 
-pyruvate 
-phosphoenolpyruvate 
-2-oxoglutarate 
-oxaloacetate 

Including the monomers or elementary repeated units, the essential core metabolism required for autotrophic life contains only about 125 distinct compounds 15  One classification that is important to the scale dependence of metabolism is that the monomers are of only three types: amino acids (20 standard acids and a few idiosyncratically used variants), nucleic acids (four RNA and four DNA of which three share the same nucleobases), and sugars (a diversified group of which most simple members have 3–6 carbon atoms). All essential macromolecules larger than cofactors are oligomers, meaning that each polymer is made from only one kind of monomer. Since autotrophic organisms are biosynthetically complete, their intermediary metabolism is also an ecologically self-sufficient metabolism. Within their intermediary metabolism, by separating the macroscopic but chemically simple and redundant oligomer sectors from the core, we may obtain a model for the organic chemistry of minimal autotrophy. We will argue that the correct understanding of the core and anabolic pathways, both in the fan and in bowties, comes from the simpler realization in minimal anabolism of the kind found in Aquifex. The core contains carbon fixation and the biosynthesis of the small number of universally essential metabolites. Anabolic pathways reflect opportunities to assemble those building blocks that the core has made available.

The Reductive Tricarboxylic Acid (rTCA) Cycle-Type CO2 Fixation
The reductive tricarboxylic acid (rTCA) cycle is among the most plausible candidates for the first autotrophic metabolism in the earliest life. 26 A drawback of the FeS-driven CO2 fixation is that the electron supply ceases when the FeS surface is fully oxidized. Organic molecules thus need to be transported onto fresh FeS via diffusion and/or convection to continue their reductions. Abiotic CO2 fixation is among the most fundamental steps for life to originate, but no geochemically feasible process that drives the reaction has been acknowledged. 

Among the regularities in core metabolism, the one that stands out above all others is the universal centralizing role of the citric acid cycle, also known as the tricarboxylic acid or TCA cycle

The citric acid cycle (CAC) – also known as the tricarboxylic acid (TCAcycle or the Krebs cycle  is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into carbon dioxide and chemical energy in the form of adenosine triphosphate (ATP). In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other biochemical reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest established components of cellular metabolism and may have originated abiogenically. 16 

The reverse tricarboxylic acid (rTCA) cycle ( reverse Krebs cycle) is a central anabolic biochemical pathway whose origins are proposed to trace back to geochemistry, long before the advent of enzymes, RNA or cells, and whose imprint remains intimately embedded in the structure of core metabolism. If it existed, a primordial version of the rTCA cycle would necessarily have been catalysed by naturally occurring minerals at the earliest stage of the transition from geochemistry to biochemistry. 4

It is a network of eleven reactions and eleven carboxylic acids, of which the smallest (acetate) has two carbons and the largest (citrate, isocitrate, cis-aconitate, and oxalosuccinate) have six.


The five “pillars of anabolism” are intermediates of the citric acid cycle, and starting points of all major pathways of anabolism (arrows). 
The precursors and their downstream products are acetate (fatty acid and isoprene alcohol lipids), pyruvate (alanine and its amino acid derivatives, sugars), oxaloacetate (aspartate and derivatives, pyrimidines), α-ketoglutarate (glutamate and derivatives, also pyrroles), and succinate (pyrroles). Molecules with homologous local chemistry are at opposite positions on the circle. Oxidation states of internal carbon atoms are indicated by color (red oxidized, blue reduced)

Outline of the reductive citric acid cycle for autotrophic CO2 fixation.
Enzyme activities: 

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.

Malate dehydrogenase (MDH) is an enzyme that reversibly catalyzes the oxidation of malate to oxaloacetate using the reduction of NAD+ to NADH. This reaction is part of many metabolic pathways, including the citric acid cycle. 18



Malate dehydrogenase (MDH)

Fumarase (or fumarate hydratase) is an enzyme that catalyzes the reversible hydration/dehydration of fumarate to malate. Fumarase comes in two forms: mitochondrial and cytosolic. The mitochondrial isoenzyme is involved in the Krebs Cycle (also known as the Tricarboxylic Acid Cycle [TCA] or the Citric Acid Cycle), and the cytosolic isoenzyme is involved in the metabolism of amino acids and fumarate. Subcellular localization is established by the presence of a signal sequence on the amino terminus in the mitochondrial form, while subcellular localization in the cytosolic form is established by the absence of the signal sequence found in the mitochondrial variety. 19



Fumarase

Fumarate reductase is the enzyme that converts fumarate to succinate, and is important in microbial metabolism as a part of anaerobic respiration 20


Fumarate reductase

Succinyl coenzyme A synthetase (SCS, also known as succinyl-CoA synthetase or succinate thiokinase or succinate-CoA ligase) is an enzyme that catalyzes the reversible reaction of succinyl-CoA to succinate.The enzyme facilitates the coupling of this reaction to the formation of a nucleoside triphosphate molecule (either GTP or ATP) from an inorganic phosphate molecule and a nucleoside diphosphate molecule (either GDP or ADP). It plays a key role as one of the catalysts involved in the citric acid cycle, a central pathway in cellular metabolism, and it is located within the mitochondrial matrix of a cell. 21


Succinyl coenzyme A synthetase

2-oxoglutarate synthase  belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with an iron-sulfur protein as acceptor. The systematic name of this enzyme class is 2-oxoglutarate:ferredoxin oxidoreductase (decarboxylating). Other names in common use include 2-ketoglutarate ferredoxin oxidoreductase2-oxoglutarate:ferredoxin oxidoreductaseKGOR2-oxoglutarate ferredoxin oxidoreductase, and 2-oxoglutarate:ferredoxin 2-oxidoreductase (CoA-succinylating). This enzyme participates in the Citric acid cycle. Some forms catalyze the reverse reaction within the Reverse Krebs cycle, as a means of carbon fixation22

 
2-oxoglutarate synthase

Isocitrate dehydrogenase (IDH)  is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate 23  Within the citric acid cycle, isocitrate, produced from the isomerization of citrate, undergoes both oxidation and decarboxylation. Using the enzyme isocitrate dehydrogenase (IDH), isocitrate is held within its active siteby surrounding arginine, tyrosine, asparagine, serine, threonine, and aspartic acid amino acids. 23



isocitrate dehydrogenase dimer

Aconitase (aconitate hydratase) is an enzyme that catalyzes the stereo-specific isomerization of citrate to isocitrate via cis-aconitate in the tricarboxylic acid cycle, a non-redox-active process 24


Aconitase

ATP citrate lyase is an enzyme that in animals represents an important step in fatty acid biosynthesis. ATP citrate lyase is important in that, by converting citrate to acetyl CoA, it links the metabolism of carbohydrates, which yields citrate as an intermediate, and the production of fatty acids, which requires acetyl CoA. In plants, ATP citrate lyase generates cytosolic acetyl-CoA precursor of thousands of specialized metabolites including waxes, sterols, and polyketides. 25

ATP citrate lyase


pyruvate synthase  is an enzyme that catalyzes the interconversion of pyruvate and acetyl-CoA. It is also called pyruvate: ferredoxin oxidoreductase  The 3 substrates of this enzyme are pyruvate, CoA, and oxidized ferredoxin, whereas its 3 products are acetyl-CoA, CO2, and reduced ferredoxin.

Four of the intermediates (pyruvate, oxaloacetate, α-ketoglutarate, and oxalosuccinate) are α-ketoacids. Three of these (excluding oxalosuccinate), plus the α-ketoacid glyoxylate are precursors to all the amino acids. The amino acids aspartate (from oxaloacetate) and glycine (from glyoxylate), in turn, are precursors to the nucleobases. Succinate is precursor to pyrroles, which chelate transition metals in essential cofactors such as cobalamin and heme. Pyruvate, via the activated form phosphoenolpyruvate (PEP), is the precursor to sugars and other carbohydrates derived from them, through the pathway known as gluconeogenesis from pyruvate to fructose. Acetate is the precursor to both fatty acids and isoprene alcohols. Because of the centrality and universality of these precursors, the TCA cycle is the central organizing topological network in any graph of not only universal metabolism, but even the aggregate union of known metabolic pathways. The TCA cycle remains topologically central, even after aggregating the known variations in core metabolism, because it is also phylogenetically central. A subset of its intermediates, and some subset of its reactions to reach them, is found in the biosynthetic pathways required by any organism (either directly or through trophic links from heterotrophs to primary producers). The complete cycle is found in organisms in either of two opposite forms: the oxidative Krebs cycle 

The five compounds acetate, pyruvate, oxaloacetate, succinate, and α-ketoglutarate are the standard universal precursors to all of biosynthesis.

This generalization appears to be universal for all autotrophs, including those that use the reductive TCA cycle, those that employ the oxidative TCA cycle, and those with the “horseshoe,” or incomplete, TCA cycle

To the question ‘Where did these sugars come from?’, we can only speculate based on the prior literature, which leaves the issue essentially open. The notion of the prebiotic Archean ocean is intriguing, particularly when considering the problem of concentration of the solutes.

Reduction of the uncertainty in the global and local conditions that facilitated prebiotic reactions remains a formidable challenge.

The Implausibility of Metabolic Cycles on the Prebiotic Earth Leslie E Orgel†
Almost all proposals of hypothetical metabolic cycles have recognized that each of the steps involved must occur rapidly enough for the cycle to be useful in the time available for its operation. It is always assumed that this condition is met, but in no case have persuasive supporting arguments been presented. Why should one believe that an ensemble of minerals that are capable of catalyzing each of the many steps of the reverse citric acid cycle was present anywhere on the primitive Earth, or that the cycle mysteriously organized itself topographically on a metal sulfide surface? The lack of a supporting background in chemistry is even more evident in proposals that metabolic cycles can evolve to “life-like” complexity. The most serious challenge to proponents of metabolic cycle theories—the problems presented by the lack of specificity of most nonenzymatic catalysts—has, in general, not been appreciated. If it has, it has been ignored. Theories of the origin of life based on metabolic cycles cannot be justified by the inadequacy of competing theories: they must stand on their own. [url= http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060018]14[/url]

Many chemists think that prebiotic CO2 fixation is unlikely since CO2 is a relatively unreactive molecule. Even when chemically reduced, it typically produces other single-carbon compounds and is not the best candidate for forming C-C bonds. Consequently, for the past 60 years much research in prebiotic chemistry has focused on how nature might have built up carbon-based molecules with other more reactive single-carbon molecules such as HCN, formaldehyde or formamide. Chemically speaking, this makes a lot of sense, but this approach is bogged down by its own problem: even if interesting chemistry is found, how can we know if it has any relevance to the origin of life, since life shows no sign of ever having done things this way? 12



13

The reverse Krebs cycle (also known as the reverse tricarboxylic acid cycle, the reverse TCA cycle, or the reverse citric acid cycle) is a sequence of chemical reactions that are used by some bacteria to produce carbon compounds from carbon dioxide and water. 10 The reaction is the citric acid cycle run in reverse: Where the Krebs cycle takes complex carbon molecules in the form of sugars and oxidizes them to CO2 and water, the reverse cycle takes CO2 and water to make carbon compounds. The reaction is a possible candidate for prebiotic early-earth conditions and, so, is of interest in the research of the origin of life. It has been found that some non-consecutive steps of the cycle can be catalyzed by minerals through photochemistry. 

The non-enzymatic version of the rTCA cycle has been hypothesized to be central to the origin of life and have unique properties. The core of intermediary metabolism in autotrophs is the citric acid cycle. In a certain group of chemoautotrophs, the reductive citric acid cycle is an engine of synthesis, taking in CO2 and synthesizing the molecules of the cycle. We have examined the chemistry of a model system of C, H, and O that starts with carbon dioxide and reductants and uses redox couples as the energy source. 9

The chart of metabolic pathways is an expression of the universality of intermediary metabolism. The reaction networks of all extant species of organisms map onto a single chart, the great unity within diversity of the living world. 
A paradox to be faced is that, at present, enzymes are required to define or generate the reaction network, and the network is required to synthesize the enzymes and their component monomers.

The core is the citric acid cycle and related reactions.

The first shell is the synthesis of amino acids, which comes from amination of core keto acids.
The second shell involves sulfur incorporation into amino acids.
The third shell requires the synthesis of dinitrogen heterocycles. We assume that metabolism recapitulates biogenesis; the number of steps from CO2 incorporation to a given biochemical index the appearance of that molecule in biogenesis.

At the core of the metabolic chart is the citric acid cycle, which is the pathway to efficient oxidation in aerobic heterotrophs. In autotrophs, the citric acid cycle is the central pathway to all biosynthesis. Lipids come from acetyl CoA, sugars from phosphoenol pyruvate, and amino acids from keto acids and other compounds in the cycle. Nucleic acid components are synthesized from amino acids and sugars. In autotrophs, the citric acid cycle is an engine of synthesis.

In chemoautotrophs, the citric acid cycle is the central starting point on the route to all biochemicals. Energy must be supplied from outside the citric acid cycle by reactions going from environmental redox couples to ATP, reduced NAD+, reduced NADP, and reduced FAD. Given this energy, the cycle is the central feature of the metabolic chart.

One approach to the origin of metabolism is, therefore, a prebiotic nonenzymatic reductive citric acid cycle.

The fixation of inorganic carbon into organic material (autotrophy) is a prerequisite for life. In the extant biosphere the reductive pentose phosphate (Calvin-Benson) cycle is the predominant mechanism by which many prokaryotes and all plants fix CO2 into biomass. However, the fact that five alternative autotrophic pathways exist in prokaryotes is often neglected. This bias may lead to serious misjudgments in models of the global carbon cycle, in hypotheses on the evolution of metabolism, and in interpretations of geological records. Here, I review these alternative pathways that differ fundamentally from the Calvin-Benson cycle. Revealingly, these five alternative pathways pivot on acetyl-coenzyme A, the turntable of metabolism, demanding a gluconeogenic pathway starting from acetylcoenzyme A and CO2. It appears that the formation of an activated acetic acid from inorganic carbon represents the initial step toward metabolism. Consequently, biosyntheses likely started from activated acetic acid and gluconeogenesis preceded glycolysis. 1

Regarding the essential parts, biologists allege that the biochemical unity that underlies the living world makes sense only if most of the central metabolic intermediates and pathways were already present in the common ancestor. This appears to be the blueprint of primordial metabolism: a network of a dozen common organic molecules (central precursor metabolites) from which all building blocks derive and which are transformed and interconnected by only a few reactions. In the extant biosphere the Calvin-Benson cycle is the predominant mechanism by which many prokaryotes and all plants fix CO2 into biomass using the key enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). Yet, this cycle is not the only option.

Apart from connecting biosynthesis to energy metabolism, a structural framework (notably forming and energizing a membrane) and a primitive hereditary mechanism must be implemented concurrently to form a functional and viable unity.

That is just another phrasing for irreducible complexity.

Acetogenic Bacteria

Wood–Ljungdahl pathway
The Wood–Ljungdahl pathway is a set of biochemical reactions used by some bacteria and archaea called acetogens. It is also known as the reductive acetyl-coenzyme A (Acetyl-CoA) pathway.[1] This pathway enables these organisms to use hydrogen as an electron donor, and carbon dioxide as an electron acceptor and as a building block for biosynthesis. 

Autotrophic theories for the origin of life propose that CO2 was the carbon source for primordial biosynthesis. Among the six known CO2 fixation pathways in nature, the acetyl-CoA (AcCoA; or Wood–Ljungdahl) pathway is the most ancient, and relies on transition metals for catalysis. 3

Modern microbes that use the AcCoA pathway typically fix CO2 with electrons from hydrogen H2, which requires complex flavin-based electron bifurcation 3. This presents a paradox: how could primitive metabolic systems have fixed CO2 before the origin of proteins? 4

Native transition metals (Fe0, Ni0 and Co0) selectively reduce CO2 to acetate and pyruvate—the intermediates and end-products of the AcCoA pathway—in near millimolar ( a  thousandth of a mole ) concentrations in water over hours to days using 1–40 bar CO2 and at temperatures from 30 to 100 °C. Geochemical CO2 fixation from native metals could have supplied critical C2 and C3 metabolites before the emergence of enzymes.

While consensus remains elusive on which pathway (if any) represents the ancestral form of carbon fixation, it has become increasingly accepted over the last 30 years that the first forms of life were likely chemoautotrophic, deriving all biomass components from CO2, and all energy from inorganic redox couples in the environment. (Photoautotrophs, in contrast, derive energy from sunlight, while heterotrophs derive energy and biomass from organic sources of carbon.) Most discussions of autotrophy in the origin of life are complicated because they combine chemical requirements for carbon and energy uptake with considerations of whether organisms or syntrophic ecosystems a were required to complete the required pathways, and the ways the resulting population processes would have related to genomics on one hand and to metabolic regulations on the other. 

If we suppose that modern life has preserved part of the inventory of primordial organic molecules – for whatever reasons of either their chemistry or commitments to higher-level molecular assemblies – then the major chemical distinction between autotrophic and heterotrophic paradigms concerns whether their mechanisms of synthesis were conserved or replaced, and whether the original molecular inventory was similar to the universal core today. By “mechanism” here we refer to the substrate-level architecture of the pathway and the elementary bond transitions; the extreme efficacy and selectivity of biological catalysts is a separate problem of the emergence of higher-order structures, which either paradigm must address. 6

The problems for deciding between autotrophic and heterotrophic origins, therefore, come from uncertainty about mechanisms of organization. Which abiotic molecules and mechanisms could ever have become incorporated into networks capable of producing high molecular complexity and of permanently colonizing the geosphere?  Did such incorporation depend on information encoded in higher-order structures such as oligomers, or was it more plausibly driven by chemical kinetics without hierarchical organization or explicitly informatic molecules? The problem of the emergence, selection, and persistence of a biosynthetic network is not easily separated from questions about higher-order organization.The rate enhancement and selectivity of oligomer RNA and polypeptide catalysts are so powerful that – if their emergence from an unsupervised chemical medium were not so hard to explain – they might seem to provide a plausible route to replace practically any abiotic synthetic mechanism or to innovate any new pathway. The organization of such a “top-down” controlled metabolism would most naturally be explained by a process of Darwinian selection.

Here we argue that a key quantitative feature of metabolism to be explained is the number of universal small core metabolites. It is 287 – a number much larger than the number of comparably complex molecules appearing with non-vanishing probability in a Gibbs equilibrium ensemble, but much smaller than the 10^7 molecules of comparable complexity indexed by PubChem.

Chemoautotrophs that fix carbon by the reductive tricarboxylic acid cycle represents one of the dominant bacterial life forms that make a major contribution to biomass production. From the viewpoint of biogenesis, construction of a canonical chart of intermediary metabolism for this class of organisms may help us to understand early cellular evolution and point us to the last universal common ancestor. Data-mining the KEGG Pathways database enabled us to integrate required biosynthetic pathways and derive a chart that represents the complete anabolic network of a reductive chemoautotroph. Compounds of this metabolic network together constitute a representative minimal metabolome that comprises 287 metabolites. These compounds have been classified into different groups including those compounds that form nodes in the network. It can be seen that a relatively sparse set of organic chemical reactions dominate the anabolic synthesis in the assembly of the minimal autotrophic metabolome. Empirical generalizations that result from analyzing this metabolic network may aid in elucidating selection rules that govern its emergence and further evolution and may also help in delineating attributes that impart the observed robustness to these metabolites. 7  There were no selective forces yet.  

In the course of studying biogenesis, we became aware of bacteria that were reductive autotrophs and fixed carbon from carbon dioxide through the reductive tricarboxylic acid (rTCA) cycle. Since these organisms synthesized all organics from carbon dioxide, hydrogen, ammonia, and hydrogen sulfide, it seemed apparent that a chart of the metabolic pathways of these organisms would make an interesting comparison to oxidative heterotrophs and might point to the last universal common ancestor.

Autotrophic carbon fixation and extremophily are recognized to be two likely hallmarks of primordial organisms. Thus, the most favoured candidates for investigating the origins and earliest evolution of life are the extremophiles, and in particular the hyperthermophilic organisms. 

We selected Aquifex aeolicus as the central candidate for developing a complete chart of anabolic intermediary metabolism. Such a chart constitutes a representative minimal metabolome—a collection of all the small molecules expressed by an organism over time— of reductive chemoautotrophic bacteria. Our choice of Aquifex is further justified by its placement at the deepest phylogenetic branch point, closest to the last universal common ancestor. A. aeolicus has one of the smallest genomes among free-living bacteria and the smallest among free-living autotrophic bacteria, indicating limited, if not minimal, metabolic flexibility.



Results and Discussion
Chemolithoautotrophs are organisms that acquire energy by redox reactions of inorganic compounds and utilize CO2 as the sole source of carbon for anabolic synthesis of compounds of intermediary metabolism for growth. At the present time, at least five autotrophic mechanisms have been well established for carbon assimilation; among these, the reductive TCA cycle (rTCA) is the pathway utilized by many reductive chemoautotrophs. Recently, in Aquificales, which is a strictly thermophilic bacterial lineage of chemoautotrophs discovered at hydrothermal vents worldwide, the rTCA-based mechanism of carbon fixation has been identified in all three families of the phylum. This lineage that is placed phylogenetically near the root includes Aquifex aeolicus, Thiomicrospira denitrificans, and Hydrogenobacter thermophilus, the main reference organisms that contributed to the construction of the complete anabolic chart of metabolism. Figure above depicts the reductive TCA cycle, which may be considered the core of intermediary metabolism. The rTCA cycle is network-autocatalytic and can self-amplify, promoting growth. A supply of one equivalent of any of the main components of this cycle yields two equivalents of the same component at the end of the cycle.

The biochemistry of intermediary metabolism constitutes a relatively sparse set of chemical reactions. All these reactions are catalyzed by enzymes. Four of the 12 steps are the relatively simple addition or removal of water, while the other 8 are mediated by specific cofactorsSo not only the origin of enzymes in the rTCA cycle have to be explained, but as well these co-factors. Cofactors are a special class of molecules that we term chimeromers, which function as construction enablers in synthesizing the components of the metabolome.

The rTCA cycle shown in Figure above is the core of synthesis in autotrophic organisms and supplies source compounds for the building blocks that undergo condensation and polymerization reactions to yield macromolecules. This autocatalytic cycle has five major source nodes (i) pyruvate, (ii) phosphoenolpyruvate, (iii) acetyl-CoA, (iv) 2-oxoglutarate, and (v) oxaloacetate. All anabolic pathways have their origins in these five source nodes for the synthesis of the entire metabolome.

The components of a chemoautotrophic metabolome can be grouped as follows. The nodal molecules of the rTCA cycle are the starting compounds and go through a progressive process via specific biosynthetic pathways in which they are modified stepwise as chemical intermediates in a limited set of chemical reactions (see Fig. 1 and Supplemental Fig. 1)— eventually yielding monomers, which are small molecules . Most of the monomers serve as building blocks that undergo iterative dehydration reactions to generate mid-sized as well as long-chain polymers  that are proteins, DNA, RNA, carbohydrates, isoprenoids, and peptidoglycan (which makes up the cell wall), most basic building-block monomers, for example Leu (leucine) and dATP (2′-deoxyadenosine 5′-triphosphate), belong to the class of “Precursors to Polymerization” (PP); these compounds do not undergo any further chemical transformation other than polymerization. Other monomers, such as aspartic acid and guanosine triphosphate (GTP), are termed “Nodal Precursors to Polymerization” (NPP), and as the name implies, these compounds are utilized in more than one reaction in addition to polymerization. That is, they may be further modified and integrated, totally or partially, with other compounds—for example, in condensation reactions. The rest of the metabolome components are pathway intermediates (I) such as 2-isopropyl malate and orotate, most of which do not undergo more than one chemical transformation; the subset of compounds that are nodal in this class of intermediates are termed “Nodal Intermediates “(NI), for example, phosphoenolpyruvate and 5-phosphoribosyl-1-pyrophosphate (PRPP). These compounds are generated in one chemical reaction and processed and modified in more than one reaction. The lipid constituents of the cell membrane are divided into “Lipid Intermediates” (LI) and “Lipid Components” (LC), which are the terminal lipid monomers.

A small subset of monomers, conventionally known as cofactors, are a part of and essential to the making of all metabolomes. These are terminal monomers and belong to a distinct class of compounds that we propose to call chimeromers. In any given metabolome, most of the cofactors are heterocyclic compounds, and in particular, in the autotrophic metabolome under discussion, all of them are heterocyclic nitrogenous compounds. Unlike the monomers of the three major building-block categories that are synthesized by compound progression of rTCA cycle nodal molecules, the cofactors are synthesized starting from monomers and intermediates. These are transformed to yield heterocyclic compounds that are analogues of the ring systems of pyridine, pyrimidine, thiazole, pterin, and isoalloxazine (Begley, 2006). These compounds appear to be a noncongruent mosaic of members of monomers—namely amino acids, nucleotides, and their pathway intermediates. Typical examples are CoA, that has an AMP handle bridged through pantothenic acid to a modified (decarboxylated) cysteine and S-adenosyl-L-methionine (SAM) which is a direct chimera of ATP and methionine. In addition to CoA and SAM, many other cofactors like NAD, NADP, FAD, and ATP are all nucleotides or contain heterocyclic nitrogenous bases as seen in thiamin diphosphate (ThPP) and tetrahydrofolate (THF). While the intermediates of chimeromer synthesis are abbreviated as I, the terminal chimeromers that are the cofactors are denoted by CF in Supplemental Table 1 (online at http://www.biolbull.org/supplemental/). We have introduced the term chimeromers because there does not seem to be an existing term that describes molecules made of mixed monomers of different classes.

More than half of the compounds are intermediates in the biosynthesis of the monomeric building blocks that polymerize to yield macromolecules.  This network portrays the canonical chart of autotrophic intermediary metabolism that composes the minimal metabolome of a reductive chemoautotroph. Among the different types of chemical reactions required, a sparse set of simple reactions that dominate and cause chemical transformations stepwise and advance the start compounds through intermediates to the final monomers are represented by arrows that are color-coded. These reactions include

(i) oxidation-reduction, 
(ii) carboxylation-decarboxylation,
(iii) hydrolysis-dehydration, 
(iv) phosphorylation-dephosphorylation, 
(v) amination, and 
(vi) acylation;

all these reactions are enabled by specific cofactors in enzyme-catalyzed transformations. While we attempt to delineate principles that may govern the selection of these compounds and the evolution of the autotrophic network, simple analysis has yielded several empirical correlations that would aid in deriving the set of selection rules. 

Syntrophysynthrophycross-feeding, or cross feeding is the phenomenon that one species lives off the products of another species.  5


b A carboxylic acid /ˌkɑːrbɒkˈsɪlɪk/ is an organic compound that contains a carboxyl group (C(=O)OH).The general formula of a carboxylic acid is R–COOH, with R referring to the rest of the (possibly quite large) molecule. Carboxylic acids occur widely and include the amino acids (which make up proteins) and acetic acid (which is part of vinegar and occurs in metabolism). 17

1. http://sci-hub.tw/https://www.annualreviews.org/doi/10.1146/annurev-micro-090110-102801
2. https://en.wikipedia.org/wiki/Wood%E2%80%93Ljungdahl_pathway
3. https://www.frontiersin.org/articles/10.3389/fmicb.2018.00401/full
4. http://sci-hub.tw/https://www.nature.com/articles/s41559-018-0542-2
5. https://en.wikipedia.org/wiki/Syntrophy
6. http://tuvalu.santafe.edu/~desmith/PDF_pubs/OQOL_Smith_auto_hetero.pdf
7. http://sci-hub.tw/https://www.journals.uchicago.edu/doi/10.1086/BBLv216n2p126
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306138/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC16608/
10. https://en.wikipedia.org/wiki/Reverse_Krebs_cycle
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023397/
12. https://natureecoevocommunity.nature.com/users/62052-joseph-moran/posts/32286-an-acetyl-coa-pathway-before-enzymes
13. http://sci-hub.tw/https://www.nature.com/articles/nrmicro2365
14. [url= http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060018] http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060018[/url]
15. THE ORIGIN AND NATURE OF LIFE ON EARTH The Emergence of the Fourth Geosphere, page 179
16. https://en.wikipedia.org/wiki/Citric_acid_cycle
17. https://en.wikipedia.org/wiki/Carboxylic_acid
18. https://en.wikipedia.org/wiki/Malate_dehydrogenase
19. https://en.wikipedia.org/wiki/Fumarase
20. https://pt.wikipedia.org/wiki/Fumarato_redutase
21. https://en.wikipedia.org/wiki/Succinyl_coenzyme_A_synthetase
22. https://en.wikipedia.org/wiki/2-oxoglutarate_synthase
23. https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase
24. https://en.wikipedia.org/wiki/Aconitase
25. https://en.wikipedia.org/wiki/ATP_citrate_lyase
26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745552/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040112/



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Abiogenesis is understood enough to conclude, that the probabilities are too small, that life could have emerged naturally, without a guiding intelligence. A 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.

" Abiotic CO2 fixation is among the most fundamental steps for life to originate, but no geochemically feasible process that drives the reaction has been acknowledged. "
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745552/

The problem is: Even IF a non-enzymatic process could fix Carbon. So what?  To have fixed Carbon available is a tiny problem faced the challenge to obtain all basic building blocks to make life. But even IF somehow early earth came up with a mechanism to fix Carbon, the next question would be the transition from non-enzymatic Carbon fixation, to the TCA Cycle.  How could abiotic processes produce these enzymes if they are encoded in DNA? It takes these enzymes to make DNA ( which requires carbon ). But it takes DNA to make these enzymes. Someone can propose self-replicating RNA's, that might have been precursors of DNA as information storage device.  But that does not solve the riddle: Where did the information come from to encode the blueprint to make these enzymes?

Estimating the probability of just a single 150-amino acid functional protein coming into existence by random chance at 10^164.  According to Borel's law, any occurrence with a chance of happening that is less than one chance out of 10^50, is an occurrence with such a slim a probability that is, in general, statistically considered to be zero. (10^50 is the number 1 with 50 zeros after it, and it is spoken: "10 to the 50th power")

And - the machinery to polymerize proteins, namely the ribosome, another ultracomplex molecular factory,  was not extant, besides the complete production line for protein synthesis, which is irreducible and interdependent:

The interdependent and irreducible structures required to make proteins
http://reasonandscience.catsboard.com/t2039-the-interdependent-and-irreducible-structures-required-to-make-proteins

From the book: Lateral gene transfer in evolution, page 6
To control and process DNA as an information and storage apparatus, an organism REQUIRES AT LEAST a minimal set of DNA polymerase, DNA ligase, DNA helicase, DNA primase, DNA topoisomarase, and a DNA-dependent RNA polymerase.

To make proteins, and direct and insert them to the right place where they are needed, at least 25 unimaginably complex biosyntheses and production-line like manufacturing steps are required. Each step requires extremely complex molecular machines composed of numerous subunits and co-factors, which require the very own processing procedure described below, which makes its origin an irreducible  catch22 problem

That is basically the reason why scientists are not finding a consensus in regards of what came first: The RNA world, or the metabolic first scenario. Truth is, they had to emerge together.  

Scientific American brought it to the point:

How Structure Arose in the Primordial Soup
About 4 billion years ago, molecules began to make copies of themselves, an event that marked the beginning of life on Earth. A few hundred million years later, primitive organisms began to split into the different branches that make up the tree of life. In between those two seminal events, some of the greatest innovations in existence emerged: the cell, the genetic code and an energy system to fuel it all. ALL THREE of these are ESSENTIAL to life as we know it, yet scientists know disappointingly little about how any of these remarkable biological innovations came about.
https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/

But there are many more parts that are life essential, what makes biological Cells irreducibly complex:

chemist Wilhelm Huck, professor at Radboud University Nijmegen
A working cell is more than the sum of its parts. "A functioning cell must be entirely correct at once, in all its complexity
http://www.ru.nl/english/@893712/protocells-formed/

More:
The Emergence of Biological Carbon-Fixation
http://reasonandscience.catsboard.com/t2419-where-did-glucose-come-from-in-a-prebiotic-world#6103

The cell is irreducibly complex
http://reasonandscience.catsboard.com/t1299-the-cell-is-irreducibly-complex

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