Prebiotic Reaction Networks in Water - a review

Prebiotic Reaction Networks in Water - a review

https://www.mdpi.com/2075-1729/10/12/352/htm

Understanding how a dynamic network of all needed synthetic pathways can come together within an enclosed volume the size of the cell remains one of the primary goals of prebiotic chemistry.

My comment: 
Biological systems are functionally organized, integrated into an interdependent network, and complex, like human-made machines and factories. The wiring or circuit board of an electrical device equals to the metabolic pathways of a biological cell. For the assembly of a biological system of multiple parts, not only the origin of the genome information to produce all proteins/enzymes with their respective subunits and assembly cofactors must be explained, but also parts availability (The right materials must be transported to the building site. Often these materials in their raw form are unusable. Other complex machines come into play to transform the raw materials into a usable form.  All this requires specific information.)  Synchronization, (these parts must be ready on hand at the building site)  manufacturing and assembly coordination (which required the information of how to assemble each single part correctly, at the right place, at the right moment, and in the right position), and interface compatibility (the parts must fit together correctly, like lock and key) . Unless the origin of all these steps is properly explained, functional complexity as existing in biological systems has not been addressed adequately.

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 12 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 12 hole course.

A number of straight-forward features have been predicted to be characteristic of plausible prebiotic chemical reaction networks.

Prebiotic network evolution: six key parameters 12th October 2015 1
Chemical evolution entailed the heritable alteration of the identities of a collection of molecular species prior to formal genotype–phenotype relationships. As such, it must have had some capacity to encode information (i.e., some reduction in ambiguity about all possible molecular ensembles), but clearly without the coding specificity available to biological systems.

My comment:

 Blueprints and assembly instructions dictate the making of complicated machines and factories and require machine engineers and builders.

Analogously, genotype and epigenetics dictate phenotype, and are equally in a causal relationship. Since biological systems are far more sophisticated and complex than anything ever devised and invented by man, evidently and logically, they also had most likely to be instantiated by an intelligent engineer and builder.

Herschel 1830 1987, p. 148:
“If the analogy of two phenomena be very close and striking, while, at the same time, the cause of one is very obvious, it becomes scarcely possible to refuse to admit the action of an analogous cause in the other, though not so obvious in itself.”

A metaphor (“A biological cell is like a production system”) demonstrates that similar behaviors are driven by similar causal mechanisms.

Michael Denton’s 1985 Evolution: A Theory in Crisis:
The inference to design is a purely a posteriori induction based on a ruthlessly consistent application of the logic of analogy.

Chemical evolutionary settings have been described as ‘‘pre-life’’ in which information can be generated through selection in the absence of formal replication.

My comment:

The simplest free-living bacteria is Pelagibacter ubique. 13 It is known to be one of the smallest and simplest, self-replicating, and free-living cells.  It has complete biosynthetic pathways for all 20 amino acids.  These organisms get by with about 1,300 genes and 1,308,759 base pairs and code for 1,354 proteins.  If a chain could link up, what is the probability that the code letters might by chance be in some order which would be a usable gene, usable somewhere—anywhere—in some potentially living thing? If we take a model size of 1,200,000 base pairs, the chance to get the sequence randomly would be 4^1,200,000 or 10^722,000. Leading scientists have calculated that the statistical probability of life emerging by random unguided events, is far beyond the limit of Borel's law, which is in the order of 1 in 10^50.

3. The Miller-Urey Experiment
Different distributions of products may result even though the initial conditions are virtually identical, a feature reminiscent of biological systems

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

Questions: 2

How could ammonia (NH3), the precursor for amino acid synthesis, have accumulated on prebiotic earth, if the lifetime of ammonia would be short because of its photochemical dissociation?
How could prebiotic events have delivered organosulfur compounds required for a few amino acids used in life, if in nature sulfur exists only in its most oxidized form (sulfate or SO4), and only some unique groups of procaryotes mediate the reduction of SO4 to its most reduced state (sulfide or H2S)?
How did unguided stochastic coincidence select the right amongst over 500 that occur naturally on earth?
How was the concomitant synthesis of undesired or irrelevant by-products avoided?
How were bifunctional monomers, that is, molecules with two functional groups, so they combine with two others selected, and unifunctional monomers (with only one functional group) sorted out?
How did prebiotic events produce the twenty amino acids used in life? Eight proteinogenic amino acids were never abiotically synthesized under prebiotic conditions.
How did a prebiotic synthesis of biological amino acids avoid the concomitant synthesis of undesired or irrelevant by-products?
How could achiral precursors of amino acids have produced and concentrated only left-handed amino acids? ( The homochirality problem )
How did the transition from prebiotic enantiomer selection to the enzymatic reaction of transamination occur that had to be extant when cellular self-replication and life began?
How would natural causes have selected twenty, and not more or less amino acids to make proteins?
How did natural events have foreknowledge that the selected amino acids are best suited to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets inside proteins?
How did nature "kHow could ammonia (NH3), the precursor for amino acid synthesis, have accumulated on prebiotic earth, if the lifetime of ammonia would be short because of its photochemical dissociation?
How could prebiotic events have delivered organosulfur compounds required in a few amino acids used in life, if in nature sulfur exists only in its most oxidized form (sulfate or SO4), and only some unique groups of procaryotes mediate the reduction of SO4 to its most reduced state (sulfide or H2S)?
How did unguided stochastic coincidence select the right amongst over 500 that occur naturally on earth?
How was the concomitant synthesis of undesired or irrelevant by-products avoided?
How were bifunctional monomers, that is, molecules with two functional groups so they combine with two others selected, and unifunctional monomers (with only one functional group) sorted out?
How did prebiotic events produce the twenty amino acids used in life? Eight proteinogenic amino acids were never abiotically synthesized under prebiotic conditions.
How did a prebiotic synthesis of biological amino acids avoid the concomitant synthesis of undesired or irrelevant by-products?
How could achiral precursors of amino acids have produced and concentrated only left-handed amino acids? (The homochirality problem)
How did the transition from prebiotic enantiomer selection to the enzymatic reaction of transamination occur that had to be extant when cellular self-replication and life began?
How would natural causes have selected twenty, and not more or less amino acids to make proteins?
How did natural events have foreknowledge that the selected amino acids are best suited to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets inside proteins?
How did nature "know" that the set of amino acids selected appears to be near ideal and optimal?
How did Amino acid synthesis regulation emerge?  Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low.
How did the transition from prebiotic synthesis to cell synthesis of amino acids occur? A minimum of 112 enzymes is required to synthesize the 20 (+2) amino acids used in proteins.now" that the set of amino acids selected appears to be near ideal and optimal?
How did Amino acid synthesis regulation emerge?  Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low.
How did the transition from prebiotic synthesis to cell synthesis of amino acids occur? A minimum of 112 enzymes is required to synthesize the 20 (+2) amino acids used in proteins.

5. The Formose Reaction
Producing ribose under realistic conditions has proven even more problematic. Prebiotic chemists have proposed that ribose could have arisen on the early earth as the by-product of a chemical reaction called the formose reaction. The formose reaction is a multistep chemical reaction that begins as molecules of formaldehyde in water react with one another. Along the way, the formose reaction produces a host of different sugars, including ribose, as intermediate by-products in the sequence of reactions. But, as Shapiro has pointed out, the formose reaction will not produce sugars in the presence of nitrogenous substances.11 These include peptides, amino acids, and amines, a category of molecules that includes the nucleotide bases. This obviously poses a couple of difficulties. First, it creates a dilemma for scenarios that envision proteins and nucleic acids arising out of a prebiotic soup rich in amino acids. Either the prebiotic environment contained amino acids, which would have prevented sugars (and thus DNA and RNA) from forming, or the prebiotic soup contained no amino acids, making protein synthesis impossible. Of course, RNA-first advocates might try to circumvent this difficulty by proposing that proteins arose well after RNA. Yet since the RNA-world hypothesis envisions RNA molecules coming into contact with amino acids early on within the first protocellular membranes (see above), choreographing the origin of RNA and amino acids to ensure that the two events occur separately becomes a considerable problem.3

6. Reaction Networks for Ribonucleotide Synthesis

The implausibility of prevital RNA and DNA  synthesis  5

RNA & DNA: It's prebiotic synthesis: Impossible !! Part 1
https://www.youtube.com/watch?v=-ZFlmL_BsXE

RNA & DNA: It's prebiotic synthesis: Impossible !! Part 2
https://www.youtube.com/watch?v=dv4mUjmuRRU

Questions:  3

How would prebiotic processes have purified the starting molecules to make RNA and DNA which were grossly impure? They would have been present in complex mixtures that contained a great variety of reactive molecules.
How did the Synthesis of the nitrogenic nucleobases in prebiotic environments occur?
How did fortuitous accidents select the five just-right nucleobases to make DNA and RNA, Two purines, and three pyrimidines?
How did unguided random events select purines with two rings, with nine atoms, forming the two rings: 5 carbon atoms and 4 nitrogen atoms, amongst almost unlimited possible configurations?
How did stochastic coincidence select pyrimidines with one ring, with six atoms, forming its ring: 4 carbon atoms and 2 nitrogen atoms, amongst an unfathomable number of possible configurations?
How did random trial and error foresee that this specific atomic arrangement of the nucleobases is required to get the right strength of the hydrogen bond to join the two DNA strands and form Watson–Crick base-pairing?
How did mechanisms without external direction foresee that this specific atomic arrangement would convey one of, if not the best possible genetic system to store information?
How would these functional bases have been separated from the confusing jumble of similar molecules that would also have been made?
How were high-energy precursors to produce purines and pyrimidines produced in a sufficiently concentrated form and joined to the assembly site?
How could the adenine-uracil interaction function in any specific recognition scheme under the chaotic conditions of a "prebiotic soup" considering that its interaction is weak and nonspecific?
How could sufficient uracil nucleobases accumulate in prebiotic environments in sufficient quantities, if it has a half-life of only 12 years at 100◦C ?
How could the ribose 5 carbon sugar rings which form the RNA and DNA backbone have been selected, if 6 or 4 carbon rings, or even more or less, are equally possible but non-functional?
How would the functional ribose molecules have been separated from the non-functional sugars?
How were the correct nitrogen atom of the base and the correct carbon atom of the sugar selected to be joined together?
How could right-handed configurations of RNA and DNA have been selected in a racemic pool of right and left-handed molecules? Ribose must have been in its D form to adopt functional structures ( The homochirality problem )
How could random events have brought all the 3 parts together and bonded them in the right position ( probably over one million nucleotides would have been required ?)
How could prebiotic reactions have produced functional nucleosides? (There are no known ways of bringing about this thermodynamically uphill reaction in aqueous solution)
How could prebiotic glycosidic bond formation between nucleosides and the base have occurred if they are thermodynamically unstable in water, and overall intrinsically unstable?
How could  RNA nucleotides have accumulated, if they degrade at warm temperatures in time periods ranging from nineteen days to twelve years? These are extremely short survival rates for the four RNA nucleotide building blocks.
How was phosphate, the third element, concentrated at reasonable concentrations?. (The concentrations in the oceans or lakes would have been very low)
How would prebiotic mechanisms phosphorylate the nucleosides at the correct site (the 5' position) if, in laboratory experiments, the 2' and 3' positions were also phosphorylated?
How could phosphate have been activated somehow? In order to promote the energy dispendious nucleotide polymerization reaction, and (energetically uphill) phosphorylation of the nucleoside had to be possible.
How was the energy supply accomplished to make RNA? In modern cells, energy is consumed to make RNA.
How could a transition from prebiotic to biochemical synthesis have occurred? There are a huge gap and enormous transition that would be still ahead to arrive at a fully functional interlocked and interdependent metabolic network.
How could  RNA have formed, if it requires water to make them, but RNA cannot emerge in water and cannot replicate with sufficient fidelity in water without sophisticated repair mechanisms in place?
How would the prebiotic synthesis transition of RNA to the highly regulated cellular metabolic synthesis have occurred?  The pyrimidine synthesis pathway requires six regulated steps, seven enzymes, and energy in the form of ATP.
The starting material for purine biosynthesis is Ribose 5-phosphate, a product of the highly complex pentose phosphate pathway, which uses 12 enzymes. De novo purine synthesis pathway requires ten regulated steps, eleven enzymes, and energy in the form of ATP.

DNA is more stable than RNA. uracil (U) is replaced in DNA by thymine (T)
At the C2' position of ribose, an oxygen atom is removed by hypercomplex RNR molecular machines. The thymine-uracil exchange is the major chemical difference between DNA and RNA. Before being incorporated into the chromosomes, this essential modification takes place. The synthesis of thymine requires seven enzymes. De novo biosynthesis of thymine is an intricate and energetically expensive process.
All in all, not considering the metabolic pathways and enzymes required to make the precursors to start RNA and DNA synthesis, at least 26  enzymes are required. How did these enzymes emerge, if DNA is required to make them? 

7. Nonenzymatic Analogues and Models of Metabolic Cycles
Metabolism-first approaches to the origins-of-life problem offer an alternative, if not complementary, avenue of investigation. Rather than being a later product of Darwinian evolution, these approaches assume that the universal core of metabolism is closely linked to the abiotic geochemistry from which primitive versions of these networks originally arose. Once this core protometabolic network was established, genetic replicators like RNA emerged later. Hence, metabolism-first scenarios place a greater emphasis

My comment: 6

There is no evidence that the atoms required to make the basic building blocks of life were extant in a usable form on the early earth. A paper published by Nature magazine in 2016 claimed, that the foremost and only known nitrogen-fixing mechanism trough nitrogenase enzymes was extant in the last universal common ancestor. 1 But nitrogenase enzymes are of the HIGHEST complexity, truly marvels of nanomachinery, a molecular sledgehammer. 

The two main constituents of our atmosphere, oxygen (21%) and nitrogen (78%), both play important roles in the makeup of living things. Both are integral parts of the amino acids that join together in long chains to make all proteins, and of the nucleotides which do the same thing to form DNA and RNA. Getting elemental oxygen (O2) to split apart into atoms and take part in the reactions and structures of life is not hard; in fact, oxygen is so reactive that keeping it from getting into where it's not wanted becomes the more challenging job. However, elemental nitrogen poses the opposite problem. Like oxygen, it is diatomic (each molecule contains two N atoms) in its pure form (N2); but, unlike oxygen, each of its atoms is triple-bonded to the other. This is one of the hardest chemical bonds of all to break. So, how can nitrogen be brought out of its tremendous reserves in the atmosphere and into a state where it can be used by living things?

It is claimed that mineral-catalyzed dinitrogen reduction might have provided a significant source of ammonia to the Hadean ocean. But, there is a huge gap to go from such scenario to the ammonia production through nitrogenase enzymes. 

The chief enzyme is nitrogenase. With assistance from an energy source (ATP) and a powerful and specific complementary reducing agent (ferredoxin), nitrogen molecules are bound and cleaved with surgical precision. In this way, a ‘molecular sledgehammer’ is applied to the NN bond, and a single nitrogen molecule yields two molecules of ammonia. The ammonia then ascends the ‘food chain’, and is used as amino groups in protein synthesis for plants and animals. This is a very tiny mechanism but multiplied on a large scale it is of critical importance in allowing plant growth and food production on our planet to continue. 1

One author summed up the situation well by remarking, ‘Nature is really good at it (nitrogen-splitting), so good in fact that we've had difficulty in copying chemically the essence of what bacteria do so well.’ If one merely substitutes the name of God for the word 'nature', the real picture emerges.


The second problem is how to fix carbon dioxide to make glucose. 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 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. 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 the first organism.  

The hypothesis is 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.

But even, if, let's suppose, somehow, carbon fixation would have started on metal sulfide surface, there is an unbridgeable gap from that kind of prebiotic self-organization and carbon production, to even the most simple enzymatic carbon fixation pathway, used in anaerobic bacteria. the reductive tricarboxylic acid cycle rTCA is claimed to be the best candidate. That cycle requires nine sophisticated enzymes, some with complex molybdenum co-factors, which also have to be synthesized in highly ordered sequential multistep production pathways by various enzymes. How did that come to be without evolution? 3

Outlining just two elements demonstrates the size of the problem. But overall metabolism is based on seven non-metal elements, H, C, N, 0, P, S, and Se. With these elements, all the major polymers of all cells are made. Hence the major metabolic pathways involve them. In total, over 20 different elements, including heavy elements, like molybdenum, are absolutely essential for life to start.

The emergence of concentrated suites of just the right mix thus remains a central puzzle in origin-of-life research. Life requires the assembly of just the right combination of small molecules into much larger collections - "macromolecules" with specific functions. Making macromolecules is complicated by the fact that for every potentially useful small molecule in the prebiotic soup, dozens of other molecular species had no obvious role in biology. Life is remarkably selective in its building blocks, whereas the vast majority of carbon-based molecules synthesized in prebiotic processes have no obvious biological use. 5

8. Conclusions
Recent research efforts have demonstrated progress in prebiotic reaction networks across multiple fronts, including analytical, theoretical and experimental strategies.

Reply:
Paradoxes in the origin of life. 2015 Jan 22 Benner SA1.:
We are now 60 years into the modern era of prebiotic chemistry. That era has produced tens of thousands of papers attempting to define processes by which “molecules that look like biology” might arise from “molecules that do not look like biology” …. For the most part, these papers report “success” in the sense that those papers define the term…. And yet, the problem remains unsolved

The Factory maker argument 7 8
1. Living Cells store very complex genetic and epigenetic information through the genetic code, and over twenty epigenetic languages, translation systems, and signaling networks. These information systems instruct the making and operation of cells and multicellular organisms. The operation of cells is close to thermodynamic perfection, and its operation occurs analogously to computers. Cells ARE computers in a literal sense, using boolean logic. Each cell hosts millions of interconnected molecular machines, production lines and factories analogous to factories made by man. They are of unparalleled gigantic complexity, able to process constantly a stream of data from the outside world through signaling networks. Cells operate robot-like,  autonomously. They adapt the production and recycle molecules on demand. The process of self-replication is the epitome of manufacturing advance and sophistication.
2. The origin of blueprints containing the instructional complex information, and the fabrication of complex machines and interlinked factories based on these instructions, which produce goods for specific purposes, are both always the result of intelligent setup.
3. Herschel 1830 1987, p. 148: “If the analogy of two phenomena be very close and striking, while, at the same time, the cause of one is very obvious, it becomes scarcely possible to refuse to admit the action of an analogous cause in the other, though not so obvious in itself.” A metaphor (“A biological cell is like a production system”) demonstrates that similar behaviors are driven by similar causal mechanisms. 
4. Therefore, the origin of biological information and self-replicating cell factories is best explained by the action of a brilliant super powerful intelligent designer, who created life for his own purposes.

Devolution indicates the impossibility of random assembly to get complex macromolecules to kick-start life
1. At least 1300 proteins are required as building blocks for the simplest living cell to come to existence
2. Proteins are highly complex structures. The probability of random creation of complex proteins, the assemblage of the needed 1300 in one place in nature without any control is less than 10^722.000 or impossible.
3. According to the science paper: Paradoxes of life, Steve Benner reports: Systems, given energy and left to themselves, DEVOLVE to give uselessly complex mixtures, “asphalts”.  The literature reports (to our knowledge) exactly  ZERO CONFIRMED OBSERVATIONS where “replication involving replicable imperfections” (RIRI) evolution emerged spontaneously from a devolving chemical system. it is IMPOSSIBLE for any non-living chemical system to escape devolution to enter into the Darwinian world of the “living”. 
4. Such impossibility of random events indicates the necessity of an intelligent designer.


1. https://pubs.rsc.org/en/content/articlelanding/2015/mb/c5mb00593k/unauth#!divAbstract
2. https://reasonandscience.catsboard.com/t1279p75-abiogenesis-is-mathematically-impossible#7759
3. https://reasonandscience.catsboard.com/t2024-the-rna-world-and-the-origins-of-life
4. https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible#6870
5. https://reasonandscience.catsboard.com/t2865-rna-dna-it-s-prebiotic-synthesis-impossible
6. https://reasonandscience.catsboard.com/t2986-carbon-metabolism-is-the-most-basic-aspect-of-life#7830
7. https://reasonandscience.catsboard.com/t2895-syllogistic-arguments-of-gods-existence-based-on-positive-evidence#8182
8. https://reasonandscience.catsboard.com/t2245-abiogenesis-the-factory-maker-argument