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Origin of the canonical twenty  amino acids required for life

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Origin of the canonical twenty  amino acids required for life 

http://reasonandscience.catsboard.com/t1740-origin-of-the-canonical-twenty-amino-acids-required-for-life

The 22 amino acids required for life
Glycine
Alanine
Valine
Leucine and Isoleucine
Methionine
Proline
Phenylalanine
Tryptophan
Serine
Threonine
Aspargine
Glutamine
Tyrosine
Cysteine
Lysine
Arginine
Histidine
Aspartate ( Aspartic Acid )
Glutamate ( Glutamic Acid)




Amino acid synthesis requires solutions to four key biochemical problems

http://reasonandscience.catsboard.com/t1740-origin-of-the-canonical-twenty-amino-acids-required-for-life

1. Nitrogen fixation
Nitrogen is an essential component of amino acids. Earth has an abundant supply of nitrogen, but it is primarily in the form of atmospheric nitrogen gas (N2), a remarkably inert molecule. Thus, a fundamental problem for biological systems is to obtain nitrogen in a more usable form. This problem is solved by certain microorganisms capable of reducing the inert N = N triple-bond molecule of nitrogen gas to two molecules of ammonia in one of the most amazing reactions in biochemistry. Nitrogen in the form of ammonia is the source of nitrogen for all the amino acids. The carbon backbones come from the glycolytic pathway, the pentose phosphate pathway, or the citric acid cycle.

2. Selection of the 20 canonical bioactive amino acids
Why are 20 amino acids used to make proteins ( in some rare cases, 22) ?  Why not more or less ? And why especially the ones that are used amongst hundreds available? In a progression of the first papers published in 2006, which gave a rather shy or vague explanation, in 2017, the new findings are nothing short than astounding.  In January 2017, the paper : Frozen, but no accident – why the 20 standard amino acids were selected, reported:

" Amino acids were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets. Factors to take into account when assessing why a particular amino acid might be used include its component atoms, functional groups, biosynthetic cost, use in a protein core or on the surface, solubility and stability. Applying these criteria to the 20 standard amino acids, and considering some other simple alternatives that are not used, we find that there are excellent reasons for the selection of every amino acid. Rather than being a frozen accident, the set of amino acids selected appears to be near ideal. Why the particular 20 amino acids were selected to be encoded by the Genetic Code remains a puzzle." 

3. Homochirality
In amino acid production, we encounter an important problem in biosynthesis—namely, stereochemical control. Because all amino acids except glycine are chiral, biosynthetic pathways must generate the correct isomer with high fidelity. In each of the 19 pathways for the generation of chiral amino acids, the stereochemistry at the a -carbon atom is established by a transamination reaction that includes pyridoxal phosphate (PLP) by transaminase enzymes, which however were not extant on a prebiotic earth, which creates an unpenetrable origin of life problem. One of the greatest challenges of modern science is to understand the origin of the homochirality of life: why are most essential biological building blocks present in only one handedness, such as L-amino acids and D-sugars ?

4. Amino acid synthesis regulation
Biosynthetic pathways are often highly regulated such that building blocks are synthesized only when supplies are low. Very often, a high concentration of the final product of a pathway inhibits the activity of allosteric enzymes ( enzymes that use cofactors ) that function early in the pathway to control the committed step. These enzymes are similar in functional properties to aspartate transcarbamoylase and its regulators. Feedback and allosteric mechanisms ensure that all 20 amino acids are maintained in sufficient amounts for protein synthesis and other processes.

Of course, our God is a master Chemist, and solved these issues with ease. No problem for HIM !!

Science is absolutely clueless about how the universal genetic code emerged. And so, the optimal set of amino acids to make proteins

Francis Crick attributed it to the famous " frozen accident". Frozen accident hypothesis assumes that the formation of the genetic code is an example of a frozen accident (Crick 1968) According to this hypothesis, the genetic code was formed through a random, highly improbable combination of its components formed by an abiotic route.
Besides the problem to explain the origin of the genetic code, about which Eugene Koonin wrote: " we cannot think of a more fundamental problem in biology ", there is another enigma :
.Why are 20 amino acids used to make proteins? Why not more or less ? And why especially the ones that are used amongst hundreds available?
In a progression of the first papers published in 2011, which gave a rather shy explanation, this year, in 2017, with the progression of scientific inquiry, the new findings are nothing short than astonishing and awesome.

In following paper:

Frozen, but no accident – why the 20 standard amino acids were selected
13 January 2017
the author writes :
Amino acids were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets. Factors to take into account when assessing why a particular amino acid might be used include its component atoms, functional groups, biosynthetic cost, use in a protein core or on the surface, solubility and stability. Applying these criteria to the 20 standard amino acids, and considering some other simple alternatives that are not used, we find that there are excellent reasons for the selection of every amino acid. Rather than being a frozen accident, the set of amino acids selected appears to be near ideal.

Then, no wonder, the author continues :
Why the particular 20 amino acids were selected to be encoded by the Genetic Code remains a puzzle.
It remains a puzzle as so many other things in biology which find no answer by the ones that build their inferences on a constraint set of possible explanations, where an intelligent causal agency is excluded a priori. Selection is an active process, that requires intelligence. Attributes, that chance alone lacks, but an intelligent creator can employ to create life. The authors also write about natural selection and evolution, a mechanism that has no place to explain the origin of life.

The author: Here, I argue that there are excellent reasons for using (or not using) each possible amino acid and that the set used is near optimal.

Biosynthetic cost
Protein synthesis takes a major share of the energy resources of a cell [12]. Table 1 shows the cost of biosynthesis of each amino acid, measured in terms of number of glucose and ATP molecules required. These data are often nonintuitive. For example, Leu costs only 1 ATP, but its isomer Ile costs 11. Why would life ever, therefore, use Ile instead of Leu, if they have the same properties? Larger is not necessarily more expensive; Asn and Asp cost more in ATP than their larger alternatives Gln and Glu, and large Tyr cost only two ATP, compared to 15 for small Cys. The high cost of sulfur-containing amino acids is notable.

This is indeed completely counterintuitive and does not conform with naturalistic predictions.

Burial and surface
Proteins have close-packed cores with the same density as organic solids and side chains fixed into a single conformation [13]. A solid core is essential to stabilize proteins and to form a rigid structure with well-defined binding sites. Nonpolar side chains have therefore been selected to stabilize close-packed hydrophobic cores. Conversely, proteins are dissolved in water, so other side chains are used on a protein surface to keep them soluble in an aqueous environment.

The problem here is that molecules and an arrangement of correctly selected variety of amino acids would bear no function until life began. Functional subunits of proteins, or even fully operating proteins by their own would only have function, after life began, and the cells intrinsic operations were on the go. It is as if molecules had the inherent drive to contribute to life to have the first go, which of course is absurd. The only rational alternative is that a powerful creator had foresight, and new which arrangement and selection of amino acids would fit and work to make life possible.

Which amino acids came first?
It is plausible that the first proteins used a subset of the 20 and a simplified Genetic Code, with the first amino acids acquired from the environment.

Why is plausible? It is not only not plausible, but plain and clearly impossible. The genetic code could not emerge gradually, and there is no known explanation how it emerged. The author also ignores that the whole process of protein synthesis requires all parts of the process fully operational right from the beginning. A gradual development by evolutionary selective forces is impossible.

Energetics of protein folding
Folded proteins are stabilized by hydrogen bonding, removal of nonpolar groups from water (hydrophobic effect), van der Waals forces, salt bridges and disulfide bonds. Folding is opposed by loss of conformational entropy, where rotation around bonds is restricted, and introduction of strain. These forces are well balanced so that the overall free energy changes for all the steps in protein folding are close to zero.

Foresight and superior knowledge would be required to know how to get a protein fold that bears function, and where the forces are outbalanced naturally to get an overall energy homeostatic state close to zero.

Conclusion
There are excellent reasons for the choice of every one of the 20 amino acids and the nonuse of other apparently simple alternatives. If all else fails, one can resort to chance or a ‘frozen accident’, as an explanation.

Or to design ?!





Biosynthesis of Amino Acids
All amino acids are derived from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway. Nitrogen enters these pathways by way of glutamate and glutamine. Some pathways are simple, others are not. Ten of the amino acids are just one or several steps removed from the common metabolite from which they are derived. The biosynthetic pathways for others, such as the aromatic amino acids, are more complex. Organisms vary greatly in their ability to synthesize the 20 common amino acids. Whereas most bacteria and plants can synthesize all 20, mammals can synthesize only about half of them—generally those with simple pathways. These are the nonessential amino acids, not needed in the diet. The remainder, the essential amino acids, must be obtained from food. Unless otherwise indicated, the pathways for the 20 common amino acids presented below are those operative in bacteria. A useful way to organize these biosynthetic pathways is to group them into six families corresponding to their metabolic precursors.

Amino acids have a simple core structure consisting of an amino group, a carboxyl group, and a variable R group attached to a carbon atom. There are 20 different kinds of amino acids, each with a unique R group. The simplest and most ancient amino acid is glycine, with an R group that consists only of hydrogen. The chemistry of the various amino acids varies considerably: Some carry a positive electric charge, while others are negatively charged or electrically neutral; some are water soluble (hydrophilic), while others are hydrophobic. 8

Amino acids were among the first biological compounds found in prebiotic organic synthesis experiments (Miller 1953), and since then, a variety of mechanisms have been found by which they can be produced abiotically. 9 Depending on the starting conditions, ~12 of the 20 coded biological amino acids now have convincing prebiotic syntheses (Miller 1998). Other pathways also yield amino acids, for example, the hydrolysis of the polymer derived from the condensation of aqueous HCN gives rise to a variety of amino acids including serine, aspartic and glutamic acids, and α- and β-alanine (Ferris et al. 1978). The hydrolysis of various high-molecular-weight organic polymers (tholins) has also been found to liberate amino acids directly (Khare et al. 1986), suggesting that solution-phase conditions may be less important than previously thought if sufficiently reducing atmospheric conditions are available. There is strong evidence for some of the aromatic amino acids (phenylalanine and tyrosine) in carbonaceous chondrites (Pizzarello and Holmes 2009); however, several biological amino acids such as histidine, tryptophan, arginine, and lysine remain difficult targets of prebiotic synthesis (Miller 1998).

It is unknown when proteins or simple peptides became integral parts of biochemistry; however, heating concentrated aqueous amino acid solutions or heating amino acids in the dry state can give rise to peptides of various molecular weights depending on the conditions of synthesis. In addition to the biological amino acids, abiotic synthesis may give rise to a variety of nonbiological amino acids, including N-substituted and β- and α,α-disubstituted amino acids, among other types, some of which are found in contemporary organisms. It seems likely that abiotic synthesis provided some, but not all, of the coded amino acids in addition to many not found in coded proteins. Life’s use of the canonical 20 coded amino acids is thus likely the result of a protracted period of biological evolution. That this occurred in the context of biological systems is also likely because of the difficulty of stringing amino acids together abiotically to form long polypeptide chains. Once sufficiently robust oligomerization mechanisms were available, life would have been free to explore the combinatorial catalytic peptide space this innovation allowed access to.

There was no life yet, and even if, why would life have had the goal to explore catalytic peptide space ?? 

Nature boasts dozens upon dozens of different kinds; more than 70 different amino acids have been extracted from the Murchison meteorite alone. What’s more, most amino acids come in mirror image leftand right-handed forms, but for some reason, life uses only about 20 of these varied species, and it employs the lefthanded kinds almost exclusively. What process selected this idiosyncratic subset of molecules during the origin of life? 8



The argument of amino acids
1.  The arrangements of the amino acids in the proteins are highly specified and meaningful.
2. They are like the arrangements of letters of the alphabet into meaningful words and sentences of a book that can enrich one’s life.
3. Amino acids on their own have no ability to order themselves into any meaningful biological sequences.
4. Thus, the question is how the first protein could assemble without pre-existing genetic material.
5. The next question is how the further evolutes develop.
6. To this, there is no any answer from material scientists. The only option is – it was all designed.
7. That designer all men call God.

In his essay on the origin of life on Earth, Orgel quotes the experiments of Miller, and of Juan Oró who used the Miller model to produce adenine with hydrogen cyanide and ammonia. His conclusions overall are:

“Since then, workers have subjected many different mixtures of simple gases to various energy sources. The results of these experiments can be summarized neatly. Under sufficiently reducing conditions, amino acids form easily. Conversely, under oxidizing conditions, they do not arise at all or do so only in small amounts.” 7

How can natural processes and mechanisms write a book? compose a partiture? write a morse code, or a computer code ? how can physics write a dna code to  make the machinery to produce the machines ( enzyme proteins made of amino acids ) , many of which operate at the same time and in the same small volume of the cytosol ? By their catalytic action, these enzymes generate 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. . The system is so complex that elaborate controls are required to regulate when and how rapidly each reaction occurs. The carbon backbones come from the glycolytic pathway, the pentose phosphate pathway, or the citric acid cycle, all needing complex enzyme catalytic pathways. A living cell, even the most primitive ones, contain thousands of these enzymes, many of which operate at the same time and in the same small volume of the cytosol( the liquid inside the cell ) .  Not only do you need a encoder to produce the coded information to make the enzymes, but you need the machinery all in place right since the beginning : how could otherwise the machinery be built in a step up fashion, one enzyme after the other, if the end product is only made with all the machines in place and working in a ensemble, and the end product are actually the building blocks of these machines, that make amino acids and ATP ? that is a interdependent system. A catch22, or chicken and egg problem.  If one enzyme is not in place, the whole machinery will not work. No amino acids, no ATP ( the fuel in the cell ), no life. Without cyanobacteria - no fixed nitrogen is available. Without fixed nitrogen, no DNA, no amino-acids, no protein can be synthesised. Without DNA, no amino-acids, protein, or cyanobacteria are possible.

You can see the glycolytic pathway in the video :




read more:

http://reasonandscience.heavenforum.org/t1740-the-biosynthesis-pathway-for-the-20-standard-amino-acids#2772

Apart from the twenty universal amino acids, a more complex incorporation mechanism allows the use of a twenty-first amino acid called selenocysteine. It is found in many living organisms, including humans. In certain microorganisms, the archaea, there is even a twenty-second amino acid: pyrrolysine. 

Structural Biochemistry/Proteins/Amino Acid Biosynthesis

The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells.

http://www.ncbi.nlm.nih.gov/pubmed/25679748

nucleic acids are highly complicated polymers requiring numerous enzymes for biosynthesis. Secondly, proteins have a simple backbone with a set of 20 different amino acid side chains synthesized by a highly complicated ribosomal process in which mRNA sequences are read in triplets. Apparently, both nucleic acid and protein syntheses have extensive evolutionary histories. Supporting these processes is a complex metabolism and at the hub of metabolism are the carboxylic acid cycles.

Abiotic Synthesis of Organic Molecules

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/AbioticSynthesis.html

As for the first problem, four scenarios have been proposed.

Organic molecules
were synthesized from inorganic compounds in the atmosphere;
rained down on earth from outer space;
were synthesized at hydrothermal vents on the ocean floor;
were synthesized when comets or asteroids struck the early earth.

Assembling Polymers

Another problem is how polymers — the basis of life itself — could be assembled.

In solution, hydrolysis of a growing polymer would soon limit the size it could reach.
Abiotic synthesis produces a mixture of L and D enantiomers. Each inhibits the polymerization of the other. (So, for example, the presence of D amino acids inhibits the polymerization of L amino acids (the ones that make up proteins here on earth).

An RNA Beginning?

All metabolism depends on enzymes and, until recently, every enzyme has turned out to be a protein. But proteins are synthesized from information encoded in DNA and translated into mRNA. So here is a chicken-and-egg dilemma. The synthesis of DNA and RNA requires proteins. So proteins cannot be made without nucleic acids and nucleic acids cannot be made without proteins.

The discovery that certain RNA molecules have enzymatic activity provides a possible solution. These RNA molecules — called ribozymes — incorporate both the features required of life:storage of information
the ability to act as catalysts

From an evolutionary viewpoint, the genetic code is considered to have evolved from primitive forms containing a limited set of amino acids (1,9,10). Chemical evolution experiments suggest that only a limited number of canonical amino acids were available in prebiotic environments , and therefore the other amino acids must have been derived from the evolution of amino acid biosynthesis 3

Why These 20 Amino Acids? 4

the set of amino acids used to make proteins is the optimal set. This discovery provides new evidence that life’s chemistry stems from the work of a Creator.

Yet, hundreds of amino acids exist in nature. Biochemists want to know why the specific set of 20 amino acids, and not the others, occurs in proteins.Over the course of the last 30 years or so, biochemists have sought answers to these questions.1 At first glance, it seems conceivable that other amino acids could have been chosen to fulfill the role of some, if not all, of the canonical amino acids.

But researchers from the University of Hawaii recently offered an insightful perspective on this scientific riddle that suggests otherwise. 2 The team conducted a quantitative comparison of the range of chemical and physical properties possessed by the 20 protein-building amino acids versus random sets of amino acids that could have been selected from early Earth’s hypothetical prebiotic soup. They concluded that the set of 20 amino acids is optimal.

It turns out that the set of amino acids found in biological systems possess properties that evenly and uniformly varies across a broad range of sizes, charges, and hydrophobicities. They also demonstrate that the amino acids selected for proteins is a “highly unusual set of 20 amino acids; a maximum of 0.03% random sets out-performed the standard amino acid alphabet in two properties, while no single random set exhibited greater coverage in all three properties simultaneously.” amino acids generate amide bonds in the simplest, most efficient way possible.

Evolutionary biologists argue that the undirected processes of chemical and natural selection generated the set amino acids used to make proteins. If this is the case, some level of optimization would be expected, but not the extreme optimization just discovered by the University of Hawaii researchers. Optimization is an indicator of intelligent design, achieved through foresight and preplanning. It requires inordinate attention to detail and careful craftsmanship. By analogy, the optimized biochemistry, epitomized by the amino acid set that makes up proteins, could be rationally understood as the work of a Creator.

This amino acid set’s wide range of physicochemical properties make it possible for proteins to carry out critical chemical operations necessary for life. In my view, this insight supports the notion that life’s chemistry has been designed through the work of an intelligent Agent. 




http://en.wikipedia.org/wiki/Amino_acid_synthesis

Amino acid synthesis is the set of biochemical processes (metabolic pathways) by which the various amino acids are produced from other compounds. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesise all amino acids. For example, humans are able to synthesise only 12 of the 20 standard amino acids.

A fundamental problem for biological systems is to obtain nitrogen in an easily usable form. This problem is solved by certain microorganisms capable of reducing the inert N≡N molecule (nitrogen gas) to two molecules of ammonia in one of the most remarkable reactions in biochemistry. Ammonia is the source of nitrogen for all the amino acids. The carbon backbonescome from the glycolytic pathway, the pentose phosphate pathway, or the citric acid cycle.

As one evolutionist admitted (one of the textbook authors):

We have always underestimated cells. Undoubtedly we still do today. But at least we are no longer as naive as we were when I was a graduate student in the 1960s. Then, most of us viewed cells as containing a giant set of second-order reactions: molecules A and B were thought to diffuse freely, randomly colliding with each other to produce molecule AB—and likewise for the many other molecules that interact with each other inside a cell. This seemed reasonable because, as we had learned from studying physical chemistry, motions at the scale of molecules are incredibly rapid. … But, as it turns out, we can walk and we can talk because the chemistry that makes life possible is much more elaborate and sophisticated than anything we students had ever considered. Proteins make up most of the dry mass of a cell. But instead of a cell dominated by randomly colliding individual protein molecules, 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. […]

  Why do we call the large protein assemblies that underlie cell function protein machines? Precisely because, like the machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts. Within each protein assembly, intermolecular collisions are not only restricted to a small set of possibilities, but reaction C depends on reaction B, which in turn depends on reaction A—just as it would in a machine of our common experience. […]

We have also come to realize that protein assemblies can be enormously complex. … As the example of the spliceosome should make clear, the cartoons thus far used to depict protein machines vastly underestimate the sophistication of many of these remarkable devices.
 1

What Is an Amino Acid Made Of?

As implied by the root of the word (amine), the key atom in amino acid composition is nitrogen. The ultimate source of nitrogen for the biosynthesis of amino acids is atmospheric nitrogen (N2), a nearly inert gas. However, to be metabolically useful, atmospheric nitrogen must be reduced. This process, known as nitrogen fixation, occurs only in certain types of bacteria. Even though nitrogen is one of the most prominent chemical elements in living systems, N2 is almost unreactive (and very stable) because of its triple bond (N≡N). This bond is extremely difficult to break because the three chemical bonds need to be separated and bonded to different compounds. Nitrogenase is the only family of enzymes capable of breaking this bond (i.e., it carries out nitrogen fixation). These proteins use a collection of metal ions as the electron carriers that are responsible for the reduction of N2 to NH3. All organisms can then use this reduced nitrogen (NH3) to make amino acids. In humans, reduced nitrogen enters the physiological system in dietary sources containing amino acids. All organisms contain the enzymes glutamate dehydrogenase and glutamine synthetase, which convert ammonia to glutamate and glutamine, respectively. Amino and amide groups from these two compounds can then be transferred to other carbon backbones by transamination and transamidation reactions to make amino acids. Interestingly, glutamine is the universal donor of amine groups for the formation of many other amino acids as well as many biosynthetic products. Glutamine is also a key metabolite for ammonia storage. All amino acids, with the exception of proline, have a primary amino group (NH2) and a carboxylic acid (COOH) group. They are distinguished from one another primarily by , appendages to the central carbon atom.

the key atom in amino acid composition is nitrogen.

http://www.ck12.org/book/CK-12-Earth-Science-For-High-School/r2/section/18.2/

Nitrogen is also a very important element, used as a nutrient for plant and animal growth. First, the nitrogen must be converted to a useful form. Without "fixed" nitrogen, plants, and therefore animals, could not exist as we know them.

Nitrogenase is the only family of enzymes capable of breaking this bond

http://en.wikipedia.org/wiki/Nitrogenase

The enzyme is composed of the heterotetrameric MoFe protein that is transiently associated with the homodimeric Fe protein. Electrons for the reduction of nitrogen are supplied to nitrogenase when it associates with the reduced, nucleotide-bound homodimeric Fe protein. The heterocomplex undergoes cycles of association and disassociation to transfer one electron, which is the rate-limiting step in nitrogen reduction[citation needed]. ATP supplies the energy to drive the transfer of electrons from the Fe protein to the MoFe protein. The reduction potential of each electron transferred to the MoFe protein is sufficient to break one of dinitrogen's chemical bonds, though it has not yet been shown that exactly three cycles are sufficient to convert one molecule of N2 to ammonia. Nitrogenase ultimately bonds each atom of nitrogen to three hydrogen atoms to form ammonia (NH3), which is in turn bonded to glutamate to form glutamine. The nitrogenase reaction additionally produces molecular hydrogen as a side product.

http://www.spacedaily.com/news/life-03m.html

Nitrogen fixation is one of the most interesting biological processes because it's so difficult to do chemically. Nitrogenase is a very complex enzyme system that actually breaks molecular nitrogen's triple bond,"

http://mbe.oxfordjournals.org/content/21/3/541.long

Still, the origin and extant distribution of nitrogen fixation has been perplexing from a phylogenetic perspective, largely because of factors that confound molecular phylogeny such as sequence divergence, paralogy, and horizontal gene transfer. Here, we make use of 110 publicly available complete genome sequences to understand how the core components of nitrogenase, including NifH, NifD, NifK, NifE, and NifN proteins, have evolved.[/b][/b]

http://www.chem.utoronto.ca/coursenotes/GTM/JM/N2start.htm

Nitrogenase genes are distributed throughout the prokaryotic kingdom, including representatives of the Archaea as well as the Eubacteria and Cyanobacteria.

The enzyme nitrogenase is found in certain bacteria and blue-green algae, which can reduce N2 to NH3 (nitrogen fixation). Some of these bacteria are free-living while others are symbiotic (in the anaerobic environment of roots of legume plants). This bacterial reaction is the key step in the nitrogen cycle, which maintains a balance between two reservoirs of the nitrogen compounds: the Earths atmosphere and the biosphere. The plants cannot extract nitrogen directly from the atmosphere.

Much could be learned from the synthetic models for nitrogenase's cluster and cofactors (their function, mechanism of dinitrogen reduction, possible applications as industrial catalysts etc). However, the design and preparation of such compounds presents a major challenge for synthetic chemists. The most notable examples, described below, come from Holm's research group. Even though nitrogenase has been extensively studied many important questions still remain unanswered, for example: How is the substrate (dinitrogen) binding to the MoFe cofactor? What is the mechanism of dinitrogen reduction?

http://chemwiki.ucdavis.edu/Wikitexts/UC_Davis/UCD_Chem_124A%3A_Berben/Nitrogenase/Nitrogenase_1

There are numerous types of enzymes, complexes, and oNitrogenase.pngther material that operate in living organisms and can be important to their survival. Nitrogenase, shown in Figure 1, is one enzyme that is produced by certain types of bacteria and is vital to their existence and growth. Nitrogenase is a unique enzyme with a crucial function that is distinct to bacteria that utilize it, has unique structure and symmetry, and is sensitive to other compounds that inhibits its functioning. It is “an enzymatic complex which enables fixation of atmospheric nitrogen” [3]. The unique structure of nitrogenase is almost completely known because of the extensive research that has been done on this enzyme. Nitrogenase can also bind to compounds other than nitrogen gas, which can inhibit and decrease its production of ammonia to the rest of the organism’s body. Without proper functioning, the bacteria that utilize nitrogenase would not be able to survive, and other organisms that depend on these bacteria would also die.

Nitrogenase is unique in its ability to fix nitrogen, so that it is more reactive and able to be applied in other reactions that help organisms grow and thrive. David Goodsell states, “Nitrogen is needed by all living things to build proteins and nucleic acids” [4]. However, nitrogen gas, N2, is an inert gas that is stabilized by its triple bond [5], and is difficult for living organisms to use as a source of nitrogen because the molecule’s stability. Nitrogenase is used to separate nitrogen gas, N2, and transforms it into ammonia, NH3 in the reaction:

N2 + 8H+ + 8e- + 16 ATP + 16H2O ----> 2NH3 + H2 + 16ADP + 16Pi

In the form of ammonia organisms have a useable source of nitrogen that is more reactive and can be used to Nitrogenase crystal structure.pngcreate proteins and nucleic acids that are also necessary for the organism. According to the Peters and Szilagyi, “Three types of nitrogenase are known, called molybdenum (Mo) nitrogenase, vanadium (V) nitrogenase and iron-only (Fe) nitrogenase” and the molybdenum nitrogenase,crystal structure shown in Figure 2, is the one that has been studied the most of the three [6]. The nitrogenase enzyme breaks up a diatomic nitrogen gas molecule using a large number of ATP and 8 electrons to create two ammonia molecules and hydrogen gas for each molecule of nitrogen gas [4]. As a result, the bacteria that utilize this enzyme must expend much of their energy, in the form of ATP, so that they will constantly obtain a steady source of nitrogen. Without nitrogenase’s function of fixing nitrogen gas into ammonia, then organisms would not be able to thrive since they would not receive a source of nitrogen for other important reactions.

Many details have been discovered over time about the functioning of nitrogenase, but there has yet to a complete agreement on the structure of nitrogenase. The iron-molybdenum cofactor center of the nitrogenase Molecule structure.pngenzyme consists of iron, sulfur, molybdenum, a homocitrate molecule, a histadine amino acid and a cysteine amino acid [7].

The restrictive functionality of nitrogenase makes it only possible for anaerobic organisms to utilize nitrogenase.

http://creation.com/the-molecular-sledgehammer

The molecular sledgehammer

The amazing story of how scientists struggled for years to duplicate an important bit of chemistry.

Great human inventions are usually recognized, with due fame and honour given to those whose work they are. The awarding of the Nobel Prizes is a yearly reminder to us that great achievements are worthy of recognition and reward.

The light-harnessing ability of the chlorophylls (the chemicals that utilize the sun's energy in green plants) might also find a place of honour. Another tiny but marvellous bit of biochemistry which could be nominated to such a position is a mechanism which might be termed ‘the molecular sledgehammer’.

To appreciate the work done by this ‘sledgehammer’, it is important to understand the role of the element nitrogen in the living world. 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 which 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?

Perhaps this problem can be better appreciated by putting it into terms of human engineering. We need nitrogen for our bodies, to form amino acids and nucleic acids. We must get this nitrogen from our food, whether plant or animal. The animals we eat must rely on plant sources, and the plants must get it from the soil. Nitrogen forms the basis for most fertilizers used in agriculture, both natural and artificial. Natural animal wastes are rich in nitrogen, and it is largely this property that makes them enrich the soil for plant growth. In the late 1800s, a growing population created a great need for nitrogen compounds that could be used in agriculture. At the time, the search for more usable nitrogen was considered a race to stave off Malthusian1 predictions of mass starvation as population outgrew food supply. So chemists wrestled for years with the problem of how to convert the plentiful nitrogen in the air into a form suitable for use in agriculture.

Since naturally occurring, mineable deposits of nitrates were rare, and involved transportation over large distances, an industrial process was greatly needed. Finally, around 1910, a German, Fritz Haber, discovered a workable large-scale process whereby atmospheric nitrogen could be converted to ammonia (NH3). His process required drastic conditions, using an iron-based catalyst with around 1000oF (540oC) heat and about 300 atmospheres of pressure. Haber was given the 1918 Nobel Prize for chemistry because of the great usefulness of his nitrogen-splitting process to humanity.

One might ask, if elemental gaseous nitrogen is such a tough nut to crack, how do atoms of nitrogen ever get into the soil naturally? Some nitrogen is split and added to the soil by lightning strikes. Again, it is a reminder of the force necessary to split the NN bond that the intense heat and electricity of lightning are needed to do it. Still, only a relatively minor amount of nitrogen is added to the Earth’s topsoil yearly by thunderstorms. How is the remainder produced?

The searching chemists of a century ago did not realize that an ingenious method for cracking nitrogen molecules was already in operation. This process did not require high temperatures or pressures, and was already working efficiently and quietly to supply the Earth's topsoil with an estimated 100 million tons of nitrogen every year. This process’ inventor was not awarded a Nobel Prize, nor was it acclaimed with much fanfare as the work of genius that it is. This process is humbly carried on by a few species of the ‘lowest’ forms of life on Earth—bacteria and blue-green algae (Cyanobacteria).

Some of these tiny yet amazingly sophisticated organisms live in symbiosis (mutually beneficial ‘living together’) with certain ‘higher’ plants, known as legumes. The leguminous plants include peas, soybeans and alfalfa, long valued as crops because of their unique ability to enrich the soil. The microbes invade their roots, forming visible nodules in which the process of nitrogen cracking is carried on.

Modern biochemistry has given us a glimpse of the enzyme system used in this process. The chief enzyme is nitrogenase, which, like hemoglobin, is a large metalloprotein complex.2 Like Fritz Haber’s process, and like catalytic converters in cars today, it uses the principle of metal catalysis. However, like all biological enzymatic processes, it works in a more exact and efficient way than the clumsy chemical processes of human invention. Several atoms of iron and molybdenum are held in an organic lattice to form the active chemical site. 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.

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.’4 If one merely substitutes the name of God for the word 'nature', the real picture emerges.

Creationist Christians are often accused of having the same easy answer for any question about specific origin of things in nature: the 'God of the gaps' did it. But this criticism can be easily turned around. What answers do evolutionists give to explain the origin of microscopic marvels like the molecular sledgehammer? They can't explain them scientifically, so they resort to a standard liturgy, worshipping the power of blind chance and natural selection.

One thing is certain—that matter obeying existing laws of chemistry could not have created, on its own, such a masterpiece of chemical engineering. To believe that it was worked out by a wise and caring Creator, who provides all necessary things for the life of His creatures, is far more reasonable than the mystical evolutionary alternative. One grows tired of hearing the same monotonous mantra that ‘we know evolution did it, we just don’t know how.’

Although widely heralded by the press as ‘proving’ that life could have originated on the early earth under natural conditions (i.e. without intelligence), we now realize the experiment actually provided compelling evidence for exactly the opposite conclusion. For example, without all 20 amino acids as a set, most known protein types cannot be produced, and this critical step in abiogenesis could never have occurred.
In addition, equal quantities of both right- and left-handed organic molecules (called a racemic mixture) were consistently produced by the Miller–Urey procedure. In life, nearly all amino acids that can be used in proteins must be left-handed, and almost all carbohydrates and polymers must be right-handed. The opposite types are not only useless but can also be toxic (even lethal) to life.31,32

http://www.bioinfo.org.cn/book/biochemistry/chapt21/sim3.htm

All amino acids are derived from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway (Fig. 21-8 ). Nitrogen enters these pathways by way of glutamate and glutamine. Some pathways are simple, others are not. Ten of the amino acids are only one or a few enzymatic steps removed from their precursors. The pathways for others, such as the aromatic amino acids, are more complex.

Different organisms vary greatly in their ability to synthesize the 20 amino acids. Whereas most bacteria and plants can synthesize all 20, mammals can synthesize only about half of them (see Table 17-1).

Those that are synthesized in mammals are generally those with simple pathways. These are called the nonessential amino acids to denote the fact that they are not needed in the diet. The remainder, the essential amino acids, must be obtained from food. Unless otherwise indicated, the pathways presented below are those operative in bacteria.

A useful way to organize the amino acid biosynthetic pathways is to group them into families corresponding to the metabolic precursor of each amino acid (Table 21-1). This approach is used in the detailed descriptions of these pathways presented below.



http://en.wikipedia.org/wiki/Last_universal_ancestor
The genetic code was composed of three-nucleotide codons, thus producing 64 different codons. Since only 20 amino acids were used, multiple codons code for the same amino acids.

So the biosynthesis and origin of the 20 amino acids must be explained.

How life may have first emerged on Earth: Foldable proteins in a high-salt environment

http://www.sciencedaily.com/releases/2013/04/130405064027.htm

Using a technique called top-down symmetric deconstruction, Blaber's lab has been able to identify small peptide building blocks capable of spontaneous assembly into specific and complex protein architectures. His recent work explored whether such building blocks can be composed of only the 10 prebiotic amino acids and still fold.

His team has achieved foldability in proteins down to 12 amino acids -- about 80 percent of the way to proving his hypothesis.
In 1951, the American Miller succeeded to form organic matter out of a mixture of ammonia (NH3), methane (CH4), hydrogen (H2) and water (H2O) by exposing this mixture to an electric current. During the experiments different organic mixtures were formed, among them amino acids and nucleic acids. These acids are essential for the building of proteins and chromosomes
the theory goes on to imagine the fatty acids polymerize and make lipids. Amino acids polymerize and make peptides. The sugar is polymerizing to make carbohydrates. And purines and pyrimadines are polymerizing to make poly nuclides and RNA (and later DNA).

What the published Miller-Urey experiments did produce were small concentrations of at least 5 amino acids and the molecular constituents of others. The dominant material produced by the experiments was an insoluble carcinogenic mixture of tar—large compounds of toxic mellanoids, a common end product in organic reactions. However, it was recently discovered that the published experiments actually produced 14 amino acids (6 of the 20 fundamentals of life) and 5 amines in various concentrations. In 1952, the technology needed to detect the even smaller trace amounts of prebiotic material was not available. But the unpublished Miller-Urey experiments conducted in that same year show that a modified version of Miller's original apparatus, which increased air flow with a tapering glass aspirator, produced 22 amino acids (still only 6 of the fundamentals) and the same 5 amines.
However, the experiments' parameters and conditions were shown to be incongruent and the results, negative.

The Stanley Miller experiment alone, proves that its scientifically impossible that life could have arose by itself, naturally or randomly from a primordial soup (or any other arrangement and occurrence of chemicals to make polymers... . ) ...
In 1912 a Frenchman, Louis-Camille Maillard discovered-- or actually described the Maillard reaction.
This is a reaction where amino acids interact with reducing sugars, things like glucose and lactose, to produce colors, aromas and flavors characteristic of cooked food. Temperature accelerates this process. When we cut an apple and watch the brown appear after a period of time, thats the Maillard reaction producing melanoids.

When you have reducing sugars along with you have amino acids, they react and produce colored compounds called melanoids: the problem is this reaction that under natural conditions will outcompete any polymerization reaction and essentially BLOCKS the-- the production of biopolymers that are needed in the Abiogenesis theory.

An Evolutionary Perspective on Amino Acids 2



Amino acid metabolism in context. Numerous metabolism pathways are depicted:

central metabolism (in black),
pentose phosphate metabolism (in brown),
nitrogen metabolism (in magenta),
and various amino acid metabolism pathways (all other colors).


Nodes (dots) represent metabolites, and lines represent enzymes and intermediaries. The nitrogen metabolism pathway overlaps with the biosynthesis of arginine and proline, with glutamate as the shared precursor. Histidine biosynthesis branches off the pentose phosphate metabolism. Lysine (AAA) biosynthesis can be synthesized through different pathways, the aminoadipate (AAA) pathway or the diaminopimelate (DAP) pathway (shown in dark blue). There are gene homologies between different biosynthetic pathways. In the dark blue pathways, shaded rectangles represent homologies between enzymes. Similarly, the AAA pathway contains enzymes that share homologies with the branched chain amino acid (BCAA) pathways, whereas the DAP pathway contains homologies with the arginine biosynthetic pathway. In various pathways, homologous enzymes are denoted by shaded rectangles. Different shaded colors indicate different pairs of homologous enzymes.

1) [Bruce Alberts, “The Cell as a Collection of Protein Machines: Preparing the Next Generation of Molecular Biologists,” Cell 92 (1998): 291-294.]
2) http://www.nature.com/scitable/topicpage/an-evolutionary-perspective-on-amino-acids-14568445#
4) http://www.reasons.org/articles/why-these-20-amino-acids
5) https://en.wikibooks.org/wiki/Principles_of_Biochemistry/Amino_acids_and_proteins
6) http://phys.org/news/2013-03-glimpse-evolution-proteins.html
7) http://nideffer.net/proj/Hawking/early_proto/orgel.html
8 ) https://hazen.carnegiescience.edu/sites/default/files/186-ElementsIntro.pdf
9) ASTROBIOLOGY An Evolutionary Approach, page 100
10. The Cell Nature’s First Life-form, page 8

How  biosynthesis of amino acids points to a created process
http://reasonandscience.catsboard.com/t1397-how-biosynthesis-of-amino-acids-points-to-a-created-process



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2 The 22 amino acids required for life on Sat May 09, 2015 8:15 pm

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The 22 amino acids required for life



Paper Reports that Amino Acids Used by Life Are Finely Tuned to Explore "Chemistry Space" 3

A recent paper in Nature's journal Scientific Reports, "Extraordinarily Adaptive Properties of the Genetically Encoded Amino Acids," 2 has found that the twenty amino acids used by life are finely tuned to explore "chemistry space" and allow for maximal chemical reactions. Considering that this is a technical paper, they give an uncommonly lucid and concise explanation of what they did:

[W]e drew 108 random sets of 20 amino acids from our library of 1913 structures and compared their coverage of three chemical properties: size, charge, and hydrophobicity, to the standard amino acid alphabet. We measured how often the random sets demonstrated better coverage of chemistry space in one or more, two or more, or all three properties. In doing so, we found that better sets were extremely rare. In fact, when examining all three properties simultaneously, we detected only six sets with better coverage out of the 108 possibilities tested.
That's quite striking: out of 100 million different sets of twenty amino acids that they measured, only six are better able to explore "chemistry space" than the twenty amino acids that life uses. That suggests that life's set of amino acids is finely tuned to one part in 16 million.
Of course they only looked at three factors -- size, charge, and hydrophobicity. When we consider other properties of amino acids, perhaps our set will turn out to be the best:

While these three dimensions of property space are sufficient to demonstrate the adaptive advantage of the encoded amino acids, they are necessarily reductive and cannot capture all of the structural and energetic information contained in the 'better coverage' sets.
They attribute this fine-tuning to natural selection, as their approach is to compare chance and selection as possible explanations of life's set of amino acids:
This is consistent with the hypothesis that natural selection influenced the composition of the encoded amino acid alphabet, contributing one more clue to the much deeper and wider debate regarding the roles of chance versus predictability in the evolution of life.
But selection just means it is optimized and not random. They are only comparing two possible models -- selection and chance. They don't consider the fact that intelligent design is another cause that's capable of optimizing features. The question is: Which cause -- natural selection or intelligent design -- optimized this trait? Their paper doesn't address that question.
To do so, you'd have to consider the complexity required to incorporate a new amino acid into life's genetic code. That in turn would require lots of steps: a new codon to encode that amino acid, and new enzymes and RNAs to help process that amino acid during translation. In other words, incorporating a new amino acid into life's genetic code is a multimutation feature. As we explain in Appendix D of Discovering Intelligent Design:

The biochemical language of the genetic code uses short strings of three nucleotides (called codons) to symbolize commands -- including start commands, stop commands, and codons that signify each of the 20 amino acids used in life.
After the information in DNA is transcribed into mRNA, a series of codons in the mRNA molecule instructs the ribosome which amino acids are to be strung in which order to build a protein. Translation works by using another type of RNA molecule called transfer RNA (tRNA). During translation, tRNA molecules ferry needed amino acids to the ribosome so the protein chain can be assembled.

Each tRNA molecule is linked to a single amino acid on one end, and at the other end exposes three nucleotides (called an anti-codon). At the ribosome, small free-floating pieces of tRNA bind to the mRNA. When the anti-codon on a tRNA molecule binds to matching codons on the mRNA molecule at the ribosome, the amino acids are broken off the tRNA and linked up to build a protein.

For the genetic code to be translated properly, each tRNA molecule must be attached to the proper amino acid that corresponds to its anticodon as specified by the genetic code. If this critical step does not occur, then the language of the genetic code breaks down, and there is no way to convert the information in DNA into properly ordered proteins. So how do tRNA molecules become attached to the right amino acid?

Cells use special proteins called aminoacyl tRNA synthetase (aaRS) enzymes to attach tRNA molecules to the "proper" amino acid under thelanguage of the genetic code. Most cells use 20 different aaRS enzymes, one for each amino acid used in life. These aaRS enzymes are key to ensuring that the genetic code is correctly interpreted in the cell.

Yet these aaRS enzymes themselves are encoded by the genes in the DNA. This forms the essence of a "chicken-egg problem": aaRS enzymes themselves are necessary to perform the very task that constructs them.

How could such an integrated, language-based system arise in a step-by-step fashion? If any component is missing, the genetic information cannot be converted into proteins, and the message is lost. The RNA world is unsatisfactory because it provides no explanation for how the key step of the genetic code -- linking amino acids to the correct tRNA -- could have arisen.



Mapping Amino Acids to Understand Life’s Origins 1

Only 20 standard amino acids are used to build proteins, but why exactly nature "chose" these particular amino acids is still a mystery. One step towards solving this is to explore the “amino acid space”, the set of possible or hypothetical amino acids that might have been used instead. New research has used computer models to construct a large database of plausible amino acids, revealing thousands of amino acid structures that could have been used.

Building blocks

All organisms on Earth employ the same workforce to perform a wide range of essential biochemical tasks. This workforce is comprised of proteins, which are constructed from a long string of amino acids attached to each other. Even for proteins with particularly long chains of amino acids, there are still only 20 different types of amino acids which are genetically encoded. These amino acids are essentially the building blocks of life, and the same 20 standard amino acids have been used in proteins throughout the history of life on Earth, since the existence of the Last Universal Common Ancestor three to four billions years ago.

Amino acids all have a similar "backbone" structure, which is the foundation upon which the acid is built. This backbone is held together via a single carbon atom acting as a bridge to connect different groups of atoms. Amino acids with a single carbon connector are called alpha amino acids, however it is possible to have more than one carbon atom in the bridge. In this case, they are called beta amino acids and so on.

A group of atoms, called a sidechain, is affixed to the backbone, and it is the structure of the sidechain that differs from one amino acid to the next, creating a staggering amount of variability.

Of course, amino acids don’t just occur in proteins. There are many more that have different biological functions, and some amino acids are also produced abiotically. Some of these abiotic amino acids are not exclusive to the Earth. For instance, the Murchison meteorite was found to be harboring at least 75 amino acids, and it is even thought that the amino acid glycine might exist in the interstellar medium.


The 20 different amino acids will stick together in various formations to form protein.  However, abiotic chemistry can still only account for half of the 20 genetically encoded amino acids, and there are many unanswered questions as to the role amino acids play. Could extraterrestrial life use a different set of amino acids? Why did life on Earth select those particular amino acids? What other amino acids could have been selected? These are all open questions in astrobiology, and one step towards answering them is to gauge the diversity of the amino acids that could have been used for life on Earth.

Defining amino acids

Markus Meringer, Jim Cleaves and Stephen Freeland set about taking this step by attempting to generate a synthetic map of plausible amino acids structures that are similar in size and composition to the 20 genetic amino acids. Up until now, modeling these structures has been hampered due to the complexity in generating so many different chemical structures. However, by taking a different approach to the problem, the scientists were able to draw a preliminary amino acid map.

They input a molecular formula into a computer program that had the capability to visualize different amino acids structures based on this formula. However, computing all possible amino acids is a strenuous task for even the fastest computers. Also, listing every possible amino acid does not narrow down the ones of interest to astrobiology. Therefore the main challenge for the scientists was actually in defining what an amino acid should be, and they used different methods to do this.

Different variations of amino acids

The way to narrow down the interesting amino acids is to explore the "space" around the 20 genetic amino acids. This can be done by generating multiple variations of each amino acid by shuffling the atoms around. For instance, an isomer has the same molecular formula but a different chemical structure, so generating isomers of each amino acid will give the "isomer space".

This isomer space varies in size for each amino acid, partially depending on how many atoms there are in the acid. Therefore, the isomer space is largest around tryptophan, the amino acid with the greatest number of atoms.


The Murchison meteorite has at least 75 amino acids in it.

However, the isomer space is still a lower limit on the number of potential amino acids that could have been available for use in proteins. The isomer space only probes the area in the immediate vicinity of the amino acid, rather than reaching out towards their neighbors to explore the intervening space between formulas. Therefore, the scientists included extra combinations by considering the minimum and maximum numbers of possible atoms for each chemical element. The trick that they applied to do this was to use a "fuzzy formula”.

This means that instead of telling the software that every atom of every chemical element must occur a certain number of times, the fuzzy formula tells the software to be a bit more vague, or "fuzzy", so that the element can have various numbers of atoms. For example, oxygen could be specified as a range from 2 to 4, so that the program would search for solutions that included 2, 3 or 4 oxygen atoms.

Using this fuzzy formula uncovered a treasure trove of additional amino acid combinations. However, a single fuzzy formula can only be used to explore the space around 15 of the amino acids. A single formula that can include all 20 is still too much for current computing power to handle.

Biochemistry’s palette

The next step was to try and explore the amino acid space beyond the isomers while including the five that had been neglected in the previous step. This meant that multiple fuzzy formulas had to be used, but this couldn’t be done without classifying the genetic amino acids into ten different groups.

"There a lot of ways one could classify the coded amino acids according to functional groups and properties," said Jim Cleaves. "But if you stuck to just using the functional groups observed in biology and computationally poked around with that chemical diversity, it wouldn’t be nearly as wide as what we came up with, and it’s clear that biochemistry had a huge palette to play with during evolution."

Using ten fuzzy formulas proved to be the most successful way of exploring the amino acid space. Not only does this method have less processing time than using one fuzzy formula, but it has the advantage of including variations of all of the genetic amino acids.


The “isomer space” shown on the left only explores the space immediately around the amino acids. The second figure shows that using the single “fuzzy formula” explores a much wider space, but cannot account for all amino acids. The final figure shows the amino acid space when multiple fuzzy formulas are used.

Cartography of amino acids

The number of amino acid structures generated surpasses all previous estimates. Using the method with the single fuzzy formula produced 120,000 plausible structures and using ten fuzzy formulas narrows this down to a more biologically relevant set of nearly 4,000 amino acids. This shows that there were a staggering amount of options available that could have possibly been used for building the genetically encoded amino acid set – and yet there are only 20.

They compared the output of both methods to databases of biological alpha amino acids beyond the 20 genetic ones, as well as to amino acids found in carbonaceous meteorites. Many of the amino acids present in the computer library also occur in nature, showing that the computer generation of amino acids is a way of identifying potentially interesting amino acids that could be used in proteins. It is even possible that there are undiscovered natural amino acids that have had their chemical structure probed by the computer database.

The computer libraries generated by the team can now be used as a foundation for further exploration into the jungle of amino acids, and may ultimately lead to an understanding of life’s building blocks.

the biosynthetic pathway leading to many of the more complicated amino acids (e.g., tryptophan) are accordingly far from trivial, involving many enzymes and functionally-integrated biosynthetic pathways.


http://en.wikipedia.org/wiki/Amino_acid_synthesis



A fundamental problem for biological systems is to obtain nitrogen in an easily usable form. This problem is solved by certain microorganisms capable of reducing the inert N≡N molecule (nitrogen gas) to two molecules of ammonia in one of the most remarkable reactions in biochemistry. Ammonia is the source of nitrogen for all the amino acids.

To obtain nitrogen in usable form, you need nitrogen fixation :

http://en.wikipedia.org/wiki/Nitrogen_fixation

Nitrogen fixation, natural and synthetic, is essential for all forms of life because nitrogen is required to biosynthesize basic building blocks of plants, animals and other life forms, e.g., nucleotides for DNA and RNA and amino acids for proteins.

How can this occur :

1) Nitrogen fixation occurs naturally in the air by means of lightning. It forces the combination of nitrogen and oxygen, to produce nitrogen dioxide, which dissolves in rain water to form nitric and nitrous acids, which then combine with compounds in the soil to produce nitrates and nitrites - which are utilisable by plants

the causes of lightning are still not fully understood .

2)Free-Living Heterotrophs
Many heterotrophic bacteria live in the soil and fix significant levels of nitrogen without the direct interaction with other organisms. Examples of this type of nitrogen-fixing bacteria include species of Azotobacter, Bacillus, Clostridium, and Klebsiella.


Associative Nitrogen Fixation
Species of Azospirillum ( bacteria )are able to form close associations with several members of the Poaceae (grasses), including agronomically important cereal crops, such as rice, wheat, corn, oats, and barley.

Nitrogen Fixation
Many microorganisms fix nitrogen symbiotically by partnering with a host plant.

Legume Nodule Formation
The Rhizobium or Bradyrhizobium bacteria colonize the host plant’s root system and cause the roots to form nodules to house the bacteria

By far, the greatest contribution to nitrogen fixation comes from the cyanobacteria.

These bacteria have the ability to take nitrogen from the air, [I wonder how they figured that little trick out???] convert it into their cellular material, and on dying, decompose and make nitrogen available to the soil.

So in the beginning, not only was lack of oxygen a gigantic problem, but the lack of nitrogen was no less so. In order for the anaerobic organisms, whatever they might have been, to generate oxygen in quantity, they simply HAD to have nitrogen in their tissues (as enzymes etc). With nitrogen as unreactive as it is, then how did they fix it? The advanced nitrogen fixers hadn't 'evolved' yet.

http://www.nature.com/scitable/topicpage/an-evolutionary-perspective-on-amino-acids-14568445

The ultimate source of nitrogen for the biosynthesis of amino acids is atmospheric nitrogen (N2), a nearly inert gas. However, to be metabolically useful, atmospheric nitrogen must be reduced. This process, known as nitrogen fixation, occurs only in certain types of bacteria. Even though nitrogen is one of the most prominent chemical elements in living systems, N2 is almost unreactive (and very stable) because of its triple bond (N≡N). This bond is extremely difficult to break because the three chemical bonds need to be separated and bonded to different compounds. Nitrogenase is the only family of enzymes capable of breaking this bond (i.e., it carries out nitrogen fixation).

http://mbe.oxfordjournals.org/content/21/3/541.long

Still, the origin and extant distribution of nitrogen fixation has been perplexing from a phylogenetic perspective.

http://chemwiki.ucdavis.edu/Wikitexts/UC_Davis/UCD_Chem_124A%3A_Berben/Nitrogenase/Nitrogenase_1

Nitrogenase is a unique enzyme with a crucial function that is distinct to bacteria that utilize it, has unique structure and symmetry, and is sensitive to other compounds that inhibits its functioning. It is “an enzymatic complex which enables fixation of atmospheric nitrogen” . The unique structure of nitrogenase is almost completely known because of the extensive research that has been done on this enzyme. Nitrogenase can also bind to compounds other than nitrogen gas, which can inhibit and decrease its production of ammonia to the rest of the organism’s body. Without proper functioning, the bacteria that utilize nitrogenase would not be able to survive, and other organisms that depend on these bacteria would also die.

Nitrogenase is unique in its ability to fix nitrogen, so that it is more reactive and able to be applied in other reactions that help organisms grow and thrive. David Goodsell states, “Nitrogen is needed by all living things to build proteins and nucleic acids” [4]. However, nitrogen gas, N2, is an inert gas that is stabilized by its triple bond [5], and is difficult for living organisms to use as a source of nitrogen because the molecule’s stability. Nitrogenase is used to separate nitrogen gas, N2, and transforms it into ammonia, NH3 in the reaction:

N2 + 8H+ + 8e- + 16 ATP + 16H2O ----> 2NH3 + H2 + 16ADP + 16Pi

In the form of ammonia organisms have a useable source of nitrogen that is more reactive and can be used to create proteins and nucleic acids that are also necessary for the organism. According to the Peters and Szilagyi, “Three types of nitrogenase are known, called molybdenum (Mo) nitrogenase, vanadium (V) nitrogenase and iron-only (Fe) nitrogenase” and the molybdenum nitrogenase,crystal structure shown in Figure 2, is the one that has been studied the most of the three . The nitrogenase enzyme breaks up a diatomic nitrogen gas molecule using a large number of ATP and 8 electrons to create two ammonia molecules and hydrogen gas for each molecule of nitrogen gas . As a result, the bacteria that utilize this enzyme must expend much of their energy, in the form of ATP, so that they will constantly obtain a steady source of nitrogen. Without nitrogenase’s function of fixing nitrogen gas into ammonia, then organisms would not be able to thrive since they would not receive a source of nitrogen for other important reactions.


How could those regulatory machines evolve at precisely the right rate so as to drop into the right place at precisely the right time to effect proper assembly of the nitrogenase machinery?


Fine, L.W., Chemistry Decoded, Oxford University Press, London, pp. 320-330, 1976.

“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”

http://en.wikipedia.org/wiki/Nitrogen_cycle

The plant provides amino acids to the bacteroids so ammonia assimilation is not required and the bacteroids pass amino acids (with the newly fixed nitrogen) back to the plant, thus forming an interdependent relationship

So there we have a classic chicken and egg problem........

many questions on the subject of amino acid synthesis remain. 4 What was the order of appearance of amino acids over evolutionary history? How many amino acids are used in protein synthesis today? How many were present when life began? Were there initially more than twenty used for building blocks, but intense selective process streamlined them down to twenty? Conversely, was the initial set much less than twenty, and did new amino acids successively emerge over time to fit into the protein synthesis repertoire? What are the tempo and mode of amino acid pathway evolution? These questions are waiting to be tackled

HCN and the origin of life 5
Hydrogen cyanide has been discussed as a precursor to amino acids and nucleic acids. For example, HCN is proposed to have played a part in the origin of life.[25] Although the relationship of these chemical reactions to the origin of life theory remains speculative, studies in this area have led to discoveries of new pathways to organic compounds derived from the condensation of HCN


1) http://www.astrobio.net/news-exclusive/mapping-amino-acids-to-understand-lifes-origins/
2) http://www.nature.com/srep/2015/150324/srep09414/full/srep09414.html
3) http://www.evolutionnews.org/2015/06/paper_reports_t096581.html
4) http://www.nature.com/scitable/topicpage/an-evolutionary-perspective-on-amino-acids-14568445
5http://en.wikipedia.org/wiki/Hydrogen_cyanide

More articles:
Synthesis of Aldehydic Ribonucleotide and Amino Acid Precursors by Photoredox Chemistry
Prebiotic synthesis of simple sugars by photoredox systems chemistry



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3 Glycine on Sun May 10, 2015 6:13 am

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Glycine



Glycine symbol Gly or G is the amino acid that has a single hydrogen atom as its side chain. It is the simplest possible amino acid. The chemical formula of glycine is NH2‐CH2‐COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is a colorless, sweet-tasting crystalline solid. It is the only achiral proteinogenic amino acid. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom. The acyl radical is glycyl. 8

Glycine is incorporated during protein biosynthesis in response to four codons—GGU, GGC, GGA, and GGG—and represents approximately 7.2% of the residues of the proteins that have been characterized.   Gly is the simplest amino acid residue, with only a hydrogen atom for a side chain. Note that the a-carbon atom of Gly is not asymmetric, in contrast to the other amino acids incorporated into proteins, because it is bonded to two H atoms. Consequently, this amino acid does not occur as D or L isomers. The absence of a larger side chain gives the polypeptide backbone at Gly residues much greater conformational flexibility than at other residues. 9



The 3-Phosphoglycerate Family of Amino Acids Includes Ser, Gly, and Cys
Serine, glycine, and cysteine are derived from the glycolytic intermediate 3-phosphoglycerate. The diversion of 3-PG from glycolysis is achieved via 3-phosphoglycerate dehydrogenase.  ( figure below ) 
3-Phosphoglyceric acid (3PG) is the conjugate acid of glycerate 3-phosphate (GP). The glycerate is a biochemically significant metabolic intermediate in both glycolysis and the Calvin cycle. 10


Biosynthesis of serine from 3-phosphoglycerate.

This NAD+-dependent oxidation of 3-PG yields 3-phosphohydroxypyruvate—which, as an a-keto acid, is a substrate for transamination by glutamate to give 3-phosphoserine (reaction 2, above). Serine phosphatase then generates serine (Figure above, reaction 3). Serine inhibits the first enzyme, 3-PG dehydrogenase, and thereby feedback-regulates its own synthesis. Glycine is made from serine via two related enzymatic processes. In the first
(Figure a below)



Biosynthesis of glycine from serine
(a) via serine hydroxymethyltransferase and 
(b) via glycine oxidase.

serine hydroxymethyltransferase, a PLP-dependent enzyme, catalyzes the transfer of the serine b-carbon to tetrahydrofolate (THF), the principal agent of one-carbon metabolism . Glycine and N5,N10-methylene-THF are the
products. In addition, glycine can be synthesized by a reversal of the glycine oxidase reaction (Figure b above). Here, glycine is formed when N5,N10-methylene-THF condenses with NH4+ and CO2. Via this route, the b-carbon of serine becomes part of glycine. The conversion of serine to glycine is a prominent means of generating one-carbon derivatives of THF, which are so important for the biosynthesis of purines and the C-5 methyl group of thymine (a pyrimidine ), as well as the amino acid methionine. Glycine itself contributes to both purine and heme synthesis. 11


Glycine is made from serine via two related enzymatic processes. In the first, serine hydroxymethyltransferase, a PLP-dependent enzyme, catalyzes the transfer of the serine b-carbon to tetrahydrofolate (THF), the principal agent of one-carbon metabolism. Glycine and N5,N10-methylene-THF are the products.

Biosynthesis of glycine 6
Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme Serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate:[

Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate 7

Intermediates in energy production pathways such as glycolysis and the Kreb's cycle are commonly the starting point for the biosynthesis of amino acids. The glycolytic intermediate 3-phosphoglycerate is the starting point for the biosynthesis of serine and glycine. First, 3-phosphoglycerate is oxidized and then transaminated to produce 3-phosphoserine. Phosphoserine hydrolase hydrolyzes the phosphate in 3-phosphoserine to produce serine. The side chain carbon of serine is removed to create glycine, which has only hydrogen as its side chain. The removal of the serine side chain is accomplished by transferring the carbon to tetrahydrofolate, a carrier of one-carbon groups. Genetic deficiency of the first enzyme in the pathway, 3-phosphoglycerate dehydrogenase, leads to impaired myelination of neurons and impaired development of the central nervous system.



Intermediates in energy production pathways such as glycolysis and the Kreb's cycle are commonly the starting point for the biosynthesis of amino acids. The glycolytic intermediate 3-phosphoglycerate is the starting point for the biosynthesis of serine and glycine. First, 3-phosphoglycerate is oxidized and then transaminated to produce 3-phosphoserine.

Phosphoserine hydrolase hydrolyzes the phosphate in 3-phosphoserine to produce serine. The side chain carbon of serine is removed to create glycine, which has only hydrogen as its side chain. The removal of the serine side chain is accomplished by transferring the carbon to tetrahydrofolate, a carrier of one-carbon groups. Genetic deficiency of the first enzyme in the pathway, 3-phosphoglycerate dehydrogenase, leads to impaired myelination of neurons and impaired development of the central nervous system.

Phosphoglycerate dehydrogenase
http://en.wikipedia.org/wiki/Phosphoglycerate_dehydrogenase

Phosphoserine transaminase
http://en.wikipedia.org/wiki/Phosphoserine_transaminase

Phosphoserine phosphatase
http://en.wikipedia.org/wiki/Phosphoserine_phosphatase

Serine hydroxymethyltransferase
http://en.wikipedia.org/wiki/Serine_hydroxymethyltransferase

Proposals of prebiotic synthesis of Glycine: 

Under no naturally occurring conditions would any such ratio of amino acids ever exist. In all origin of life laboratory experiments, the amino acids produced in highest ratios are glycine and alanine, the simplest in structure and therefore the most stable of all the amino acids. 5

Synthesis of glycine-containing complexes in impacts of comets on early Earth 1
Delivery of prebiotic compounds to early Earth from an impacting comet is thought to be an unlikely mechanism for the origins of life because of unfavorable chemical conditions on the planet and the high heat from impact. In contrast, we find that impact-induced shock compression of cometary ices followed by expansion to ambient conditions can produce complexes that resemble the amino acid glycine. Our ab initio molecular dynamics simulations show that shock waves drive the synthesis of transient C–N bonded oligomers at extreme pressures and temperatures. On post impact quenching to lower pressures, the oligomers break apart to form a metastable glycine-containing complex. We show that impact from cometary ice could possibly yield amino acids by a synthetic route independent of the pre-existing atmospheric conditions and materials on the planet.

Conclusions Our simulations provide a possible mechanism for the ‘shock synthesis’ of prebiotic molecules on early Earth that is independent of the atmospheric conditions and materials already present on the primitive planet. Novel experiments capable of monitoring complex time-dependent chemical reactivity in shock-compressed systems hold promise to verify this synthetic route. On shock compression, we observed a high degree of chemical reactivity at extreme conditions, with large concentrations of Hþ ions, which create local reducing environments. This reactive environment helps induce the formation of C–N bonded oligomers that contain sequences of C–N bonds equivalent to those of alpha amino acids. On quenching to lower pressures and temperatures, the oligomers break apart to form more stable complexes. Many of these complexes can react easily with Hþ to form glycine. Other exotic, metastable C–N species that we observed in our quenched simulations could conceivably form more complex amino acids or even peptide chains that resemble the proteins needed for the formation of life.

Survivability and reactivity of glycine and alanine in early oceans: effects of meteorite impacts 2
It is so far unknown how meteorite impacts affected amino acids in the early oceans.  The present results also suggest that it will be difficult to produce complicated amino acids under the present impact conditions.  The stabilities of glycine and alanine in aqueous solutions in the process of impact depend not only on pressure and temperature but also on the coexisting chemical species such as ammonia and benzene and minerals such as olivine and hematite.

Comet contains glycine, key part of recipe for life 3
May 27, 2016
An important amino acid called glycine has been detected in a comet for the first time, supporting the theory that these cosmic bodies delivered the ingredients for life on Earth, researchers said Friday.
In addition to the simple amino acid glycine, the instrument also found phosphorus. The two are key components of DNA and cell membranes. "Demonstrating that comets are reservoirs of primitive material in the Solar System, and vessels that could have transported these vital ingredients to Earth, is one of the key goals of the Rosetta mission, and we are delighted with this result."

Panspermia, not a viable explanation for the OOL

1. https://sci-hub.bz/http://www.nature.com/nchem/journal/v2/n11/full/nchem.827.html
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713413/
3. https://phys.org/news/2016-05-comet-glycine-key-recipe-life.html
4. http://reasonandscience.heavenforum.org/t1362-panspermia#1926
5. http://www.truthinscience.org.uk/tis2/index.php/evidence-for-evolution-mainmenu-65/51-the-miller-urey-experiment.html
6. http://en.wikipedia.org/wiki/Glycine
7. http://www.biocarta.com/pathfiles/GlycinePathway.asp
8. https://en.wikipedia.org/wiki/Glycine
9. http://what-when-how.com/molecular-biology/glycine-gly-g-molecular-biology/
10. https://en.wikipedia.org/wiki/3-Phosphoglyceric_acid
11. Biochemistry 6th ed. Garrett, page 907



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4 Alanine on Sun May 10, 2015 9:50 am

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Nonessential Amino Acids Are Synthesized from Common Metabolites
All the nonessential amino acids except tyrosine are synthesized by simple pathways leading from one of four common metabolic intermediates: pyruvate, oxaloacetate, α-ketoglutarate, and 3-phosphoglycerate. Tyrosine, which is really misclassified as being non-essential, is synthesized by the one-step hydroxylation of the essential amino acid phenylalanine. 

Pyruvate, oxaloacetate, and α-ketoglutarate are the α-keto acids (the so-called carbon skeletons) that correspond to alanine, aspartate, and glutamate, respectively. Indeed, the synthesis of each of the amino acids is a one-step transamination reaction ( Reactions 1–3). The ultimate source of the α-amino group in these transamination reactions is glutamate, which is synthesized in microorganisms, plants, and lower eukaryotes by glutamate synthase , an enzyme that is absent in vertebrates. Asparagine and glutamine are, respectively, synthesized from aspartate and glutamate by ATP-dependent amidation.


The syntheses of alanine, aspartate, glutamate, asparagine, and glutamine. 
These reactions involve, respectively, transamination of (1) pyruvate, (2) oxaloacetate, and (3) α-ketoglutarate, and amidation of (4) aspartate and (5) glutamate.

Alanine



So, what about the results of Miller’s experiment?  He obtained a “soup” that contained around 9 amino acids, 2% of the simplest, glycine and alanine, and traces of 7 others. 1

Cytosolic glutamic-pyruvate transaminase (alanine aminotransferase) (GPT) catalyzes the reversible reaction of pyruvate and glutamate to form alanine and 2-oxoglutarate (alpha-ketoglutarate) 6

The pyruvate family of amino acids includes alanine (Ala), valine (Val), and leucine (Leu). 

Glycolysis is the sequence of reactions that metabolizes one molecule of glucose to two molecules of pyruvate with the concomitant net production of two molecules of ATP. This process is anaerobic (i.e., it does not require O2 )

Transamination of pyruvate, with glutamate as amino donor, gives alanine. Because these transamination reactions are readily reversible, alanine degradation occurs via the reverse route, with a-ketoglutarate serving as amino acceptor. Transamination a of pyruvate to alanine is a reaction found in virtually all organisms.



Aspartate, alanine, and glutamate are formed by the addition of an amino group to an alpha-ketoacid
Three a-ketoacids— a-ketoglutarate, oxaloacetate, and pyruvate—can be converted into amino acids in one step through the addition of an amino group. We have seen that a -ketoglutarate can be converted into glutamate by reductive amination

http://en.wikipedia.org/wiki/Alanine#Biosynthesis

Biosynthesis
Alanine can be manufactured in the body from pyruvate and branched chain amino acids such as valine, leucine, and isoleucine.
Alanine is most commonly produced by reductive amination of pyruvate. Because transamination reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. It also arises together with lactate and generates glucose from protein via the alanine cycle.

http://biocyc.org/ECOLI/NEW-IMAGE?type=PATHWAY&object=PWY0-1061

L-alanine is an essential component of protein and peptidoglycan. The latter also contains about three molecules of D-alanine for every L-alanine. Only about 10 percent of the total alanine synthesized flows into peptidoglycan.

At least three pathways (alanine biosynthesis I, alanine biosynthesis II, and alanine biosynthesis III) contribute to the synthesis of alanine. Alanine biosynthesis I is established only by existence of the relevant enzymes. Its contribution to alanine synthesis remains speculative because alanine auxotrophs have not yet been isolated. Because alanine but not valine represses AvtA, its primary purpose is probably synthesis of L-alanine [Falkinham79, Whalen82]. Existence of the Alanine biosyntheis II pathways rests on the evidence that glutamate-pyruvate aminotransferase acitivity is found in crude cell extracts; the enzymes has not been purified nor have mutant alleles of its designated encoding gene (alaB) been isolated [Falkinham79, Raunio73a]. The conversion can also be mediated as a side reaction of alanine racemase [Kurokawa98]. The alanine biosyntheis III pathway, mediated by cysteine desulfurase activity, which is required to donate sulfane sulfur for the synthesis of Fe-S clusters, thiamine, thionucleosides in tRNAs, biotin, lipoic acid, and molybdopterin [Mihara02a], probably contributes only a minor amount of the cell's alanine requirement, as judged by the cell's total requirement for sulfane sulfur.

A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system 3

So, what about the results of Miller’s experiment?  He obtained a “soup” that contained around 9 amino acids, 2% of the simplest, glycine and alanine, and traces of 7 others. 1

Biosynthesis 2
Alanine can be manufactured in the body from pyruvate and branched chain amino acids such as valine, leucine, and isoleucine. Alanine is most commonly produced by reductive amination of pyruvate. Because transamination reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. It also arises together with lactate and generates glucose from protein via the alanine cycle.

http://biocyc.org/ECOLI/NEW-IMAGE?type=PATHWAY&object=PWY0-1061

L-alanine is an essential component of protein and peptidoglycan. The latter also contains about three molecules of D-alanine for every L-alanine. Only about 10 percent of the total alanine synthesized flows into peptidoglycan.

At least three pathways (alanine biosynthesis I, alanine biosynthesis II, and alanine biosynthesis III) contribute to the synthesis of alanine. Alanine biosynthesis I is established only by existence of the relevant enzymes. Its contribution to alanine synthesis remains speculative because alanine auxotrophs have not yet been isolated. Because alanine but not valine represses AvtA, its primary purpose is probably synthesis of L-alanine . Existence of the Alanine biosyntheis II pathways rests on the evidence that glutamate-pyruvate aminotransferase acitivity is found in crude cell extracts; the enzymes has not been purified nor have mutant alleles of its designated encoding gene (alaB) been isolated . The conversion can also be mediated as a side reaction of alanine racemase [Kurokawa98]. The alanine biosyntheis III pathway, mediated by cysteine desulfurase activity, which is required to donate sulfane sulfur for the synthesis of Fe-S clusters, thiamine, thionucleosides in tRNAs, biotin, lipoic acid, and molybdopterin [Mihara02a], probably contributes only a minor amount of the cell's alanine requirement, as judged by the cell's total requirement for sulfane sulfur.






a Transamination, a chemical reaction that transfers an amino group to a ketoacid to form new amino acids. This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential amino acids to nonessential amino acids (amino acids that can be synthesized de novo by the organism). Transamination in biochemistry is accomplished by enzymes called transaminases or aminotransferases. α-ketoglutarate acts as the predominant amino-group acceptor and produces glutamate as the new amino acid. 4

b Auxotrophy (Ancient Greek: "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth 5



1. http://www.truthinscience.org.uk/tis2/index.php/evidence-for-evolution-mainmenu-65/51-the-miller-urey-experiment.html
2. http://en.wikipedia.org/wiki/Alanine#Biosynthesis
3. http://www.drugbank.ca/drugs/DB00160
4. https://en.wikipedia.org/wiki/Transamination
5. https://en.wikipedia.org/wiki/Auxotrophy
6. http://reactome.org/content/detail/R-HSA-70524

further readings:

http://www.uncommondescent.com/intelligent-design/have-glycine-but-no-life/
http://www.evolutionnews.org/2014/06/squeezing_the_l087261.html



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5 Valine on Sun May 10, 2015 9:51 pm

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Valine



Valine is a nonpolar residue. Valine tends to be present in b strands. Valine is essential, that means, in higher mammals, it must be supplied in the diet, since not produced. It is derived from Pyruvate. It is part of the Pyruvate family. 


The pathways of valine and isoleucine synthesis can be considered together because a set of four enzymes is common to the last four steps of both pathways ( see below)



Biosynthesis of valine and isoleucine

Both pathways begin with an a-keto acid a. Isoleucine can be considered a structural analog, and its a-keto acid precursor, namely, a-ketobutyrate, is one carbon longer than the valine precursor, pyruvate. Interestingly, a-ketobutyrate is formed from threonine by threonine deaminase (Figure above, reaction 1). This PLP-dependent enzyme (also known as threonine dehydratase or serine dehydratase) is feedback-inhibited by isoleucine, the end product. Note that part of the carbon skeleton for Ile comes from Asp by way of Thr. From here on, the Val and Ile pathways employ the same set of enzymes. The first reaction involves the generation of hydroxyethyl-thiamine pyrophosphate from pyruvate in a reaction analogous to those catalyzed by transketolase and the pyruvate dehydrogenase complex. The two-carbon hydroxyethyl group is transferred from TPP to the respective keto acid acceptor by acetohydroxy acid synthase (acetolactate synthase) to give a-acetolactate or a-aceto-a-hydroxybutyrate (Figure 25.29, reaction 2). NAD(P)H-dependent reduction of these a-keto hydroxy acids yields the dihydroxy acids a,b-dihydroxyisovalerate and a,b-dihydroxyb- methylvalerate (Figure 25.29, reaction 3). Dehydration of each of these dihydroxy acids by dihydroxy acid dehydratase gives the appropriate a-keto acid carbon skeletons
a-ketoisovalerate and a-keto-b-methylvalerate (Figure above, reaction 4). Transamination by the branched-chain amino acid aminotransferase yields Val or Ile, respectively (Figure above, reaction 5).

Expression of Acetolactate Synthase Enzyme

http://passel.unl.edu/pages/informationmodule.php?idinformationmodule=956592171&topicorder=4&maxto=13

The gene encoding the enzyme acetolactate synthase (ALS) is essential for organisms that need to make their own supply of the amino acids leucine, isoleucine and valine. The ALS enzyme is needed in the cell to catalyze a reaction in the chemical pathway used to make these three amino acids. There are 20 different amino acids making up the subunits of proteins. All proteins are made from differing combinations of the amino acids (Fig. 6,7) Therefore if you are going to make proteins you need to either make amino acids first or consume amino acids in your diet. Animals consume some of their amino acids (the essential amino acids) but plants and bacteria are able make all their own amino acids.

Biosynthesis pathway of Valine:

Pathway Summary from MetaCyc:

The pathway of valine biosynthesis is a four-step pathway that shares all of its steps with the parallel pathway of isoleucine biosynthesis. These entwined pathways are part of the superpathway of leucine, valine, and isoleucine biosynthesis , that generates not only isoleucine and valine, but also leucine.

As a consequence of having several of its component enzymes involved in the synthesis of three different amino acids, the pathway of isoleucine biosynthesis is subject to regulation by all three amino acids. The first step in the pathway is primarily inhibited by valine, along with inhibition by isoleucine and leucine. The potential disruption this might cause to the parallel isoleucine biosynthesis pathway step using the same enzymes is resolved by upregulation of an earlier step that is unique to isoleucine biosynthesis, as explained in the isoleucine biosynthesis I (from threonine) summary. In this way, valine biosynthesis can be regulated independently of isoleucine biosynthesis, despite all four valine biosynthesis enzymes also participating in isoleucine biosynthesis.

http://www.ncbi.nlm.nih.gov/pubmed/12948642

The enzyme activities of the valine biosynthetic pathway and their regulation have been studied in the valine-producing strain, Corynebacterium glutamicum 13032DeltailvApJC1ilvBNCD. In this micro-organism, this pathway might involve up to five enzyme activities: acetohydroxy acid synthase (AHAS), acetohydroxy acid isomeroreductase (AHAIR), dihydroxyacid dehydratase and transaminases B and C.

Acetolactate synthase enzyme

http://www.ebi.ac.uk/interpro/entry/IPR004789

Description
Acetolactate synthases are a group of biosynthetic enzymes apparently found in plants, fungi and bacteria that are capable of de novo synthesis of the branched-chain amino acids [PMID: 16055369]. They can all synthesize acetolactate from pyruvate in the biosynthesis of valine, while some are also capable of synthesizing acetohydroxybutyrate from pyruvate and ketobutyrate during the biosynthesis of isoleucine. These enzymes generally require thiamin diphosphate, FAD and a divalent metal ion for catalysis, though some enzymes specific for acetolactate synthesis do not require FAD. They are composed of two subunits, a large catalytic subunit, and a smaller regulatory subunit which binds the natural modulators (valine, and in some cases leucine or isoleucine).

Since the enzyme is composed of two subunits, its irreducible complex.


Acetohydroxy acid isomeroreductase

http://www.ebi.ac.uk/interpro/entry/IPR013023

catalyses the conversion of acetohydroxy acids into dihydroxy valerates. This reaction is the second in the synthetic pathway of the essential branched side chain amino acids valine and isoleucine [PMID: 9218783]. The enzyme forms a tetramer of similar but non-identical chains, and requires magnesium as a cofactor.

Dihydroxy-acid dehydratase

http://en.wikipedia.org/wiki/Dihydroxy-acid_dehydratase

http://www.ebi.ac.uk/interpro/entry/IPR004404

Two dehydratases, dihydroxy-acid dehydratase (gene ilvD or ILV3) and 6-phosphogluconate dehydratase (gene edd) have been shown to be evolutionary related [PMID: 1624451]. Dihydroxy-acid dehydratase catalyzes the fourth step in the biosynthesis of isoleucine and valine, the dehydratation of 2,3-dihydroxy-isovaleic acid into alpha-ketoisovaleric acid. 6-Phosphogluconate dehydratase catalyzes the first step in the Entner-Doudoroff pathway, the dehydratation of 6-phospho-D-gluconate into 6-phospho-2-dehydro-3-deoxy-D-gluconate. Another protein containing this signature is the Escherichia coli hypothetical protein yjhG. The N-terminal part of the proteins contains a cysteine that could be involved in the binding of a 2Fe-2S iron-sulphur cluster [PMID: 8299945].

a The alpha-keto acids are especially important in biology as they are involved in the Krebs citric acid cycle and in glycolysis.



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6 Leucine and Isoleucine on Mon May 11, 2015 5:11 am

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Leucine


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Leucine biosynthesis involves a five-step conversion process

http://www.biomedcentral.com/1471-2180/9/122

The biosynthesis pathways of the branched-chain amino acids (valine, isoleucine and leucine) all begin with the same precursors (pyruvate or pyruvate and 2-ketobutyrate) and are catalyzed by acetohydroxy acid synthase (AHAS; EC 4.1.3.8 ). The pathways that lead to valine and isoleucine production have four common enzymatic steps. Leucine biosynthesis via the isopropylmalate (IPM) pathway branches from the valine biosynthesis pathway with the conversion of 2-ketoisovalerate and acetyl CoA to α-isopropylmalate. This first committed step of leucine biosynthesis is catalyzed by α-isopropylmalate synthase (α-IPMS; EC 4.1.3.12). The subsequent two steps are catalyzed by isopropylmalate dehydratase and isopropylmalate dehydrogenase. The final step in the production of leucine is catalyzed by an amino transferase enzyme. The IPM pathway may be the primary metabolic route for producing leucine in bacteria, as enzymes in this pathway have been identified in diverse groups of bacteria [1]. The key enzyme of this pathway, α-IPMS, has been isolated and characterized in bacteria [2-4], fungi [5,6] and plants [7,8]. A comparison of α-IPMS from different species shows that there are significant sequence similarities, suggesting that this enzyme is highly conserved [9].




Isoleucine


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Isoleucine is an essential amino acid, only synthesized in plants and bacteria, and required in the diet by animals. In proteins, the hydrophobic isoleucine side-chain tends to reside with other hydrophobic residues in the interior of globular proteins or in transmembrane domains. Isoleucine biosynthesis begins with the common metabolic intermediate pyruvate, the endpoint of glycolysis. The first step in isoleucine biosynthesis requires thiamine pyrophosphate to form a carbanion intermediate. Another component comes from the amino acid threonine, which is deaminated to produce alpha-ketobutyrate. Alpha-ketobutyrate and the TPP intermediate react to produce alpha-aceto-alpha-hydroxybutyrate that is isomerized, reduced and dehydrated to create alpha-keto-beta-methylvalerate. In the last step, valine aminotransferase transfers an amino group from glutamate to produce isoleucine. The isoleucine pathway is almost the same as the valine biosynthesis pathway, using the same enzymes, and varying primarily at the first step in the pathway. As a key enzyme in the synthesis of leucine, isoleucine and valine, acetolactate synthase is the target of several herbicides and mutation of this enzyme is responsible in some cases for the development of herbicide resistance.



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7 Methionine on Sat Jun 27, 2015 2:34 pm

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Methionine

.

The Oxaloacetate Family of Amino Acids Includes Asp, Asn, Lys, Met, Thr, and Ile
The members of the oxaloacetate family of amino acids include aspartate (Asp), asparagine (Asn), lysine (via the diaminopimelic acid pathway), methionine (Met), threonine (Thr), and isoleucine (Ile). Threonine, methionine, and lysine biosynthesis in bacteria proceeds from the common precursor aspartate, which is converted first to aspartyl-b-phosphate and then to b-aspartyl-semialdehyde. The first reaction is an ATP-dependent phosphorylation catalyzed by aspartokinase. (Figure below, reaction 1).

Folate, vitamin B12  is reduced to methyl-THF which used to methylate homocysteine to form methionine, a reaction which is catalyzed by a B12-containing methyltransferase.  


Biosynthesis of threonine, methionine, and lysine, members of the aspartate family of amino acids 2


In bacteria, aspartate is the common precursor of lysine, methionine, and threonine. 


The biosynthesis of the aspartate family of amino acids: lysine, methionine, and threonine. 
The pathway enzymes shown are 
(1) aspartokinase, 
(2) β-aspartate semialdehyde dehydrogenase, 
(3) homoserine dehydrogenase, and 
(4) methionine synthase (a coenzyme B12–dependent enzyme) 1


1. Fundamentals of Biochemistry, 6th ed. page 753
2. Biochemistry 6th ed. Garrett, page 901
3. https://www.ncbi.nlm.nih.gov/pubmed/11813080



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8 Proline on Sun Jun 28, 2015 7:29 am

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The a-Ketoglutarate Family of Amino Acids Includes Glu, Gln, Pro, Arg, and Lys

Amino acids derived from a-ketoglutarate include glutamate (Glu), glutamine (Gln), proline (Pro), arginine (Arg), and in fungi and protista such as Euglena, lysine (Lys). Proline is derived from glutamate via a series of four reactions involving activation, then reduction, of the g-carboxyl group to an aldehyde (glutamate-5-semialdehyde), which spontaneously cyclizes to yield the internal Schiff base, D1-pyrroline-5-carboxylate. NADPH-dependent reduction of the pyrroline double bond gives proline.


The pathway of proline biosynthesis from glutamate.
The enzymes are (1) g-glutamyl kinase, (2) glutamate-5-semialdehyde dehydrogenase, and (4) D1-pyrroline-5-carboxylate reductase; reaction (3) occurs nonenzymatically.



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9 Phenylalanine on Wed Nov 11, 2015 11:23 am

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Phenylalanine







The biosynthesis of phenylalanine

The aromatic amino acids, phenylalanine, tyrosine, and tryptophan, are derived from a shared pathway that has chorismic acid as a key intermediate. Indeed, chorismate is common to the synthesis of cellular compounds having benzene rings. At chorismate, the pathway separates into three branches, each leading specifically to one of the aromatic amino acids. The branches leading to phenylalanine and tyrosine both pass through prephenate.

Phenylalanine, as its name indicates, contains a phenyl ring attached in place of one of the hydrogen atoms of alanine. Phenylalanine, tyrosine, and tryptophan are synthesized by a common pathway.

Among the essential amino acids, the aromatic amino acids (phenylalanine, tyrosine, and tryptophan) form by a pathway in which chorismate occupies a key branch point.

The Escherichia coli bifunctional P-protein prephenate dehydratase (PDT) , which plays a central role in L-phenylalanine (Phe) biosynthesis, contains distinct chorismate mutase (CM) and prephenate dehydratase (PDT) domains as well as a regulatory (R) domain for feedback control by Phe.  1

1. https://www.ncbi.nlm.nih.gov/pubmed/10769128



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10 Tryptophan on Sat Oct 07, 2017 3:31 pm

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Tryptophan


Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a non-polar aromatic amino acid. It is essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet 8




Free-living bacteria synthesize tryptophan (Trp), which is an essential amino acid for mammals, some plants, and lower eukaryotes. The Trp synthesis pathway appears to be highly conserved, and the enzymes needed to synthesize tryptophan are widely distributed across the three domains of life. This pathway is one of three that compose aromatic amino acids from chorismate.   As another point of distinction, the Trp pathway is the most biochemically expensive of the amino acid pathways, and for this reason it is expected to be tightly regulated.   7

Tryptophan biosynthesis



Glycolysis produces phosphoenolpyruvate (PEP) and erythrose- 4-phosphate, which produce chorismate, which produces Tryptophan ( Red pathway, above) 

Tryptophan (Trp) biosynthesis is a biologically expensive, complicated process. In fact, the products of four other pathways are essential contributors of carbon or nitrogen during tryptophan formation. Thus, the principal pathway precursor, chorismate, is also the precursor of the other aromatic amino acids, phenylalanine and tyrosine, as well as serving as the precursor of paminobenzoic acid and several other metabolites. In addition, glutamine, phosphoribosylpyrophosphate, and L-serine contribute nitrogen and/or carbon during tryptophan formation. 3

The Aromatic Amino Acids Phenylalanine, Tyrosine, and Tryptophan Are Synthesized from Glucose Derivatives. The precursors of the aromatic amino acids are the glycolytic intermediate phosphoenolpyruvate (PEP) and erythrose- 4-phosphate (an intermediate in the pentose phosphate pathway



Chorismate Is Synthesized from PEP and Erythrose-4-P 
Chorismate biosynthesis occurs via the shikimate pathway


The shikimate pathway leading to the synthesis of chorismate.

The precursors for this pathway are the common metabolic intermediates phosphoenolpyruvate (PEP) and erythrose-4-phosphate. These intermediates are linked to form 3-deoxy-d-arabino-heptulosonate-7-phosphate (DAHP) by DAHP synthase (Figure above reaction 1). Although this reaction is remote from the ultimate aromatic amino acid end products, it is an important point for regulation of aromatic amino acid biosynthesis, as we shall see. In the next step on the way to chorismate, DAHP is cyclized to form a six-membered saturated ring compound, 5-dehydroquinate (Figure above, reaction 2), in a reaction catalyzed by 3-dehydroquinate synthase (NAD+ is a coenzyme in this reaction but is not modified by it). A sequence of reactions ensues that introduces unsaturations into the ring through dehydration (Figure above, reaction 3, 5-dehydroquinate dehydratase ) and reduction (reaction 4, shikimate dehydrogenase), yielding shikimate. Phosphorylation of shikimate by shikimate kinase (reaction 5), then addition of PEP by 3-enolpyruvylshikimate-5-phosphate synthase (reaction 6), followed by chorismate synthase (reaction 7), gives chorismate. Thus, two equivalents of PEP are needed to form chorismate from erythrose-4-P.

1. DAHP synthase
2. 3-dehydroquinate synthase
3. 5-Dehydroquinate Synthetase
4. Shikimate dehydrogenase
5. Shikimate kinase
6. 3-enolpyruvylshikimate-5-phosphate synthase
7. Chorismate synthase

The pathway of tryptophan synthesis is perhaps the most thoroughly studied of any biosynthetic sequence, particularly in terms of its genetic organization and expression. Synthesis of Trp from chorismate requires six steps


The Aromatic Amino Acids Are Synthesized from Chorismate
The aromatic amino acids, phenylalanine, tyrosine, and tryptophan, are derived from a shared pathway that has chorismic acid (Figure below) as a key intermediate.


Some of the aromatic compounds derived from chorismate.

Indeed, chorismate is common to the synthesis of cellular compounds having benzene rings, including these amino acids, the fat-soluble vitamins E and K, folic acid, and coenzyme Q and plastoquinone (the two quinones necessary to electron transport during respiration and photosynthesis, respectively). Lignin, a polymer of nine-carbon aromatic units, is also a derivative of chorismate. Lignin and related compounds can account for as much as 35% of the dry weight of higher plants; clearly, enormous amounts of carbon pass through the chorismate biosynthetic pathway.

Enzymes and reactions in the Tryptophan biosynthesis pathway:

Tryptophan is synthesized in five steps from chorismate. Each step requires a specific enzyme activity. The four intermediates between chorismate and tryptophan serve no function other than as precursors of tryptophan.

That means, these enzymes have no other purpose, and could not have been co-opted from other synthesis pathways. Their exclusive and necessity in intermediate stages make them irreducible, and the pathway as a whole is irreducibly complex. 




6. Anthranilate synthase
7. Anthranilate phosphoribosyltransferase
8. Phosphoribosylanthranilate isomerase
9. Indole-3-glycerol-phosphate synthase
10 + 11. Tryptophan synthase




The biosynthesis of phenylalanine, tyrosine, and tryptophan from chorismate.

In most microorganisms, the first enzyme, anthranilate synthase (see Figure above, reaction 6), with the b-subunit acting in a glutamine–amidotransferase role to provide the ONH2 group of anthranilate. Or, given high levels of ammonium NH4+, the a-subunit can carry out the formation of anthranilate directly by a process in which the activity of the b-subunit is unnecessary. Furthermore, in certain enteric bacteria, such as E. coli and Salmonella typhimurium, the second reaction of the pathway, the phosphoribosyl-anthranilate transferase reaction (see above, reaction 7), is an activity catalyzed by the a-subunit of anthranilate synthase. PRPP (5-phosphoribosyl-1-pyrophosphate), the substrate of this reaction, is also a precursor for purine biosynthesis. Phosphoribosyl-anthranilate then undergoes a rearrangement wherein the ribose moiety is isomerized to the ribulosyl form in enol-1-(o-carboxyphenylamino)-1-deoxyribulose-5-phosphate by N-(59-phosphoribosyl)-anthranilate isomerase (see Figure aboce, reaction 8 ). Decarboxylation and ring closure ensue to yield the indole nucleus as indole-3-glycerol phosphate (indole-3-glycerol phosphate synthase, reaction 9). The final two reactions (10 and 11 in Figure above) are both catalyzed by tryptophan synthase. The a-subunit cleaves indoleglycerol-3-phosphate to form indole and 3-glycerol phosphate. The indole is then passed to the b-subunit, which adds serine in a PLP-dependent reaction. The active sites of the a- and b-subunits are separated from each other by 2.5 nm but are connected by a hydrophobic tunnel wide enough to accommodate indole (Figure below).

The bacterial tryptophan synthases are multienzyme nanomachines that catalyze the last two steps in L-tryptophan biosynthesis. 4


The tryptophan synthase nanomachine structure and catalytic reactions. 
The tryptophan synthase a2b2 bienzyme complex catalyzes the final steps in L-tryptophan biosynthesis. Efficiency is achieved by channeling indole between the a- and b-subunit active sites through a long interconnecting tunnel.  (a) Ribbon model of the closed abdimeric unit of the tryptophan synthase a2b2 tetramer with D,L-glycerol 3-phosphate (GP) bound to the a-site and a-aminoacrylate (A-A) bound to the b-site. The approximate location of the interconnecting tunnel through which substrate indole is channeled is shown by the broken green line. Color scheme: the a-subunit is gold with the loop aL6 (magenta) folded down over loop aL2 (red), closing the a-site; the b-subunit is yellow with the COMM domain blue and helix bH6 of the COMM domain dark blue; the MVC site is shown as a magenta sphere, and the water molecule (wat88) poised for reaction with E(A-A) is the red sphere; key catalytic residues (aGlu49, aAsp60, bLys87 and bGlu109) and residues involved in the allosteric switch for interconversion of open and closed conformations (bArg141 and bAsp305) and the active-site ligands [GP and E(A-A)] are shown in sticks with CPK coloring. The white broken line indicates the salt bridge that is characteristic of the closed b-subunit conformation formed between bArg141 and bAsp305. (b,c) organic chemistry of the a- and b-reactions. At the a-site, IGP is cleaved, yielding indole and G3P. At the b-siteL-Ser reacts with pyridoxal 50 -phosphate bound in the form of the Schiff-base internal aldimine, E(Ain), formed with bLys87 in stage I to yield intermediates E(GD1), E(Aex1), E(Q1) and E(A-A). In stage II, indole, produced at the asite, is channeled to the b-site via the 25-A˚ -long tunnel, where it reacts with E(A-A) to yield the E(Q2), E(Q3), E(Aex2) and E(GD2) intermediates.

Thus, indole, the product of the reaction catalyzed by the a-subunit (see reaction 10), can be transferred directly to the b-subunit, which catalyzes condensation with serine to yield Trp (see reaction 11). Thus, indole is not lost from the enzyme complex and diluted in the surrounding milieu. This phenomenon of direct transfer of enzyme-bound metabolic intermediates, or tunneling, increases the efficiency of the overall pathway by preventing loss and dilution of the intermediate.

Origins of Life on the Earth and in the Cosmos SECOND EDITION, page 291 describes the pathway as follows:
The first specific step in tryptophan biosynthesis is the glutamine-dependent conversion of chorismate to the simple aromatic compound anthranilate. Like most other glutamine-dependent reactions, this reaction also can occur with ammonia as the source of the amino group. However, high concentrations of ammonia are required. Thus far, almost all the anthranilate ligases examined have the glutamine amidotransferase activity (component II) and the chorismate-to-anthranilate activity (component I) on separate proteins. Anthranilate is transferred to a ribose phosphate chain in a phosphoribosylpyrophosphate- dependent reaction catalyzed by anthranilate phosphoribosyltransferase. Phosphoribosyl anthranilate undergoes a complex reaction known as the Amadori rearrangement, in which the ribosyl moiety becomes a ribulosyl moiety. The product, 1-(O-carboxylphenylamino)-1-deoxyribulose-5-phosphate, is cyclized to indole-glycerol phosphate by removal of water and loss of the ring carboxyl by indoleglycerol phosphate ligase. The final step in tryptophan biosynthesis is a replacement reaction, catalyzed by tryptophan ligase, in which glyceraldehyde-3-phosphate is removed from indole-glycerol phosphate and the enzyme-bound indole undergoes a -replacement reaction with serine.

If the conversion of chorismate to tryptophan takes place in five steps, there must be four intermediates between chorismate and tryptophan. If the third step is regulated, this would lead to an awkward situation in which an intermediate might accumulate. This would occur under conditions where the end product tryptophan was present in adequate amounts to satisfy metabolic needs. This would be a wasteful process and might even lead to complications if the metabolic intermediate at high concentrations were toxic.

Origin of Tryptophan biosynthesis and abiotic scenarios
Aromatic amino acid biosynthesis proceeds via a long series of reactions, most of them concerned with the formation of the aromatic ring before branching into the specific routes to phenylalanine, tyrosine, and tryptophan. Chorismate, the common intermediate of the three aromatic amino acids, is derived in eight steps from erythrose-4-phosphate and phosphoenolpyruvate.

How Structure Arose in the Primordial Soup
Tryptophan, in comparison, has a complex structure and is comparatively rare in the protein code, like a Y or Z, leading scientists to theorize that it was one of the latest additions to the code. 6


How Structure Arose in the Primordial Soup
May 19, 2015
In research published online in March in the Journal of Molecular Evolution, Fournier showed that the last chemical letter added to the code was a molecule called tryptophan 2

Ancestral Reconstruction of a Pre-LUCA Aminoacyl-tRNA Synthetase Ancestor Supports the Late Addition of Trp to the Genetic Code.
2015 Mar 20
The genetic code was likely complete in its current form by the time of the last universal common ancestor (LUCA). Several scenarios have been proposed for explaining the code’s pre-LUCA emergence and expansion, and the relative order of the appearance of amino acids used in translation. One co-evolutionary model of genetic code expansion proposes that at least some amino acids were added to the code by the ancient divergence of aminoacyl-tRNA synthetase (aaRS) families. 

It is important to remark that secular science puts the origin and appearance of amino acids prior to LUCA. That said, it's clear that any allusion to evolution is prohibited by the fact that there was no evolution prior to DNA replication.

1. https://www.ncbi.nlm.nih.gov/pubmed/25791872
2. https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/
3. http://2009.igem.org/wiki/images/a/a7/The_tryptophan_biosynthetic_pathway.pdf
4. http://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/18486479
5. Origins of Life on the Earth and in the Cosmos SECOND EDITION, page 117
6. https://www.scientificamerican.com/article/how-structure-arose-in-the-primordial-soup/
7. https://www.nature.com/scitable/topicpage/an-evolutionary-perspective-on-amino-acids-14568445
8. https://en.wikipedia.org/wiki/Tryptophan



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11 Serine on Sat Oct 07, 2017 6:55 pm

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Serine


The biosynthesis of serine starts with the oxidation of 3-phosphoglycerate (an intermediate from glycolysis) to 3-phosphohydroxypyruvate and NADH by phosphoglycerate dehydrogenase (EC 1.1.1.95). Reductive amination (transamination) of this ketone by phosphoserine transaminase (EC 2.6.1.52) yields 3-phosphoserine (O-phosphoserine) which is hydrolyzed to serine by phosphoserine phosphatase


The 3-Phosphoglycerate Family of Amino Acids Includes Ser, Gly, and Cys
Serine, glycine, and cysteine are derived from the glycolytic intermediate 3-phosphoglycerate. The diversion of 3-PG from glycolysis is achieved via 3-phosphoglycerate dehydrogenase (Figure 25.31, reaction 1). This NAD1-dependent oxidation of 3-PG yields 3-phosphohydroxypyruvate—which, as an a-keto acid, is a substrate for transamination by glutamate to give 3-phosphoserine (Figure 25.31, reaction 2). Serine phosphatase then generates serine (Figure 25.31, reaction 3). Serine inhibits the first enzyme, 3-PG dehydrogenase, and thereby feedback-regulates its own synthesis.

The three enzymes used in the pathway: 

Phosphoglycerate dehydrogenase
Phosphoserine transaminase
phosphoserine phosphatase




Biosynthesis of serine from 3-phosphoglycerate.



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12 Threonine on Sun Dec 03, 2017 4:48 am

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Threonine

Threonine, methionine, and lysine biosynthesis in bacteria proceeds from the common precursor aspartate, which is converted first to aspartyl-b-phosphate and then to b-aspartyl semialdehyde. The first reaction is an ATP-dependent phosphorylation catalyzed by aspartokinase (Figure below, reaction 1)



Biosynthesis of threonine,  member of the aspartate family of amino acids.

Methionine synthase (alternatively homocysteine methyltransferase) catalyzes the methylation of homocysteine to form methionine using N5-methyl-THF as its methyl group donor.



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13 Asparagine on Sat Jan 06, 2018 8:40 am

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Asparagine

Asparagine is formed by amidation of the b-carboxyl group of aspartate. In bacteria, in analogy with glutamine synthesis, the nitrogen added in this amidation comes directly from NH4+. In other organisms, asparagine synthetase catalyzes the ATP-dependent transfer of the amido-N of glutamine to aspartate to yield glutamate, AMP, PPi, and asparagine.



Asparagine biosynthesis from Asp, Gln, and ATP by asparagine synthetase. b-Aspartyladenylate is an enzyme-bound intermediate.


Asparagine and glutamine are, respectively, synthesized from aspartate and glutamate by ATP-dependent amidation. Aspartate amidation by asparagine synthetase to form asparagine follows a different route; it uses glutamine as its amino group donor and cleaves ATP to AMP + PPi. 


The syntheses of asparagine


Asparagine synthetase B dimer, E.Coli



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14 Glutamine on Wed Jan 24, 2018 11:05 am

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Glutamine

Amino acids derived from a-ketoglutarate include glutamate (Glu), glutamine (Gln), proline (Pro), arginine (Arg), and in fungi and protista such as Euglena, lysine (Lys). Pyruvate, oxaloacetate, and α-ketoglutarate are the α-keto acids (the so-called carbon skeletons) that correspond to alanine, aspartate, and glutamate, respectively. Indeed, the synthesis of
each of the amino acids is a one-step transamination reaction. 


The syntheses of  glutamine.

The ultimate source of the α-amino group in these transamination reactions is glutamate, which is synthesized in microorganisms, plants, and lower eukaryotes by glutamate synthase enzyme that is absent in vertebrates.


Glutamine synthetase (GS) catalyzes the ATP-dependent amidation a of the g-carboxyl group of glutamate to form glutamine. 


(a) The enzymatic reaction catalyzed by glutamine synthetase. 
(b) The reaction proceeds by (a) activation of the g-carboxyl group of Glu by ATP, followed by (b) amidation by NH4+.

The reaction proceeds via a g-glutamyl-phosphate intermediate, and GS activity depends on the presence of divalent cations such as Mg2+. Glutamine is a major Nitrogen donor in the biosynthesis of many organic N compounds such as purines, pyrimidines, and other amino acids, and GS activity is tightly regulated. The amide-N of glutamine provides the nitrogen atom in these biosyntheses. Glutamine is the most abundant amino acid in humans.
Carbamoyl-phosphate synthetase I, the third enzyme capable of using ammonium to form an N-containing organic compound, catalyzes an early step in the urea cycle. Two ATPs are consumed, one in the activation of bicarbonate HCO3+ for reaction with ammonium and the other in the phosphorylation of the carbamate formed. N-acetylglutamate is an essential allosteric activator for this enzyme. Both carbamoyl-P and N-acetylglutamate are precursors to arginine synthesis and intermediates in the urea cycle.



a Any derivative of an oxoacid in which the hydroxyl group has been replaced with an amino or substituted amino group; especially such derivatives of a carboxylic acid, the carboxamides. 1

1. https://en.wiktionary.org/wiki/amide



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15 Tyrosine on Thu Jan 25, 2018 12:58 pm

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Tyrosine



Tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese  2

The Aromatic Amino Acids Are Synthesized from Chorismate
The aromatic amino acids, phenylalanine, tyrosine, and tryptophan, are derived from a shared pathway that has chorismic acid as a key intermediate.(Figure below)


Some of the aromatic compounds derived from chorismate.

Indeed, chorismate is common to the synthesis of cellular compounds having benzene rings. a

The Aromatic Amino Acids Phenylalanine, Tyrosine, and Tryptophan Are Synthesized from Glucose Derivatives
In plants and bacteria, tyrosine is synthesized from chorismate in pathways much less complex than the tryptophan pathway. The precursors of the aromatic amino acids are the glycolytic intermediate phosphoenolpyruvate (PEP) and erythrose- 4-phosphate (an intermediate in the pentose phosphate pathway). Their condensation forms 2-keto-3-deoxy-D-arabinoheptulosonate-7-phosphate. This C7 compound cyclizes and is ultimately converted to chorismate, the branch point for tryptophan synthesis. Chorismate is converted to either anthranilate and then to tryptophan, or to prephenate and on to tyrosine.



The biosynthesis of tyrosine
The enzymes in the pathway are 
(1) 2-keto-3-deoxy-D-arabinoheptulosonate-7-phosphate synthase 
(5) chorismate mutase


Synthesis of  tyrosine 
Chorismate can be converted into prephenate, which is subsequently converted into tyrosine.

A mutase converts chorismate into prephenate, the immediate precursor of the aromatic ring of phenylalanine and tyrosine. This fascinating conversion is a rare example of an electrocyclic reaction in biochemistry, mechanistically similar to the well-known Diels–Alder reaction in organic chemistry. Dehydration and decarboxylation yield phenylpyruvate. Alternatively, prephenate can be oxidatively decarboxylated to p- hydroxyphenylpyruvate. These a -ketoacids are then transaminated to form tyrosine.


Biosynthesis of tyrosine from chorismate in bacteria and plants. Conversion of chorismate to prephenate is a rare biological example of a Claisen rearrangement.

Chorismate mutase
In enzymology, chorismate mutase is an enzyme that catalyzes the chemical reaction for the conversion of chorismate to prephenate in the pathway to the production of phenylalanine and tyrosine, also known as the shikimate pathway. Hence, this enzyme has one substrate, chorismate, and one product, prephenate. Chorismate mutase is found at a branch point in the pathway. The enzyme channels the substrate, chorismate to the biosynthesis of tyrosine and phenylalanine and away from tryptophan. Its role in maintaining the balance of these aromatic amino acids in the cell is vital.This is the single known example of a naturally occurring enzyme catalyzing a pericyclic reaction 3

Chorismate mutase is the only well-characterized enzyme that catalyzes a pericyclic process and has thus generated considerable interest in the bioorganic circles. Despite extensive studies, however, the enzyme mechanism and in particular the million-fold rate acceleration by chorismate mutase has remained poorly understood. 4 

Prephenate dehydrogenase
Prephenate dehydrogenase (PD) is a member of the TyrA protein family involved in the biosynthesis of L-tyrosine. This enzyme catalyzes the oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate (HPP) in the presence of NAD+. This conversion, along with the rearrangement of chorismate to prephenate catalyzed by chorismate mutase (CM), constitutes two consecutive reactions that are essential for tyrosine biosynthesis in many bacteria and other microorganisms, yeast, and fungi .  5

a Benzene is an important organic chemical compound with the chemical formula C6H6. The benzene molecule is composed of six carbon atoms joined in a ring with one hydrogen atom attached to each. As it contains only carbon and hydrogen atoms, benzene is classed as a hydrocarbon.  1

1. https://en.wikipedia.org/wiki/Benzene
2. https://en.wikipedia.org/wiki/Tyrosine#Biosynthesis
3. https://en.wikipedia.org/wiki/Chorismate_mutase
4. https://www.mn.uio.no/kjemi/english/research/projects/chorismate-mutase/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265095/



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16 Cysteine on Wed Apr 11, 2018 2:42 pm

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Cysteine biosynthesis

In animals, biosynthesis begins with the amino acid serine. The sulfur is derived from methionine, which is converted to homocysteine through the intermediate S-adenosylmethionine. Cystathionine beta-synthase then combines homocysteine and serine to form the asymmetrical thioether cystathionine. The enzyme cystathionine gamma-lyase converts the cystathionine into cysteine and alpha-ketobutyrate. In plants and bacteria, cysteine biosynthesis also starts from serine, which is converted to O-acetylserine by the enzyme serine transacetylase. The enzyme O-acetylserine (thiol)-lyase, using sulfide sources, converts this ester into cysteine, releasing acetate. 11 

Cysteine is hydrophobic, and unique among the 20 amino acids in that it has a thiol group that can form a disulfide bond with another cysteine through the oxidation of the two thiol groups


Disulfide-bonded cysteine residues. 
The disulfide bond forms when the two thiol groups are oxidized. An important amino acid side-chain reaction is the formation of disulfide bonds via reaction between two cysteines. In proteins, cysteine residues form disulfide linkages that stabilize protein structure






Cysteine biosynthesis
Serine, Cysteine, and Glycine Are Derived from 3-Phosphoglycerate. In animals, cysteine is synthesized from serine and homocysteine, a breakdown product of methionine. Since cysteine’s sulfhydryl group is derived from the essential amino acid methionine, cysteine can be considered to be an essential amino acid. 12


Cysteine synthesis: Reactions 5 and 6

Cysteine biosynthesis is the metabolic link between sulfur assimilation and the myriad of sulfur-containing molecules in the cell. For example, this pathway provides essential metabolites for production of glutathione, a key regulatory agent of intracellular redox environment during abiotic and biotic stresses. 

10


9



The serine family includes three amino acids: serine, glycine, and cysteine (see Figure below). 6



Cysteine synthesis funnels sulfur into the biochemical world and supplies the cysteine needed for biosynthesis. 
The biosynthesis of L-cysteine entails the sulfhydryl transfer to an activated form of serine. In the first step an acetyl group is transferred from acetyl-coenzyme A (acetyl-CoA) to serine to yield O-acetylserine .

An acetyl group is transferred from acetyl-coenzyme A (acetyl-CoA) to serine to yield O-acetylserine. The reaction is catalyzed by Serine O-acetyltransferase. in a second step, cysteine is catalyzed by a second enzyme,  Cysteine synthase 



The reaction is catalyzed by Serine O-acetyltransferase. 



The N-terminal domain of the protein Serine acetyltransferase helps catalyze acetyl transfer. This particular enzyme catalyzes serine into cysteine. Of particular interest to scientists, is the ability to harness the natural ability of the enzyme, Serine acetyltransferase, to create nutritionally essential amino acids 7 and 8

The formation of cysteine itself is catalyzed by O-acetylserine sulfhydrylase ( Cysteine synthase ) 


Ribbon representation of the structure of OASS-A. ( O-acetylserine sulfhydrylase. ) 
Left, the dimer of OASS-A with PLP in space-filling representation. A molecular 2-fold axis runs from the lower left to the upper right of the molecule. Right, a monomer of OASS-A is shown. The two-domain nature of the structure is shown with the central, twisted -sheet in both domains surrounded by helices. The entry to the active site is on the left of the monomer. 

In the Archean world before the advent of atmospheric oxygen, most sulfur was probably present in the reduced state amenable to direct incorporation into cysteine. Currently, most sulfur is present as sulfate that must undergo an elaborate eight-electron transfer to hydrogen sulfide ( H2S ). This reduction reaction is found in plants and microorganisms but not in the animal kingdom.

Cysteine synthesis is accomplished by sulfhydryl transfer to serine.


In some bacteria, hydrogene sulfide H2S a condenses directly with serine via a PLP-dependent enzyme catalyzed reaction (Figure a, above)

In many bacteria, the synthesis of cysteine from serine relies upon a PLP-dependent beta-substitution  step.  In this pathway, serine is first acetylated by acetyl-CoA (an acyl transfer reaction). 


The acetylated serine forms an imine linkage with PLP, then undergoes an elimination (steps 1-2 below) in which the acetyl group is expelled (acetyl is, of course,  a much weaker base / better leaving group than a hydroxide - thus the function of the initial serine acetylation step).



A sulfhydryl ion (SH-) then attacks in a Michael addition (steps 3-4), with the intermediate stabilized again by the electron-sink property of PLP.  Finally, the cysteine product is released from PLP (step 5) via an imine exchange reaction with an active site lysine.

In most microorganisms and green plants, the sulfhydrylation reaction requires an activated form of serine, O-acetylserine (Figure b below).



O-acetylserine is made by serine acetyltransferase, with the transfer of an acetyl group from acetyl-CoA to the OOH of Ser. This enzyme is inhibited by Cys. O-Acetylserine then undergoes sulfhydrylation by H2S with elimination of acetate; the enzyme is O-acetylserine sulfhydrylase.

Acetyl Coenzyme A

The structure of the important activated carrier molecule acetyl CoA. 
A ball-and-stick model is shown above the structure. The sulfur atom (yellow) forms a thioester bond to acetate. Because this is a high-energy linkage, releasing a large amount of free energy when it is hydrolyzed, the acetate
molecule can be readily transferred to other molecules. 3

Prebiotic synthesis os Cysteine
Even though the presence of sulfur-containing compounds in proteins had been known since the mid-19th century, it was only with the laborious work of John Mueller in the early 1920s that one of the components was identified as an amino acid other than cysteine. Methionine is the immediate precursor of S-adenosylmethionine (SAM), the major methyl-group donor in transmethylation reactions in contemporary biochemistry. 5
The serine family includes three amino acids: serine, glycine, and cysteine. Cysteine synthesis  funnels sulfur into the biochemical world and supplies the cysteine needed for biosynthesis. 6


a  Hydrogen sulfide is the chemical compound with the formula H2S. It is a colorless gas with the characteristic foul odor of rotten eggs. It is very poisonous, corrosive, and flammable
https://en.wikipedia.org/wiki/Hydrogen_sulfide

b An acid–base reaction is a chemical reaction that occurs between an acid and a base. Several theoretical frameworks provide alternative conceptions of the reaction mechanisms and their application in solving related problems; these are called the acid–base theories. An acid dissociation constantKa, (also known as acidity constant, or acid-ionization constant) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid–base reactions 
https://en.wikipedia.org/wiki/Acid_dissociation_constant



1. Biochemistry, 6th edition, Garrett, page 906
2. Pyridoxal phosphate - an electron sink cofactor
3. Molecular biology of the Cell, 6th Ed. page 69
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355186/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094541/
6. Origins of Life on the Earth and in the Cosmos SECOND EDITION, page 287 
7. https://en.wikipedia.org/wiki/Serine_O-acetyltransferase
8. https://www.sciencedirect.com/science/article/pii/S0003986104004552
9. http://worldofbiochemistry.blogspot.com.br/search/label/Aminoacid%20metabolism
10.  Sulfur Assimilation and Abiotic Stress in Plants,  page 97 
11. https://en.wikipedia.org/wiki/Cysteine#Biosynthesis
12. Fundamentals of biochemistry, 5th ed. page 752



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17 Lysine on Sat May 05, 2018 4:38 am

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Lysine, Methionine, and Threonine Are Synthesized from Aspartate
In bacteria, aspartate is the common precursor of lysine, methionine, and threonine


The biosynthesis of the aspartate family of amino acids: lysine, methionine, and threonine.
The pathway enzymes shown are (1) aspartokinase, (2) β-aspartate semialdehyde dehydrogenase, (3) homoserine dehydrogenase, and (4) methionine synthase (a coenzyme B12–dependent enzyme).

The biosyntheses of these essential amino acids all begin with the aspartokinase-catalyzed phosphorylation of aspartate to yield aspartyl-b- phosphate. The control of metabolic pathways commonly occurs at the first committed step of the pathway. One might , therefore,expect lysine, methionine, and threonine biosynthesis to be controlled as a group. Each of these pathways is, in fact, independently controlled. E. coli has three isozymes a of aspartokinase that respond diff erently to the three amino acids in terms both of feedback inhibition of enzyme activity and repression of enzyme synthesis. In
addition, the pathway direction is controlled by feedback inhibition at the branch
points by the amino acid products of the branches.

a Isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. 1


1. https://en.wikipedia.org/wiki/Isozyme



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18 Arginine on Sun Jul 22, 2018 12:53 pm

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Arginine

Biosynthesis
Arginine is synthesized from citrulline in arginine and proline metabolism by the sequential action of the cytosolic enzymes argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL). In terms of energy, this is costly, as the synthesis of each molecule of argininosuccinate requires hydrolysis of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), i.e., two ATP equivalents. In essence, taking an excess of arginine gives more energy by saving ATPs that can be used elsewhere.

Citrulline can be derived from multiple sources:

from arginine via nitric oxide synthase (NOS)
from ornithine via catabolism of proline or glutamine/glutamate
from asymmetric dimethylarginine (ADMA) via DDAH
The pathways linking arginine, glutamine, and proline are bidirectional. Thus, the net utilization or production of these amino acids is highly dependent on cell type and developmental stage.
On a whole-body basis, synthesis of arginine occurs principally via the intestinal–renal axis, wherein epithelial cells of the small intestine, which produce citrulline primarily from glutamine and glutamate, collaborate with the proximal tubule cells of the kidney, which extract citrulline from the circulation and convert it to arginine, which is returned to the circulation. As a consequence, impairment of small bowel or renal function can reduce endogenous arginine synthesis, thereby increasing the dietary requirement.
Synthesis of arginine from citrulline also occurs at a low level in many other cells, and cellular capacity for arginine synthesis can be markedly increased under circumstances that also induce iNOS. Thus, citrulline, a coproduct of the NOS-catalyzed reaction, can be recycled to arginine in a pathway known as the citrulline-NO or arginine-citrulline pathway. This is demonstrated by the fact that, in many cell types, citrulline can substitute for arginine to some degree in supporting NO synthesis. However, recycling is not quantitative because citrulline accumulates along with nitrate and nitrite, the stable end-products of NO, in NO-producing cells.[6]






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19 Histidine on Mon Jul 23, 2018 7:00 pm

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Histidine Biosynthesis Includes an Intermediate in Nucleotide Biosynthesis.
Five of histidine’s six C atoms are derived from 5-phosphoribosyl-



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20 Aspartate ( Aspartic acid ) on Fri Aug 03, 2018 8:55 am

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Aspartate

Aspartate is formed from the citric acid cycle intermediate oxaloacetate by transfer of an amino group from glutamate via a PLP-dependent aminotransferase reaction (Figure below).



Like glutamate synthesis from a-ketoglutarate, aspartate synthesis is a drain on the citric acid cycle. The Asp amino group serves as the N donor in the conversion of citrulline to arginine.  This ONH2 is also the source of one of the N atoms of the purine ring system during nucleotide biosynthesis, as well as the C-6-amino-group of the major purine adenine. The entire aspartate molecule is also used in the biosynthesis of pyrimidine nucleotides.







1


Aspartate and alanine can be made from the addition of an amino group to oxaloacetate and pyruvate, respectively.

Oxaloacetate




Aspartate synthesis under prebiotic conditions

Mineral Concentration of Amino Acids on the 1 Early Earth: Aspartate 2
Conclusions: We have examined the sorption of aspartate into layered double hydroxides. Our studies have shown that, contrary to previous studies (Aisawa et al., 2004), it is possible to anion-exchange chloride-LDHs with amino acids at up to 100% of the anion exchange capacity by using alkaline pH conditions, giving an interlayer amino acid concentration of 7.93 mol/L starting from a very dilute solution (0.020 mol/L). Under geochemical conditions, it may be postulated that other anions may compete with the amino acids, though even at pH where considerable OH- species are present, full exchange occurs. The strong affinity of LDH toward carbonate anions may restrict its anionic exchange capacity and the overall interlayer structure of the hybrid MgRAl-Asp system may be altered concomitantly.

1. Biochemistry, 5th edition, Styer, page 720
2. http://sci-hub.tw/https://www.sciencedirect.com/science/article/pii/S0016703715007206



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21 Glutamate ( Glutamic Acid ) on Fri Aug 03, 2018 9:08 am

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ki



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Histidine

Histidine (abbreviated as His or H) is an α-amino acid with an imidazole functional group. It is one of the 23 proteinogenic amino acids. Its codons are CAU and CAC.Histidine is an essential amino acid in humans and other mammals. It was initially thought that it was only essential for infants, but longer-term studies established that it is also essential for adult humans.

Histidine is formed by several complex and distinct biochemical reactions catalysed by eight enzymes. Proteins involved in steps 4 and 6 of the histidine biosynthesis pathway are contained in one family. These enzymes are called His6 and His7 in eukaryotes and HisA and HisF in prokaryotes. HisA is a phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (EC:5.3.1.16), involved in the fourth step of histidine biosynthesis. The bacterial HisF protein is a cyclase which catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate during the sixth step of histidine biosynthesis. The yeast His7 protein is a bifunctional protein which catalyzes an amido-transferase reaction that generates imidazole-glycerol phosphate and 5-aminoimidazol-4-carboxamide. The latter is the ribonucleotide used for purine biosynthesis. The enzyme also catalyzes the cyclization reaction that produces D-erythro-imidazole glycerol phosphate, and is involved in the fifth and sixth steps in histidine biosynthesis. 1

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Nonessential Amino Acids Are Synthesized from Common Metabolites
All the nonessential amino acids except tyrosine are synthesized by simple pathways leading from one of four common metabolic intermediates: pyruvate, oxaloacetate, α-ketoglutarate, and 3-phosphoglycerate. Tyrosine, which is really misclassified as being non-essential, is synthesized by the one-step hydroxylation of the essential amino acid phenylalanine. 

Pyruvate, oxaloacetate, and α-ketoglutarate are the α-keto acids (the so-called carbon skeletons) that correspond to alanine, aspartate, and glutamate, respectively. Indeed, the synthesis of each of the amino acids is a one-step transamination reaction ( Reactions 1–3). The ultimate source of the α-amino group in these transamination reactions is glutamate, which is synthesized in microorganisms, plants, and lower eukaryotes by glutamate synthase , an enzyme that is absent in vertebrates. Asparagine and glutamine are, respectively, synthesized from aspartate and glutamate by ATP-dependent amidation.


The syntheses of alanine, aspartate, glutamate, asparagine, and glutamine. 
These reactions involve, respectively, transamination of (1) pyruvate, (2) oxaloacetate, and (3) α-ketoglutarate, and amidation of (4) aspartate and (5) glutamate.

Alanine



So, what about the results of Miller’s experiment?  He obtained a “soup” that contained around 9 amino acids, 2% of the simplest, glycine and alanine, and traces of 7 others. 1

Cytosolic glutamic-pyruvate transaminase (alanine aminotransferase) (GPT) catalyzes the reversible reaction of pyruvate and glutamate to form alanine and 2-oxoglutarate (alpha-ketoglutarate) 6

The pyruvate family of amino acids includes alanine (Ala), valine (Val), and leucine (Leu). 

Glycolysis is the sequence of reactions that metabolizes one molecule of glucose to two molecules of pyruvate with the concomitant net production of two molecules of ATP. This process is anaerobic (i.e., it does not require O2 )

Transamination of pyruvate, with glutamate as amino donor, gives alanine. Because these transamination reactions are readily reversible, alanine degradation occurs via the reverse route, with a-ketoglutarate serving as amino acceptor. Transamination a of pyruvate to alanine is a reaction found in virtually all organisms.



Aspartate, alanine, and glutamate are formed by the addition of an amino group to an alpha-ketoacid
Three a-ketoacids— a-ketoglutarate, oxaloacetate, and pyruvate—can be converted into amino acids in one step through the addition of an amino group. We have seen that a -ketoglutarate can be converted into glutamate by reductive amination

http://en.wikipedia.org/wiki/Alanine#Biosynthesis

Biosynthesis
Alanine can be manufactured in the body from pyruvate and branched chain amino acids such as valine, leucine, and isoleucine.
Alanine is most commonly produced by reductive amination of pyruvate. Because transamination reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. It also arises together with lactate and generates glucose from protein via the alanine cycle.

http://biocyc.org/ECOLI/NEW-IMAGE?type=PATHWAY&object=PWY0-1061

L-alanine is an essential component of protein and peptidoglycan. The latter also contains about three molecules of D-alanine for every L-alanine. Only about 10 percent of the total alanine synthesized flows into peptidoglycan.

At least three pathways (alanine biosynthesis I, alanine biosynthesis II, and alanine biosynthesis III) contribute to the synthesis of alanine. Alanine biosynthesis I is established only by existence of the relevant enzymes. Its contribution to alanine synthesis remains speculative because alanine auxotrophs have not yet been isolated. Because alanine but not valine represses AvtA, its primary purpose is probably synthesis of L-alanine [Falkinham79, Whalen82]. Existence of the Alanine biosyntheis II pathways rests on the evidence that glutamate-pyruvate aminotransferase acitivity is found in crude cell extracts; the enzymes has not been purified nor have mutant alleles of its designated encoding gene (alaB) been isolated [Falkinham79, Raunio73a]. The conversion can also be mediated as a side reaction of alanine racemase [Kurokawa98]. The alanine biosyntheis III pathway, mediated by cysteine desulfurase activity, which is required to donate sulfane sulfur for the synthesis of Fe-S clusters, thiamine, thionucleosides in tRNAs, biotin, lipoic acid, and molybdopterin [Mihara02a], probably contributes only a minor amount of the cell's alanine requirement, as judged by the cell's total requirement for sulfane sulfur.

A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system 3

So, what about the results of Miller’s experiment?  He obtained a “soup” that contained around 9 amino acids, 2% of the simplest, glycine and alanine, and traces of 7 others. 1

Biosynthesis 2
Alanine can be manufactured in the body from pyruvate and branched chain amino acids such as valine, leucine, and isoleucine. Alanine is most commonly produced by reductive amination of pyruvate. Because transamination reactions are readily reversible and pyruvate pervasive, alanine can be easily formed and thus has close links to metabolic pathways such as glycolysis, gluconeogenesis, and the citric acid cycle. It also arises together with lactate and generates glucose from protein via the alanine cycle.

http://biocyc.org/ECOLI/NEW-IMAGE?type=PATHWAY&object=PWY0-1061

L-alanine is an essential component of protein and peptidoglycan. The latter also contains about three molecules of D-alanine for every L-alanine. Only about 10 percent of the total alanine synthesized flows into peptidoglycan.

At least three pathways (alanine biosynthesis I, alanine biosynthesis II, and alanine biosynthesis III) contribute to the synthesis of alanine. Alanine biosynthesis I is established only by existence of the relevant enzymes. Its contribution to alanine synthesis remains speculative because alanine auxotrophs have not yet been isolated. Because alanine but not valine represses AvtA, its primary purpose is probably synthesis of L-alanine . Existence of the Alanine biosyntheis II pathways rests on the evidence that glutamate-pyruvate aminotransferase acitivity is found in crude cell extracts; the enzymes has not been purified nor have mutant alleles of its designated encoding gene (alaB) been isolated . The conversion can also be mediated as a side reaction of alanine racemase [Kurokawa98]. The alanine biosyntheis III pathway, mediated by cysteine desulfurase activity, which is required to donate sulfane sulfur for the synthesis of Fe-S clusters, thiamine, thionucleosides in tRNAs, biotin, lipoic acid, and molybdopterin [Mihara02a], probably contributes only a minor amount of the cell's alanine requirement, as judged by the cell's total requirement for sulfane sulfur.






a Transamination, a chemical reaction that transfers an amino group to a ketoacid to form new amino acids. This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential amino acids to nonessential amino acids (amino acids that can be synthesized de novo by the organism). Transamination in biochemistry is accomplished by enzymes called transaminases or aminotransferases. α-ketoglutarate acts as the predominant amino-group acceptor and produces glutamate as the new amino acid. 4

b Auxotrophy (Ancient Greek: "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth 5



1. http://www.truthinscience.org.uk/tis2/index.php/evidence-for-evolution-mainmenu-65/51-the-miller-urey-experiment.html
2. http://en.wikipedia.org/wiki/Alanine#Biosynthesis
3. http://www.drugbank.ca/drugs/DB00160
4. https://en.wikipedia.org/wiki/Transamination
5. https://en.wikipedia.org/wiki/Auxotrophy
6. http://reactome.org/content/detail/R-HSA-70524

further readings:

http://www.uncommondescent.com/intelligent-design/have-glycine-but-no-life/
http://www.evolutionnews.org/2014/06/squeezing_the_l087261.html

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Amino acids are the fundamental building blocks of proteins, which are the main catalysts that support life. How amino acids were produced under early prebiotic conditions is an essential question to address in order to reveal the possible origin of life. There are numerous investigations about the origin of amino acids in the early earth. For instance, over 80 natural and non-natural amino acids have been detected in the carbonaceous chondrites (meteorites), which implies that amino acids in the terrestrial biosphere could originate from elsewhere in the solar system 1

Eight proteinogenic amino acids were abiotically synthesized under hydrothermal conditions, which ( supposedly ) supports the hypothesis that amino acids first appeared in submarine hydrothermal systems.


1. https://www.nature.com/articles/srep06769




Nitrogen acquisition and amino acid metabolism

Nitrogen is an essential nutrient for all cells. Amino acids provide nitrogen for the synthesis of other nitrogen-containing biomolecules. Excess amino acids in the diet can be converted into a-keto acids and used for energy production. Amino acids and nucleotides, as well as their polymeric forms (proteins and nucleic acids), are nitrogen-containing molecules upon which cell structure and function rely. How do these various organic forms of nitrogen arise? As we look at these compounds, an obvious feature is that nitrogen atoms are typically bound to carbon and/or hydrogen atoms. That is, the nitrogen atom is in a reduced state. On the other hand, the prevalent forms of nitrogen in the environment are inorganic and oxidized; N2 (dinitrogen gas) and NO3- (nitrate ions) being the most abundant species. The two principal routes for nitrogen acquisition from the inanimate environment, nitrate assimilation and nitrogen fixation, lead to formation of ammonium ions (NH4-). Reactions that incorporate NH4+ into organic linkage (the reactions of ammonium assimilation) follow. Among these, glutamine synthetase merits particular attention because it conveys several important lessons in metabolic regulation. This chapter presents the pathways of amino acid biosynthesis and degradation; those involving the sulfur-containing amino acids provide an opportunity to introduce aspects of sulfur metabolism.

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Cysteine biosynthesis

In animals, biosynthesis begins with the amino acid serine. The sulfur is derived from methionine, which is converted to homocysteine through the intermediate S-adenosylmethionine. Cystathionine beta-synthase then combines homocysteine and serine to form the asymmetrical thioether cystathionine. The enzyme cystathionine gamma-lyase converts the cystathionine into cysteine and alpha-ketobutyrate. In plants and bacteria, cysteine biosynthesis also starts from serine, which is converted to O-acetylserine by the enzyme serine transacetylase. The enzyme O-acetylserine (thiol)-lyase, using sulfide sources, converts this ester into cysteine, releasing acetate. 11 

Cysteine is hydrophobic, and unique among the 20 amino acids in that it has a thiol group that can form a disulfide bond with another cysteine through the oxidation of the two thiol groups


Disulfide-bonded cysteine residues. 
The disulfide bond forms when the two thiol groups are oxidized. An important amino acid side-chain reaction is the formation of disulfide bonds via reaction between two cysteines. In proteins, cysteine residues form disulfide linkages that stabilize protein structure






Cysteine biosynthesis
Serine, Cysteine, and Glycine Are Derived from 3-Phosphoglycerate. In animals, cysteine is synthesized from serine and homocysteine, a breakdown product of methionine. Since cysteine’s sulfhydryl group is derived from the essential amino acid methionine, cysteine can be considered to be an essential amino acid. 12


Cysteine synthesis: Reactions 5 and 6

Cysteine biosynthesis is the metabolic link between sulfur assimilation and the myriad of sulfur-containing molecules in the cell. For example, this pathway provides essential metabolites for production of glutathione, a key regulatory agent of intracellular redox environment during abiotic and biotic stresses. 

10


9



The serine family includes three amino acids: serine, glycine, and cysteine (see Figure below). 6



Cysteine synthesis funnels sulfur into the biochemical world and supplies the cysteine needed for biosynthesis. 
The biosynthesis of L-cysteine entails the sulfhydryl transfer to an activated form of serine. In the first step an acetyl group is transferred from acetyl-coenzyme A (acetyl-CoA) to serine to yield O-acetylserine .

An acetyl group is transferred from acetyl-coenzyme A (acetyl-CoA) to serine to yield O-acetylserine. The reaction is catalyzed by Serine O-acetyltransferase. in a second step, cysteine is catalyzed by a second enzyme,  Cysteine synthase 



The reaction is catalyzed by Serine O-acetyltransferase. 



The N-terminal domain of the protein Serine acetyltransferase helps catalyze acetyl transfer. This particular enzyme catalyzes serine into cysteine. Of particular interest to scientists, is the ability to harness the natural ability of the enzyme, Serine acetyltransferase, to create nutritionally essential amino acids 7 and 8

The formation of cysteine itself is catalyzed by O-acetylserine sulfhydrylase ( Cysteine synthase ) 


Ribbon representation of the structure of OASS-A. ( O-acetylserine sulfhydrylase. ) 
Left, the dimer of OASS-A with PLP in space-filling representation. A molecular 2-fold axis runs from the lower left to the upper right of the molecule. Right, a monomer of OASS-A is shown. The two-domain nature of the structure is shown with the central, twisted -sheet in both domains surrounded by helices. The entry to the active site is on the left of the monomer. 

In the Archean world before the advent of atmospheric oxygen, most sulfur was probably present in the reduced state amenable to direct incorporation into cysteine. Currently, most sulfur is present as sulfate that must undergo an elaborate eight-electron transfer to hydrogen sulfide ( H2S ). This reduction reaction is found in plants and microorganisms but not in the animal kingdom.

Cysteine synthesis is accomplished by sulfhydryl transfer to serine.


In some bacteria, hydrogene sulfide H2S a condenses directly with serine via a PLP-dependent enzyme catalyzed reaction (Figure a, above)

In many bacteria, the synthesis of cysteine from serine relies upon a PLP-dependent beta-substitution  step.  In this pathway, serine is first acetylated by acetyl-CoA (an acyl transfer reaction). 


The acetylated serine forms an imine linkage with PLP, then undergoes an elimination (steps 1-2 below) in which the acetyl group is expelled (acetyl is, of course,  a much weaker base / better leaving group than a hydroxide - thus the function of the initial serine acetylation step).



A sulfhydryl ion (SH-) then attacks in a Michael addition (steps 3-4), with the intermediate stabilized again by the electron-sink property of PLP.  Finally, the cysteine product is released from PLP (step 5) via an imine exchange reaction with an active site lysine.

In most microorganisms and green plants, the sulfhydrylation reaction requires an activated form of serine, O-acetylserine (Figure b below).



O-acetylserine is made by serine acetyltransferase, with the transfer of an acetyl group from acetyl-CoA to the OOH of Ser. This enzyme is inhibited by Cys. O-Acetylserine then undergoes sulfhydrylation by H2S with elimination of acetate; the enzyme is O-acetylserine sulfhydrylase.

Acetyl Coenzyme A

The structure of the important activated carrier molecule acetyl CoA. 
A ball-and-stick model is shown above the structure. The sulfur atom (yellow) forms a thioester bond to acetate. Because this is a high-energy linkage, releasing a large amount of free energy when it is hydrolyzed, the acetate
molecule can be readily transferred to other molecules. 3

Prebiotic synthesis os Cysteine
Even though the presence of sulfur-containing compounds in proteins had been known since the mid-19th century, it was only with the laborious work of John Mueller in the early 1920s that one of the components was identified as an amino acid other than cysteine. Methionine is the immediate precursor of S-adenosylmethionine (SAM), the major methyl-group donor in transmethylation reactions in contemporary biochemistry. 5
The serine family includes three amino acids: serine, glycine, and cysteine. Cysteine synthesis  funnels sulfur into the biochemical world and supplies the cysteine needed for biosynthesis. 6

1. Biochemistry, 6th edition, Garrett, page 906
2. Pyridoxal phosphate - an electron sink cofactor
3. Molecular biology of the Cell, 6th Ed. page 69
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355186/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094541/
6. Origins of Life on the Earth and in the Cosmos SECOND EDITION, page 287 
7. https://en.wikipedia.org/wiki/Serine_O-acetyltransferase
8. https://www.sciencedirect.com/science/article/pii/S0003986104004552
9. http://worldofbiochemistry.blogspot.com.br/search/label/Aminoacid%20metabolism
10.  Sulfur Assimilation and Abiotic Stress in Plants,  page 97 
11. https://en.wikipedia.org/wiki/Cysteine#Biosynthesis
12. Fundamentals of biochemistry, 5th ed. page 752


a  Hydrogen sulfide is the chemical compound with the formula H2S. It is a colorless gas with the characteristic foul odor of rotten eggs. It is very poisonous, corrosive, and flammable
https://en.wikipedia.org/wiki/Hydrogen_sulfide

b An acid–base reaction is a chemical reaction that occurs between an acid and a base. Several theoretical frameworks provide alternative conceptions of the reaction mechanisms and their application in solving related problems; these are called the acid–base theories. An acid dissociation constantKa, (also known as acidity constant, or acid-ionization constant) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid–base reactions 
https://en.wikipedia.org/wiki/Acid_dissociation_constant



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