As implied bythe root of the word (amine), the key atom in amino acid composition isnitrogen. The ultimate source of nitrogen for thebiosynthesis of amino acids is atmospheric nitrogen (N2), a nearlyinert gas. However, to be metabolically useful, atmospheric nitrogen must bereduced. This process, known as nitrogen fixation, occurs only in certain typesof bacteria. Even though nitrogen is one of the most prominent chemicalelements in living systems, N2 is almost unreactive (and verystable) because of its triple bond (N≡N). This bond is extremely difficult tobreak because the three chemical bonds need to be separated and bonded todifferent compounds. Nitrogenase is the only family of enzymes capable ofbreaking this bond (i.e., it carries out nitrogen fixation). These proteins use a collection of metal ionsas the electron carriers that are responsible for the reduction of N2to NH3. All organisms can then use this reduced nitrogen (NH3)to make amino acids. In humans, reduced nitrogen enters the physiologicalsystem in dietary sources containing amino acids. All organisms contain theenzymesglutamate dehydrogenase and glutamine synthetase, which convert ammonia toglutamate and glutamine, respectively. Amino and amide groups from these twocompounds 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 manyother amino acids as well as many biosynthetic products. Glutamine is also akey metabolite for ammonia storage. All aminoacids, with the exception of proline, have a primary amino group (NH2)and a carboxylic acid (COOH) group. They are distinguished from one anotherprimarily by , appendages to the central carbonatom.

Amino Acid Precursors and Biosynthesis Pathways


Plants and bacteria do not synthesize all amino acids, and some amino acids are synthesized by pathways that are unique to them.Eight of the twenty amino acids needed by mammals must be obtained through their diets.The result is a convention which divides amino acids into two categories: essential and non-essential (given a certain metabolism).Unlike other amino acids, essential amino acids cannot be synthesized by mammalian enzymes (Reeds 2000).Since nonessential amino acids can be synthesized by nearly all organisms, they are available to synthesize.The ability to synthesize essential amino acids likely evolved very early in evolution, since this dependence on other organisms for amino acids is common among all eukaryotes, not just mammals. A child at this stage of cognitive development is able to situate themselves within a larger temporal narrative that includes memories and anticipations, and to articulate these in language.Beginning rounds out the emergent process of the composition, culminating in the actual expression of the message.The cello interprets the text and the wind players recite it rhythmically in unison.As a result, the text the audience has been reading has a radically different function, serving as nothing more than confirmation of what they are hearing rather than providing an element of cross-modality.The result may surprise or seem logical depending on how familiar a listener has become with the evolution of the relationship between text and music in the previous Beginnings.

.Trpsynthesis pathways appear highly conserved, and enzymes required to synthesize tryptophan are widely distributed throughout all three realms of life.From chorismate, this pathway is one of three that produce aromatic amino acids (Figure 2, red pathway).Intriguingly, tyrosine and phenylalanine are also synthesized by Trp biosynthesis enzymes (Xie et al., 2003).This pathway's genes evolved once, and they did so more recently than other pathways that synthesize amino acids. .Trp is also the most biochemically expensive amino acid pathway, so it will be the most tightly regulated of the amino acid pathways.

To date, scientists have discovered six different biosyntheticpathways in different organisms that synthesize lysine. These pathways can begrouped into the diaminopimelic acid (DAP) and aminoadipic acid (AAA) pathways (Figure 2, dark blue). The DAP pathway synthesizes lysine (Lys)from aspartate and pyruvate. Most bacteria, some archaea, fungi, algae, andplants use the DAP pathways. On the other hand, the AAA pathways synthesize Lys from alpha-ketoglutarate and acetyl coenzyme A. Mostfungi, some algae, and some archaea use this route. Why do we observe thisdiversity, and why does it occur particularly for Lyssynthesis? Interestingly, the DAP pathways retain duplicated genes from thebiosynthesis of arginine, whereas the AAA pathways retain duplicated genes fromleucine biosynthesis (Figure 2), indicating thateach of the pathways experienced at least one duplication event duringevolution (Hernandez-Montes et al. 2008; Velasco et al. 2002). Faniand coworkers performed a comparative analysis of the synthesis enzymesequences and their phylogenetic distribution that suggested that the synthesisof leucine, lysine, and arginine were initially carried out with the same setof versatile enzymes. Over the course of time came a series of gene duplicationevents and enzyme specializations that gave rise to the unambiguous pathways weknow today. Which of the pathways appeared earlier is still a source of queryand debate.

To support this hypothesis, there is evidence from a fascinating archaea,Pyrococcus horikoshii. This organismcan synthesize leucine, lysine, and arginine, yet its genomecontains only genes for one pathway. Such a gap indicates that P. horikoshii has amechanism similar to the ancestral one: versatile enzymes. Biochemical experiments are needed to further supportthe idea that these enzymes can use multiple substrates and to rule out thepossibility that amino acid synthesis in this organism does not arise fromenzymes yet unidentified.

Selenocysteine (SeC) (Bock 2000) is a genetically encoded amino acid not present in allorganisms. Scientists have identified SeC in several archaeal, bacterial,and eukaryotic species (even mammals). When present, SeC is usually confined to active sites of proteins involved inreduction-oxidation (redox) reactions. It is highly reactive and has catalyticadvantages over cysteine, but this high reactivity is undermined by itspotential to cause cell damage if free in the cytoplasm. Hence, it is toodangerous, and no pool of free SeC is available. How, then, is this amino acidsynthesized for use in protein synthesis? The answer demonstrates theversatility of synthesis strategies deployed by organisms forced to cope withsingularities. The synthesis of SeC is carriedout directly on the tRNA substrate before being used in protein synthesis.First, SeC-specific tRNA (tRNAsec) is charged with serine viaseril-tRNA synthetase, which acts in a somehow promiscuous fashion, serilatingeither tRNAser or tRNAsec. Then, another enzyme modifiesSer to SeC by substituting the OH radical with SeH, using selenophosphate asthe selenium donor (Figure 2, pink pathway). This synthesis is a form of a trickto avoid the existence of a free pool of SeC while still maintaining a sourceof SeC-tRNAsec needed for protein synthesis. Strictly speaking, thismechanism is not an actual synthesis of amino acids, but rather a synthesis ofaminoacetylated-tRNAs. However, this technique involving tRNA directly is notexclusive to SeC, and similar mechanisms dependent on tRNA have been describedfor asparagine, glutamine, and cysteine. Owing to its appearance of SeC acrossall three domains of life, scientists wonder if it is an ancestral mechanismfor amino acid biosynthesis or simply a coincidence of selection pressures.

In 1945, Horowitz proposed the firstaccepted model for metabolic pathway evolution (Horowitz1945). Called theretrograde model, it states that after an enzyme consumes all its substrateavailable, another enzyme capable of producing the aforementioned substrate isrequired, so the last enzyme evolved to the preceding one by a gene duplicationand selection mechanism. In other words, enzymes evolve from others withsimilar substrate specificity, and the substrate of the last enzyme is theproduct of the preceding one. Also, the active site must bind both thesubstrate and the product. This model became very popular, but as more geneshave been sequenced and more phylogenetic analyses performed, this mechanism hasbecome less seemingly plausible and therefore unpopular. An alternative model,the patchwork assembly model, proposes that ancestralenzymes were generalists, so they could bind a number of substrates to carryout the same type of reaction. Gene duplication events followed by evolutionarydivergence would result in enzymes with high affinity and specificity for asubstrate. In other words, enzymes are recruited from others with the same typeof chemical reaction. Whole genome analysis of Escherichia coli supports the patchwork evolution model (Teichmann et al. 2001). Duplication of whole pathways does not occur very often;nevertheless, examples include tryptophan (to synthesize paraminobenzoate) andhistidine (to synthesize nucleotides) biosynthesis, as well as lysine, arginine,and leucine biosynthesis (see aforementioned example).

The first organic molecules found on Earth are amino acids.Aminoacids, which form the building blocks for proteins, are central to almost every biological process. They are also key precursors in many physiological processes.In addition to intermediary metabolism (the connection between carbohydrates and lipids), signal transduction, and neurotransmission are also involved.Amino acid evolution has seen significant advances in recent years, but many questions regarding amino acid synthesis remain.Which amino acids first appeared over evolutionary time?

Scientists now recognize twenty-twoamino acids as the building blocks of proteins: the twenty common ones and twomore, selenocysteine and pyrrolysine. Amino acids have several functions. Theirprimary function is to act as the monomer unit in protein synthesis. They canalso be used as substrates for biosynthetic reactions; the nucleotide bases anda number of hormones and neurotransmitters are derived from amino acids. Aminoacids can be synthesized from glycolytic or Krebs cycle intermediates. Theessential amino acids, those that are needed in the diet, require more steps tobe synthesized. Some amino acids need to be synthesized when charged onto theircorresponding tRNAs. We have discussed only two biosynthetic routes: the Trppathway, which appears to have evolved only once, and the Lyspathway, which seems to have evolved independently in different lineages.Prevailing evidence suggests that metabolic pathways themselves seem to beevolving following the patchwork assembly model, which proposes that pathwaysoriginated through the recruitment of generalist enzymes that could react witha wide range of substrates. The study of the evolution of amino acid metabolismhas helped us understand the evolution of metabolism in general.

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