Amino acid explained

Amino acids are organic compounds that contain both amino and carboxylic acid functional groups.[1] Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins.[2] Only these 22 appear in the genetic code of life.[3] [4]

Amino acids can be classified according to the locations of the core structural functional groups (alpha- (α-), beta- (β-), gamma- (γ-) amino acids, etc.); other categories relate to polarity, ionization, and side-chain group type (aliphatic, acyclic, aromatic, polar, etc.). In the form of proteins, amino-acid residues form the second-largest component (water being the largest) of human muscles and other tissues.[5] Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life on Earth and its emergence.[6]

Amino acids are formally named by the IUPAC-IUBMB Joint Commission on Biochemical Nomenclature in terms of the fictitious "neutral" structure shown in the illustration. For example, the systematic name of alanine is 2-aminopropanoic acid, based on the formula . The Commission justified this approach as follows:[7]

The systematic names and formulas given refer to hypothetical forms in which amino groups are unprotonated and carboxyl groups are undissociated. This convention is useful to avoid various nomenclatural problems but should not be taken to imply that these structures represent an appreciable fraction of the amino-acid molecules.

History

The first few amino acids were discovered in the early 1800s.[8] [9] In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound from asparagus that was subsequently named asparagine, the first amino acid to be discovered.[10] [11] Cystine was discovered in 1810,[12] although its monomer, cysteine, remained undiscovered until 1884.[13] [11] Glycine and leucine were discovered in 1820.[14] The last of the 20 common amino acids to be discovered was threonine in 1935 by William Cumming Rose, who also determined the essential amino acids and established the minimum daily requirements of all amino acids for optimal growth.[15] [16]

The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it.[17] The first use of the term "amino acid" in the English language dates from 1898,[18] while the German term, German: Aminosäure, was used earlier.[19] Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister independently proposed that proteins are formed from many amino acids, whereby bonds are formed between the amino group of one amino acid with the carboxyl group of another, resulting in a linear structure that Fischer termed "peptide".[20]

Structure

α-amino acids

2-, alpha-, or α-amino acids[21] have the generic formula in most cases, where R is an organic substituent known as a "side chain".[22]

Of the many hundreds of described amino acids, 22 are proteinogenic ("protein-building").[23] [24] [25] It is these 22 compounds that combine to give a vast array of peptides and proteins assembled by ribosomes.[26] Non-proteinogenic amino acids may arise through nonribosomal peptide synthesis.[27] Modified amino acids, by contrast, typically result from post-translational modification.[28]

β- and γ-amino acids

Amino acids with the structure, such as β-alanine, a component of carnosine and a few other peptides, are β-amino acids. Ones with the structure are γ-amino acids, and so on, where X and Y are two substituents (one of which is normally H).

Chirality

The carbon atom next to the carboxyl group is called the α–carbon. In proteinogenic amino acids, it bears the amine and the R group or side chain specific to each amino acid, as well as a hydrogen atom. With the exception of glycine, for which the side chain is also a hydrogen atom, the α–carbon is stereogenic. All chiral proteogenic amino acids have the L configuration. They are "left-handed" enantiomers, which refers to the stereoisomers of the alpha carbon.

A few D-amino acids ("right-handed") have been found in nature, e.g., in bacterial envelopes, as a neuromodulator (D-serine), and in some antibiotics.[29] [30] Rarely, D-amino acid residues are found in proteins, and are converted from the L-amino acid as a post-translational modification.[31]

Side chains

Polar charged

Five amino acids possess a charge at neutral pH. Often these side chains appear at the surfaces on proteins to enable their solubility in water, and side chains with opposite charges form important electrostatic contacts called salt bridges that maintain structures within a single protein or between interfacing proteins.[32] Many proteins bind metal into their structures specifically, and these interactions are commonly mediated by charged side chains such as aspartate, glutamate and histidine. Under certain conditions, each ion-forming group can be charged, forming double salts.[33]

The two negatively charged amino acids at neutral pH are aspartate (Asp, D) and glutamate (Glu, E). The anionic carboxylate groups behave as Brønsted bases in most circumstances. Enzymes in very low pH environments, like the aspartic protease pepsin in mammalian stomachs, may have catalytic aspartate or glutamate residues that act as Brønsted acids.[34] [35]

There are three amino acids with side chains that are cations at neutral pH: arginine (Arg, R), lysine (Lys, K) and histidine (His, H). Arginine has a charged guanidino group and lysine a charged alkyl amino group, and are fully protonated at pH 7. Histidine's imidazole group has a pKa of 6.0, and is only around 10% protonated at neutral pH. Because histidine is easily found in its basic and conjugate acid forms it often participates in catalytic proton transfers in enzyme reactions.

Polar uncharged

The polar, uncharged amino acids serine (Ser, S), threonine (Thr, T), asparagine (Asn, N) and glutamine (Gln, Q) readily form hydrogen bonds with water and other amino acids. They do not ionize in normal conditions, a prominent exception being the catalytic serine in serine proteases. This is an example of severe perturbation, and is not characteristic of serine residues in general. Threonine has two chiral centers, not only the L (2S) chiral center at the α-carbon shared by all amino acids apart from achiral glycine, but also (3R) at the β-carbon. The full stereochemical specification is (2S,3R)-L-threonine.[36]

Because of the presence of phenolic hydroxyl group with a pKa = ~10, tyrosine is best classified as a neutral polar amino acid, but with amphipathic character that makes it less polar than classical small polar amino acid residues.[37]

Hydrophobic

Nonpolar amino acid interactions are the primary driving force behind the processes that fold proteins into their functional three dimensional structures. None of these amino acids' side chains ionize easily, and therefore do not have pKas.

Classification outliers

Several side chains are not described well by the charged, polar and hydrophobic categories. Glycine (Gly, G) could be considered a polar amino acid since its small size means that its solubility is largely determined by the amino and carboxylate groups. However, the lack of any side chain provides glycine with a unique flexibility among amino acids with large ramifications to protein folding. Cysteine (Cys, C) can also form hydrogen bonds readily, which would place it in the polar amino acid category, though it can often be found in protein structures forming covalent bonds, called disulphide bonds, with other cysteines. These bonds influence the folding and stability of proteins, and are essential in the formation of antibodies. Proline (Pro, P) has an alkyl side chain and could be considered hydrophobic, but because the side chain joins back onto the alpha amino group it becomes particularly inflexible when incorporated into proteins. Similar to glycine this influences protein structure in a way unique among amino acids. Selenocysteine (Sec, U) is a rare amino acid not directly encoded by DNA, but is incorporated into proteins via the ribosome. Selenocysteine has a lower redox potential compared to the similar cysteine, and participates in several unique enzymatic reactions.[38] Pyrrolysine (Pyl, O) is another amino acid not encoded in DNA, but synthesized into protein by ribosomes.[39] It is found in archaeal species where it participates in the catalytic activity of several methyltransferases.[40]

Physicochemical properties

The 20 canonical amino acids can be classified according to their properties. Important factors are charge, hydrophilicity or hydrophobicity, size, and functional groups. These properties influence protein structure and protein–protein interactions. The water-soluble proteins tend to have their hydrophobic residues (Leu, Ile, Val, Phe, and Trp) buried in the middle of the protein, whereas hydrophilic side chains are exposed to the aqueous solvent. (In biochemistry, a residue refers to a specific monomer within the polymeric chain of a polysaccharide, protein or nucleic acid.) The integral membrane proteins tend to have outer rings of exposed hydrophobic amino acids that anchor them in the lipid bilayer. Some peripheral membrane proteins have a patch of hydrophobic amino acids on their surface that sticks to the membrane. In a similar fashion, proteins that have to bind to positively charged molecules have surfaces rich in negatively charged amino acids such as glutamate and aspartate, while proteins binding to negatively charged molecules have surfaces rich in positively charged amino acids like lysine and arginine. For example, lysine and arginine are present in large amounts in the low-complexity regions of nucleic-acid binding proteins.[41] There are various hydrophobicity scales of amino acid residues.[42]

Some amino acids have special properties. Cysteine can form covalent disulfide bonds to other cysteine residues. Proline forms a cycle to the polypeptide backbone, and glycine is more flexible than other amino acids.[43]

Glycine and proline are strongly present within low complexity regions of both eukaryotic and prokaryotic proteins, whereas the opposite is the case with cysteine, phenylalanine, tryptophan, methionine, valine, leucine, isoleucine, which are highly reactive, or complex, or hydrophobic.[44] [45]

Many proteins undergo a range of posttranslational modifications, whereby additional chemical groups are attached to the amino acid residue side chains sometimes producing lipoproteins (that are hydrophobic),[46] or glycoproteins (that are hydrophilic)[47] allowing the protein to attach temporarily to a membrane. For example, a signaling protein can attach and then detach from a cell membrane, because it contains cysteine residues that can have the fatty acid palmitic acid added to them and subsequently removed.[48]

Acid-base behavior

Zwitterions

See main article: Zwitterion.

The common natural forms of amino acids have a zwitterionic structure, with (in the case of proline) and functional groups attached to the same C atom, and are thus α-amino acids, and are the only ones found in proteins during translation in the ribosome.In aqueous solution at pH close to neutrality, amino acids are energetically favored in their zwitterionic form, with a deprotonated group and a protonated group, because the high dielectric constant of water and its hydrogen-bonding network effectively stabilize separated charges. Thus, the overall structure is, and the so-called "neutral forms" are not present to any measurable degree at physiological pH.[49] A zwitterion has a net charge of zero, but because it contains both positively and negatively charged sites, it is misleading to describe it as "uncharged."[50]

In contrast, in low-dielectric hydrophobic environments such as organic solvents or cell membrane interiors, charge separation is poorly stabilized and proton transfer tends to yield a neutral form, while in the gas phase, where there is essentially no dielectric screening or solvation, spectroscopic and computational studies show that the lowest-energy structures of most amino acids are also neutral unless specific intramolecular interactions or stepwise hydration provide sufficient stabilization of the zwitterion.[51]

In strongly acidic conditions (pH below 3), the carboxylate group becomes protonated and the structure becomes an ammonio carboxylic acid, . This is relevant for enzymes like pepsin that are active in acidic environments such as the mammalian stomach and lysosomes, but does not significantly apply to intracellular enzymes.[52] In highly basic conditions (pH greater than 10, not normally seen in physiological conditions), the ammonio group is deprotonated to give .[53]

Although various definitions of acids and bases are used in chemistry, the only one that is useful for chemistry in aqueous solution is that of Brønsted:[54] an acid is a species that can donate a proton to another species, and a base is one that can accept a proton. This criterion is used to label the groups in the above illustration. The carboxylate side chains of aspartate and glutamate residues are the principal Brønsted bases in proteins. Likewise, lysine, tyrosine and cysteine will typically act as a Brønsted acid. Histidine under these conditions can act both as a Brønsted acid and a base.[55]

Isoelectric point

For amino acids with uncharged side-chains the zwitterion predominates at pH values between the two pKa values, but coexists in equilibrium with small amounts of net negative and net positive ions. At the midpoint between the two pKa values, the trace amount of net negative and trace of net positive ions balance, so that average net charge of all forms present is zero.[56] This pH is known as the isoelectric point pI, so pI = (pKa1 + pKa2).

For amino acids with charged side chains, the pKa of the side chain is involved. Thus for aspartate or glutamate with negative side chains, the terminal amino group is essentially entirely in the charged form, but this positive charge needs to be balanced by the state with just one C-terminal carboxylate group is negatively charged. This occurs halfway between the two carboxylate pKa values: pI = (pKa1 + pKa(R)), where pKa(R) is the side chain pKa.[57]

Similar considerations apply to other amino acids with ionizable side-chains, including not only glutamate (similar to aspartate), but also cysteine, histidine, lysine, tyrosine and arginine with positive side chains.

Amino acids have zero mobility in electrophoresis at their isoelectric point, although this behaviour is more usually exploited for peptides and proteins than single amino acids.[58] Zwitterionic amino acids exhibit minimal solubility at their isoelectric point, and in some cases can be isolated from aqueous solution by adjusting the pH to the appropriate isoelectric value.[59]

Abbreviation and property tables

See main article: Proteinogenic amino acid.

Although one-letter symbols are included in the table, IUPAC–IUBMB recommend that "Use of the one-letter symbols should be restricted to the comparison of long sequences".[7]

The one-letter notation was chosen by IUPAC-IUB based on the following rules:[60]

Amino acid3- and 1-letter symbolsSide chainHydropathy
index[63] 		Molar absorptivity[64] Molecular massAbundance in proteins (%)[65] Standard genetic coding,
IUPAC notation
31ClassChemical polarity[66] Net charge
at pH 7.4		Wavelength,
λmax (nm)		Coefficient ε
(mM−1·cm−1)
AlanineAlaAAliphaticNonpolarNeutral1.889.0948.76GCN
ArginineArgRFixed cationBasic polarPositive−4.5174.2035.78MGR, CGY
AsparagineAsnNAmidePolarNeutral−3.5132.1193.93AAY
AspartateAspDAnionBrønsted baseNegative−3.5133.1045.49GAY
CysteineCysCThiolBrønsted acidNeutral2.52500.3121.1541.38UGY
GlutamineGlnQAmidePolarNeutral−3.5146.1463.9CAR
GlutamateGluEAnionBrønsted baseNegative−3.5147.1316.32GAR
GlycineGlyGAliphaticNonpolarNeutral−0.475.0677.03GGN
HistidineHisHCationicBrønsted acid and basePositive, 10%
Neutral, 90%		−3.22115.9155.1562.26CAY
IsoleucineIleIAliphaticNonpolarNeutral4.5131.1755.49AUH
LeucineLeuLAliphaticNonpolarNeutral3.8131.1759.68YUR, CUY
LysineLysKCationBrønsted acidPositive−3.9146.1895.19AAR
MethionineMetMThioetherNonpolarNeutral1.9149.2082.32AUG
PhenylalaninePheFAromaticNonpolarNeutral2.8257, 206, 1880.2, 9.3, 60.0165.1923.87UUY
ProlineProPCyclicNonpolarNeutral−1.6115.1325.02CCN
SerineSerSHydroxylicPolarNeutral−0.8105.0937.14UCN, AGY
ThreonineThrTHydroxylicPolarNeutral−0.7119.1195.53ACN
TryptophanTrpWAromaticNonpolarNeutral−0.9280, 2195.6, 47.0204.2281.25UGG
TyrosineTyrYAromaticBrønsted acidNeutral−1.3274, 222, 1931.4, 8.0, 48.0181.1912.91UAY
ValineValVAliphaticNonpolarNeutral4.2117.1486.73GUN

Two additional amino acids are in some species coded for by codons that are usually interpreted as stop codons:[67]

21st and 22nd amino acids3-letter1-letterMolecular mass
SelenocysteineSecU168.064
PyrrolysinePylO255.313

In addition to the specific amino acid codes, placeholders are used in cases where chemical or crystallographic analysis of a peptide or protein cannot conclusively determine the identity of a residue. They are also used to summarize conserved protein sequence motifs. The use of single letters to indicate sets of similar residues is similar to the use of abbreviation codes for degenerate bases.[68] [69]

Ambiguous amino acids3-letter1-letterAmino acids includedCodons included
Any / unknownXaa [70] XAllNNN
Asparagine or aspartateAsxBD, NRAY
Glutamine or glutamateGlxZE, QSAR
Leucine or isoleucineXleJI, LYTR, ATH, CTY
HydrophobicΦV, I, L, F, W, Y, MNTN, TAY, TGG
AromaticΩF, W, Y, HYWY, TTY, TGG
Aliphatic (non-aromatic)ΨV, I, L, MVTN, TTR
SmallπP, G, A, SBCN, RGY, GGR
HydrophilicζS, T, H, N, Q, E, D, K, RVAN, WCN, CGN, AGY
Positively-charged+K, R, HARR, CRY, CGR
Negatively-charged−D, EGAN

Unk[71] is sometimes used instead of Xaa, but is less standard.[72]

Ter or * (from termination) is used in notation for mutations in proteins when a stop codon occurs. It corresponds to no amino acid at all.[73]

In addition, many nonstandard amino acids have a specific code. For example, several peptide drugs, such as Bortezomib and MG132, are artificially synthesized and retain their protecting groups, which have specific codes. Bortezomib is Pyz–Phe–boroLeu, and MG132 is Z–Leu–Leu–Leu–al. To aid in the analysis of protein structure, photo-reactive amino acid analogs are available. These include photoleucine (pLeu) and photomethionine (pMet).[74]

Biological roles and occurrence

Proteinogenic

See also: Protein primary structure and Posttranslational modification.

Amino acids are the precursors to proteins.[26] They join by condensation reactions to form short polymer chains called peptides or longer chains called either polypeptides or proteins. These chains are linear and unbranched, with each amino acid residue within the chain attached to two neighboring amino acids. In nature, the process of making proteins encoded by RNA genetic material is called translation and involves the step-by-step addition of amino acids to a growing protein chain by a ribozyme that is called a ribosome.[75] The order in which the amino acids are added is read through the genetic code from an mRNA template, which is an RNA derived from one of the organism's genes.[76]

There are 22 amino acids that get naturally incorporated into polypeptides; these are called proteinogenic amino acids or natural amino acids. Of these, 20 are encoded by the universal genetic code. The remaining 2, selenocysteine and pyrrolysine, are incorporated into proteins by unique synthetic mechanisms. Selenocysteine is incorporated when the mRNA being translated includes a SECIS element, which causes the UGA codon to encode selenocysteine instead of a stop codon.[77] Pyrrolysine is used by some methanogenic archaea in enzymes that they use to produce methane. It is coded for with the codon UAG, which is normally a stop codon in other organisms.[78]

Several independent evolutionary studies have suggested that Gly, Ala, Asp, Val, Ser, Pro, Glu, Leu, Thr may belong to a group of amino acids that constituted the early genetic code, whereas Cys, Met, Tyr, Trp, His, Phe may belong to a group of amino acids that constituted later additions of the genetic code.[79] [80] [81]

Standard and nonstandard forms

The 20 amino acids that are encoded directly by the codons of the universal genetic code are called standard or canonical amino acids.[82] [83] A modified form of methionine (N-formylmethionine) is often incorporated in place of methionine as the initial amino acid of proteins in bacteria, mitochondria and plastids (including chloroplasts).[84] Other amino acids are called nonstandard or non-canonical.[85] Most of the nonstandard amino acids are also non-proteinogenic (i.e. they cannot be incorporated into proteins during translation), but two of them are proteinogenic, as they can be incorporated translationally into proteins by exploiting information not encoded in the universal genetic code.[86]

The two nonstandard proteinogenic amino acids are selenocysteine (present in many non-eukaryotes as well as most eukaryotes, but not coded directly by DNA) and pyrrolysine (found only in some archaea and at least one bacterium).[87] [88] The incorporation of these nonstandard amino acids is rare. For example, 25 human proteins include selenocysteine in their primary structure,[89] and the structurally characterized enzymes (selenoenzymes) employ selenocysteine as the catalytic moiety in their active sites.[90] Pyrrolysine and selenocysteine are encoded via variant codons. For example, selenocysteine is encoded by stop codon and SECIS element.[91] [92] [93]

N-formylmethionine (which is often the initial amino acid of proteins in bacteria, mitochondria, and chloroplasts) is generally considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–tRNA combinations not found in nature can also be used to "expand" the genetic code and form novel proteins known as alloproteins incorporating non-proteinogenic amino acids.[94] [95] [96]

Non-proteinogenic

See main article: Non-proteinogenic amino acids.

Aside from the 22 proteinogenic amino acids, many non-proteinogenic amino acids are known.[97] [98] These either are not found in proteins (for example carnitine, GABA, ornithine) or are not produced directly and in isolation by standard cellular machinery. For example, hydroxyproline is synthesized from proline,[99] and selenomethionine is produced by metabolic modification of methionine.[100]

Non-proteinogenic amino acids that are found in proteins are formed by post-translational modification. Such modifications can also determine the localization of the protein, e.g., the addition of long hydrophobic groups can cause a protein to bind to a phospholipid membrane.[101] Examples:

Some non-proteinogenic amino acids are not found in proteins. Examples include 2-aminoisobutyric acid and the neurotransmitter gamma-aminobutyric acid. Non-proteinogenic amino acids often occur as intermediates in the metabolic pathways for standard amino acids – for example, ornithine and citrulline occur in the urea cycle, part of amino acid catabolism (see below).[105] A rare exception to the dominance of α-amino acids in biology is the β-amino acid beta alanine (3-aminopropanoic acid), which is used in plants and microorganisms in the synthesis of pantothenic acid (vitamin B5), a component of coenzyme A.[106]

Physiological roles beyond proteins

Many proteinogenic and non-proteinogenic amino acids have biological functions beyond being precursors to proteins and peptides. In humans, amino acids also have important roles in diverse biosynthetic pathways. Defenses against herbivores in plants sometimes employ amino acids.[107] Examples:

Standard

Nonstandard

However, not all of the functions of other abundant nonstandard amino acids are known.[127]

In mammalian nutrition

See main article: Essential amino acid.

Animals ingest amino acids in the form of protein. The protein is broken down into its constituent amino acids in the process of digestion. The amino acids are then used to synthesize new proteins and other nitrogenous biomolecules, or they are further catabolized through oxidation to provide a source of energy.[128] The oxidation pathway starts with the removal of the amino group by a transaminase; the amino group is then fed into the urea cycle. The other product of transamidation is a keto acid that enters the citric acid cycle.[129] Glucogenic amino acids can also be converted into glucose, through gluconeogenesis.[130]

Of the 20 standard amino acids, nine (His, Ile, Leu, Lys, Met, Phe, Thr, Trp and Val) are called essential amino acids because the human body cannot synthesize them from other compounds at the level needed for normal growth, so they must be obtained from food.[131] [132] [133]

Conditional requirements

In addition, cysteine, tyrosine, and arginine are considered semiessential amino acids, and taurine a semi-essential aminosulfonic acid in children. Some amino acids are conditionally essential for certain ages or medical conditions. Essential amino acids may also vary from species to species. The metabolic pathways that synthesize these monomers are not fully developed.[134] [135]

Industrial uses

Animal feed

Amino acids are sometimes added to animal feed because some of the components of these feeds, such as soybeans, have low levels of some of the essential amino acids, especially of lysine, methionine, threonine, and tryptophan.[136] Likewise amino acids are used to chelate metal cations in order to improve the absorption of minerals from feed supplements.[137]

Food

The food industry is a major consumer of amino acids, especially glutamic acid, which is used as a flavor enhancer,[138] and aspartame (aspartylphenylalanine 1-methyl ester), which is used as an artificial sweetener.[139] Amino acids are sometimes added to food by manufacturers to alleviate symptoms of mineral deficiencies, such as anemia, by improving mineral absorption and reducing negative side effects from inorganic mineral supplementation.

Chemical building blocks

Amino acids are low-cost feedstocks used in chiral pool synthesis as enantiomerically pure building blocks.[140] [141]

Amino acids are used in the synthesis of some cosmetics.[136]

Potential uses

Fertilizer

The chelating ability of amino acids is sometimes used in fertilizers to facilitate the delivery of minerals to plants in order to correct mineral deficiencies, such as iron chlorosis. These fertilizers are also used to prevent deficiencies from occurring and to improve the overall health of the plants.[142]

Biodegradable plastics

Amino acids have been considered as components of biodegradable polymers, which have applications as environmentally friendly packaging and in medicine in drug delivery and the construction of prosthetic implants.[143] An interesting example of such materials is polyaspartate, a water-soluble biodegradable polymer that may have applications in disposable diapers and agriculture.[144] Due to its solubility and ability to chelate metal ions, polyaspartate is also being used as a biodegradable antiscaling agent and a corrosion inhibitor.[145] [146]

Synthesis

See main article: Amino acid synthesis.

Chemical synthesis

The commercial production of amino acids usually relies on mutant bacteria that overproduce individual amino acids using glucose as a carbon source. Some amino acids are produced by enzymatic conversions of synthetic intermediates. 2-Aminothiazoline-4-carboxylic acid is an intermediate in one industrial synthesis of L-cysteine for example. Aspartic acid is produced by the addition of ammonia to fumarate using a lyase.

Biosynthesis

In plants, nitrogen is first assimilated into organic compounds in the form of glutamate, formed from alpha-ketoglutarate and ammonia in the mitochondrion. For other amino acids, plants use transaminases to move the amino group from glutamate to another alpha-keto acid. For example, aspartate aminotransferase converts glutamate and oxaloacetate to alpha-ketoglutarate and aspartate.[147] Other organisms use transaminases for amino acid synthesis, too.[148] [149]

Nonstandard amino acids are usually formed through modifications to standard amino acids. For example, homocysteine is formed through the transsulfuration pathway or by the demethylation of methionine via the intermediate metabolite S-adenosylmethionine,[150] while hydroxyproline is made by a post translational modification of proline.[151]

Microorganisms and plants synthesize many uncommon amino acids. For example, some microbes make 2-aminoisobutyric acid and lanthionine, which is a sulfide-bridged derivative of alanine. Both of these amino acids are found in peptidic lantibiotics such as alamethicin.[152] However, in plants, 1-aminocyclopropane-1-carboxylic acid is a small disubstituted cyclic amino acid that is an intermediate in the production of the plant hormone ethylene.[153]

Primordial synthesis

The formation of amino acids and peptides is assumed to have preceded and perhaps induced the emergence of life on earth. Amino acids can form from simple precursors under various conditions. Surface-based chemical metabolism of amino acids and very small compounds may have led to the build-up of amino acids, coenzymes and phosphate-based small carbon molecules.[154] [155] Amino acids and similar building blocks could have been elaborated into proto-peptides, with peptides being considered key players in the origin of life.[156]

In the famous Urey-Miller experiment, the passage of an electric arc through a mixture of methane, hydrogen, and ammonia produces a large number of amino acids. Since then, scientists have discovered a range of ways and components by which the potentially prebiotic formation and chemical evolution of peptides may have occurred, such as condensing agents, the design of self-replicating peptides and a number of non-enzymatic mechanisms by which amino acids could have emerged and elaborated into peptides.[156] Several hypotheses invoke the Strecker synthesis whereby hydrogen cyanide, simple aldehydes, ammonia, and water produce amino acids.[157]

According to a review, amino acids, and even peptides, "turn up fairly regularly in the various experimental broths that have been allowed to be cooked from simple chemicals. This is because nucleotides are far more difficult to synthesize chemically than amino acids." For a chronological order, it suggests that there must have been a 'protein world' or at least a 'polypeptide world', possibly later followed by the 'RNA world' and the 'DNA world'.[158] Codon–amino acids mappings may be the biological information system at the primordial origin of life on Earth.[159] While amino acids and consequently simple peptides must have formed under different experimentally probed geochemical scenarios, the transition from an abiotic world to the first life forms is to a large extent still unresolved.[160]

Reactions

Amino acids undergo the reactions expected of the constituent functional groups.[161] [162]

Peptide bond formation

See also: Peptide synthesis and Peptide bond.

As both the amine and carboxylic acid groups of amino acids can react to form amide bonds, one amino acid molecule can react with another and become joined through an amide linkage. This polymerization of amino acids is what creates proteins. This condensation reaction yields the newly formed peptide bond and a molecule of water. In cells, this reaction does not occur directly; instead, the amino acid is first activated by attachment to a transfer RNA molecule through an ester bond. This aminoacyl-tRNA is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase.[163] This aminoacyl-tRNA is then a substrate for the ribosome, which catalyzes the attack of the amino group of the elongating protein chain on the ester bond.[164] As a result of this mechanism, all proteins made by ribosomes are synthesized starting at their N-terminus and moving toward their C-terminus.[165]

However, not all peptide bonds are formed in this way. In a few cases, peptides are synthesized by specific enzymes. For example, the tripeptide glutathione is an essential part of the defenses of cells against oxidative stress. This peptide is synthesized in two steps from free amino acids.[166] In the first step, gamma-glutamylcysteine synthetase condenses cysteine and glutamate through a peptide bond formed between the side chain carboxyl of the glutamate (the gamma carbon of this side chain) and the amino group of the cysteine. This dipeptide is then condensed with glycine by glutathione synthetase to form glutathione.[167]

In chemistry, peptides are synthesized by a variety of reactions. One of the most-used in solid-phase peptide synthesis uses the aromatic oxime derivatives of amino acids as activated units. These are added in sequence onto the growing peptide chain, which is attached to a solid resin support.[168] Libraries of peptides are used in drug discovery through high-throughput screening.[169]

The combination of functional groups allow amino acids to be effective polydentate ligands for metal–amino acid chelates.[170] The side chains of amino acids can also undergo posttranslational chemical reactions.[171] [172] [173]

Catabolism

Degradation of an amino acid often begins with transamination, in which its amino group is transferred to α-ketoglutarate, forming glutamate. This process involves transaminases, often the same enzymes used in amino acid synthesis. In many vertebrates, the amino group is subsequently released as ammonia and converted to urea via the urea cycle for excretion. However, amino acid degradation can result in uric acid or ammonia instead, depending on the organism. For example, serine dehydratase converts serine directly to pyruvate and ammonia. After removal of one or more amino groups, the remaining carbon skeleton of an amino acid can serve as a precursor for synthesizing other amino acids, be further metabolized for energy after conversion into intermediates of glycolysis (typically via gluconeogenesis) or of the citric acid cycle, or be used for fatty acid synthesis and storage as triacylglycerol.[174] [175]

Complexation

Amino acids are bidentate ligands, forming transition metal amino acid complexes.[176]

Chemical analysis

The total nitrogen content of organic matter is mainly formed by the amino groups in proteins. The total Kjeldahl nitrogen (TKN) is a measure of nitrogen widely used in the analysis of (waste) water, soil, food, feed and organic matter in general. As the name suggests, the Kjeldahl method is applied. More sensitive methods are available.[177] [178]

See also

Further reading

Notes and References

  1. Book: Lehninger AL . Biochemistry: the molecular basis of cell structure and function . 1975 . Worth Publishers . New York . 0-87901-047-9 . 2nd.
  2. Flissi A, Ricart E, Campart C, Chevalier M, Dufresne Y, Michalik J, Jacques P, Flahaut C, Lisacek F, Leclère V, Pupin M . Norine: update of the nonribosomal peptide resource . Nucleic Acids Research . 48 . D1 . D465–D469 . January 2020 . 31691799 . 7145658 . 10.1093/nar/gkz1000 .
  3. Web site: 2009 . Cammack R . Newsletter 2009 . https://web.archive.org/web/20170912194130/http://www.chem.qmul.ac.uk/iubmb/newsletter/2009.html#item35 . 2017-09-12 . 2012-04-16 . Biochemical Nomenclature Committee of IUPAC and NC-IUBMB . Pyrrolysine.
  4. Rother M, Krzycki JA . Selenocysteine, pyrrolysine, and the unique energy metabolism of methanogenic archaea . Archaea . 2010 . 1–14 . August 2010 . 20847933 . 2933860 . 10.1155/2010/453642 . free .
  5. Book: Human nutrition in the developing world . Latham MC . Food and Agriculture Organization of the United Nations . 1997 . Rome . Chapter 8. Body composition, the functions of food, metabolism and energy . http://www.fao.org/docrep/W0073E/w0073e04.htm#P1625_217364 . Food and Nutrition Series – No. 29. 9 September 2012. 8 October 2012. https://web.archive.org/web/20121008212843/http://www.fao.org/docrep/W0073e/w0073e04.htm#P1625_217364 .
  6. Book: Luisi PL . Pier Luigi Luisi . 13 July 2006 . The Emergence of Life: From Chemical Origins to Synthetic Biology . Cambridge University Press . 13 . 978-1-139-45564-0 . 5 August 2024 . Of course if on Earth there had only been diketopiperazines and not amino acids; or if sugars did not have the size they have; or if lipids were three times shorter, then we would not have life. .
  7. Web site: Nomenclature and Symbolism for Amino Acids and Peptides . IUPAC-IUB Joint Commission on Biochemical Nomenclature . 1983 . 17 November 2008 . https://web.archive.org/web/20081009023202/http://www.chem.qmul.ac.uk/iupac/AminoAcid/AA1n2.html . 9 October 2008 .
  8. Vickery HB, Schmidt CL . 1931 . The history of the discovery of the amino acids . Chem. Rev. . 9 . 2. 169–318 . 10.1021/cr60033a001.
  9. Web site: Hansen S . Die Entdeckung der proteinogenen Aminosäuren von 1805 in Paris bis 1935 in Illinois . Berlin . May 2015 . https://web.archive.org/web/20171201232937/https://www.arginium.de/wp-content/uploads/2015/12/Entdeckung-der-Aminos%C3%A4uren.pdf . 1 December 2017 . de.
  10. The discovery of a new plant principle in Asparagus sativus . Vauquelin LN, Robiquet PJ . Annales de Chimie . 1806 . 57 . 88–93.
  11. Book: Advances in Protein Chemistry . Anfinsen CB, Edsall JT, Richards FM . 1972 . 99, 103 . Academic Press . New York . 978-0-12-034226-6 .
  12. On cystic oxide, a new species of urinary calculus . Wollaston WH . 110151163 . Philosophical Transactions of the Royal Society . 1810 . 100. 145 . 223–230 . 10.1098/rstl.1810.0015. 30493165 . 5699749 .
  13. Über cystin und cystein . Baumann E . Z Physiol Chem . 1884 . 8 . 4 . 299–305 . 28 March 2011 . https://web.archive.org/web/20110314075450/http://vlp.mpiwg-berlin.mpg.de/library/data/lit16533 . 14 March 2011 .
  14. Sur la conversion des matières animales en nouvelles substances par le moyen de l'acide sulfurique . Braconnot HM . Annales de Chimie et de Physique . 2nd Series . 1820 . 13 . 113–125.
  15. Simoni RD, Hill RL, Vaughan M . The discovery of the amino acid threonine: the work of William C. Rose [classical article] . The Journal of Biological Chemistry . 277 . 37 . E25 . September 2002 . 12218068 . 10.1016/S0021-9258(20)74369-3 . free .
  16. Feeding Experiments with Mixtures of Highly Purified Amino Acids. VIII. Isolation and Identification of a New Essential Amino Acid. McCoy RH, Meyer CE, Rose WC. 1935. Journal of Biological Chemistry. 112. 283–302. 10.1016/S0021-9258(18)74986-7. free.
  17. Menten, P. Dictionnaire de chimie: Une approche étymologique et historique. De Boeck, Bruxelles. link .
  18. Web site: amino- . Harper D . Online Etymology Dictionary . 19 July 2010 . 2 December 2017 . https://web.archive.org/web/20171202102757/https://www.etymonline.com/word/amino- . live .
  19. Paal C . 1894 . Ueber die Einwirkung von Phenyl-i-cyanat auf organische Aminosäuren . Berichte der Deutschen Chemischen Gesellschaft . 27 . 974–979 . 10.1002/cber.189402701205 . https://web.archive.org/web/20200725075835/https://zenodo.org/record/1425732 . 2020-07-25 .
  20. Book: Fruton JS . Contrasts in Scientific Style: Research Groups in the Chemical and Biochemical Sciences . 191 . 1990 . Chapter 5- Emil Fischer and Franz Hofmeister . https://books.google.com/books?id=tRlC9NyNNN8C&pg=PA163 . 163–165 . American Philosophical Society . 978-0-87169-191-0 .
  21. Web site: Alpha amino acid . Merriam-Webster Medical . 3 January 2015. 3 January 2015. https://web.archive.org/web/20150103191856/http://www.merriam-webster.com/medical/alpha-amino%20acid. live. .
  22. Web site: Clark J . August 2007 . An introduction to amino acids . chemguide . 4 July 2015 . live . 30 April 2015. https://web.archive.org/web/20150430051143/http://www.chemguide.co.uk/organicprops/aminoacids/background.html.
  23. Encyclopedia: 2008. Amino acids . Peptides from A to Z: A Concise Encyclopedia . Wiley-VCH. Germany. 978-3-527-62117-0 . Google Books. 20. Jakubke HD, Sewald N . 5 January 2016. 17 May 2016. https://web.archive.org/web/20160517144350/https://books.google.com/books?id=doe9NwgJTAsC&pg=PA20. live.
  24. Book: Pollegioni L, Servi S . Unnatural Amino Acids: Methods and Protocols. 2012. Humana Press. 978-1-61779-331-8. v. 756512314. Methods in Molecular Biology . 794. 10.1007/978-1-61779-331-8. 3705304 .
  25. Hertweck C . Biosynthesis and charging of pyrrolysine, the 22nd genetically encoded amino acid . Angewandte Chemie . 50 . 41 . 9540–9541 . October 2011 . 21796749 . 10.1002/anie.201103769 . 2011ACIE...50.9540H . 5359077 .
  26. Web site: Chapter 1: Proteins are the Body's Worker Molecules . 27 October 2011 . The Structures of Life . National Institute of General Medical Sciences . 20 May 2008 . 7 June 2014 . https://web.archive.org/web/20140607084902/https://publications.nigms.nih.gov/structlife/chapter1.html.
  27. Book: Walsh CT, Tang Y . Chapter 5: Peptide Natural Products II: Nonribosomal Peptides . Natural product biosynthesis: chemical logic and enzymatic machinery . 2023 . Royal Society of Chemistry . London . 978-1-83916-801-7 . 10.1039/BK9781839165641-00150 . 150–191 . 2nd.
  28. Zhong Q, Xiao X, Qiu Y, Xu Z, Chen C, Chong B, Zhao X, Hai S, Li S, An Z, Dai L . Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications . Medcomm . 4 . 3 . e261 . June 2023 . 37143582 . 10.1002/mco2.261 . 10152985 .
  29. Book: Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology . Wiley-Blackwell . 2012 . 978-0-470-14684-2 . Oxford . Michal G, Schomburg D . 5 . 2nd .
  30. Book: Creighton TH . Proteins: structures and molecular properties . W. H. Freeman . San Francisco . 1993 . Chapter 1 . 978-0-7167-7030-5 . registration . https://archive.org/details/proteinsstructur0000crei .
  31. Genchi G . An overview on D-amino acids . Amino Acids . 49 . 9 . 1521–1533 . September 2017 . 28681245 . 10.1007/s00726-017-2459-5 . 254088816 .
  32. Book: Garrett RH, Grisham CM . Biochemistry . 2010 . Brooks/Cole, Cengage Learning . 978-0-495-10935-8 . 4th . Belmont, CA . 74,134–176,430–442 . 297392560.
  33. Novikov AP, Safonov AV, German KE, Grigoriev MS . 2023-12-01 . What kind of interactions we may get moving from zwitter to "dritter" ions: C–O⋯Re(O4) and Re–O⋯Re(O4) anion⋯anion interactions make structural difference between L-histidinium perrhenate and pertechnetate . CrystEngComm . 26 . 61–69 . en . 10.1039/D3CE01164J . 265572280 . 1466-8033.
  34. Book: Ahern K, Rajagopal I, Tan T . Biochemistry Free For All . 4.3: Mechanisms of Catalysis . Biology LibreTexts, LibreTexts . 21 March 2024 . https://bio.libretexts.org/Bookshelves/Biochemistry/Book:_Biochemistry_Free_For_All_(Ahern_Rajagopal_and_Tan)/04:_Catalysis/4.03:_Mechanisms_of_Catalysis .
  35. Dunn BM . Structure and mechanism of the pepsin-like family of aspartic peptidases . Chemical Reviews . 102 . 12 . 4431–4458 . December 2002 . 12475196 . 10.1021/cr010167q . 2002ChRv..102.4431D .
  36. Book: McMurry J . Stereochemistry at Tetrahedral Centers: Diastereomers . https://openstax.org/books/organic-chemistry/pages/5-6-diastereomers . Organic chemistry . 2023 . OpenStax . Houston, Texas . 978-1-951693-98-5 . 10th.
  37. Koide S, Sidhu SS . The importance of being tyrosine: lessons in molecular recognition from minimalist synthetic binding proteins . ACS Chemical Biology . 4 . 5 . 325–334 . May 2009 . 19298050 . 10.1021/cb800314v . 2829252 .
  38. Papp LV, Lu J, Holmgren A, Khanna KK . From selenium to selenoproteins: synthesis, identity, and their role in human health . Antioxidants & Redox Signaling . 9 . 7 . 775–806 . July 2007 . 17508906 . 10.1089/ars.2007.1528 .
  39. Hao B, Gong W, Ferguson TK, James CM, Krzycki JA, Chan MK . A new UAG-encoded residue in the structure of a methanogen methyltransferase . Science . 296 . 5572 . 1462–1466 . May 2002 . 12029132 . 10.1126/science.1069556 . 35519996 . 2002Sci...296.1462H .
  40. Gaston MA, Jiang R, Krzycki JA . Functional context, biosynthesis, and genetic encoding of pyrrolysine . Current Opinion in Microbiology . 14 . 3 . 342–349 . June 2011 . 21550296 . 3119745 . 10.1016/j.mib.2011.04.001 .
  41. Ntountoumi C, Vlastaridis P, Mossialos D, Stathopoulos C, Iliopoulos I, Promponas V, Oliver SG, Amoutzias GD . Low complexity regions in the proteins of prokaryotes perform important functional roles and are highly conserved . Nucleic Acids Research . 47 . 19 . 9998–10009 . November 2019 . 31504783 . 6821194 . 10.1093/nar/gkz730 .
  42. Urry DW . The change in Gibbs free energy for hydrophobic association: Derivation and evaluation by means of inverse temperature transitions . Chemical Physics Letters . 399 . 1–3 . 177–183 . 2004 . 10.1016/S0009-2614(04)01565-9 . 2004CPL...399..177U .
  43. Stollar EJ, Smith DP . Correction: Uncovering protein structure . Essays in Biochemistry . 65 . 2 . 407 . July 2021 . 34269795 . 10.1042/EBC-2019-0042C_COR . 8313991 .
  44. Marcotte EM, Pellegrini M, Yeates TO, Eisenberg D . A census of protein repeats . Journal of Molecular Biology . 293 . 1 . 151–160 . October 1999 . 10512723 . 10.1006/jmbi.1999.3136 . 1999JMBio.293..151M .
  45. Haerty W, Golding GB . Low-complexity sequences and single amino acid repeats: not just "junk" peptide sequences . Genome . 53 . 10 . 753–762 . October 2010 . 20962881 . 10.1139/G10-063 . Bonen L .
  46. Magee T, Seabra MC . Fatty acylation and prenylation of proteins: what's hot in fat . Current Opinion in Cell Biology . 17 . 2 . 190–196 . April 2005 . 15780596 . 10.1016/j.ceb.2005.02.003 .
  47. Pilobello KT, Mahal LK . Deciphering the glycocode: the complexity and analytical challenge of glycomics . Current Opinion in Chemical Biology . 11 . 3 . 300–305 . June 2007 . 17500024 . 10.1016/j.cbpa.2007.05.002 .
  48. Smotrys JE, Linder ME . Palmitoylation of intracellular signaling proteins: regulation and function . Annual Review of Biochemistry . 73 . 1 . 559–587 . 2004 . 15189153 . 10.1146/annurev.biochem.73.011303.073954 . 2004ARBio..73..559S .
  49. Book: Steinhardt J, Reynolds JA . Multiple equilibria in proteins . Academic Press . New York . 978-0-12-665450-9. 176–21 . 1969.
  50. Li Q, Wen C, Yang J, Zhou X, Zhu Y, Zheng J, Cheng G, Bai J, Xu T, Ji J, Jiang S, Zhang L, Zhang P . Zwitterionic Biomaterials . Chemical Reviews . 122 . 23 . 17073–17154 . December 2022 . 36201481 . 10.1021/acs.chemrev.2c00344 . 2022ChRv..12217073L .
  51. Kim JY, Ahn DS, Park SW, Lee S . Gas phase hydration of amino acids and dipeptides: effects on the relative stability of zwitterion vs. canonical conformers. . RSC Advances . 2014 . 4 . 31 . 16352–16361 . 10.1039/C4RA01217H . 2014RSCAd...416352K .
  52. Book: Harvey D, Clark J . 3.7: The Effect of pH on Enzyme Kinetics . Chem 107B: Physical Chemistry for Life Scientists . Chemistry LibreTexts . 2023 . https://chem.libretexts.org/Courses/University_of_California_Davis/Chem_107B%3A_Physical_Chemistry_for_Life_Scientists/Chapters/3%3A_Enzyme_Kinetics/3.7%3A_The_Effect_of_pH_on_Enzyme_Kinetics . 7 December 2025 .
  53. Book: Dawson JF . 2021 . Amino Acid Properties: Polarity and Ionization . https://ecampusontario.pressbooks.pub/bioc2580/chapter/bioc2580-lecture-2-amino-acid-properties-polarity-and-ionization/ . BIOC 2580: Introduction to Biochemistry. . Pressbooks .
  54. Brønsted JN . Recueil des Travaux Chimiques des Pays-Bas . 42 . 718–728 . 1923. Einige Bemerkungen über den Begriff der Säuren und Basen. 8 . 10.1002/recl.19230420815 . Remarks on the concept of acids and bases.
  55. Holliday GL, Mitchell JB, Thornton JM . Understanding the functional roles of amino acid residues in enzyme catalysis . Journal of Molecular Biology . 390 . 3 . 560–577 . July 2009 . 19447117 . 10.1016/j.jmb.2009.05.015 .
  56. Book: Fennema OR . Food Chemistry 3rd Ed . CRC Press . 327–328 . 978-0-8247-9691-4 . 1996-06-19 .
  57. Book: Vollhardt KP, Schore NE . Organic chemistry: structure and function . 2007 . W.H. Freeman . 978-0-7167-9949-8 . 5th . New York . 58–66 . 61448218.
  58. Pergande MR, Cologna SM . Isoelectric Point Separations of Peptides and Proteins . Proteomes . 5 . 1 . 4 . January 2017 . 28248255 . 10.3390/proteomes5010004 . 5372225 . free .
  59. Book: Zwitterions . https://archive.org/details/TheEncyclopediaOfBiochemistry/page/n189/mode/2up . The Encyclopedia of Biochemistry . Creighton TE . Reinhold Publishing / Van Nostrand Reinhold . 1967 . 358 . Zwitterions have minimal solubility at their isolectric point and amino acids are often isolated by precipitation from water after adjusting the pH to their isolectric point. .
  60. 10 July 1968 . IUPAC-IUB Commission on Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences . Journal of Biological Chemistry . en . 243 . 13 . 3557–3559 . 10.1016/S0021-9258(19)34176-6. free .
  61. Saffran M . April 1998 . Amino acid names and parlor games: from trivial names to a one-letter code, amino acid names have strained students' memories. Is a more rational nomenclature possible? . Biochemical Education . en . 26 . 2 . 116–118 . 10.1016/S0307-4412(97)00167-2.
  62. Adoga GI, Nicholson BH . January 1988 . Letters to the editor . Biochemical Education . en . 16 . 1 . 49 . 10.1016/0307-4412(88)90026-X.
  63. Kyte J, Doolittle RF . A simple method for displaying the hydropathic character of a protein . Journal of Molecular Biology . 157 . 1 . 105–132 . May 1982 . 7108955 . 10.1016/0022-2836(82)90515-0 . 10.1.1.458.454 .
  64. Book: Physical Biochemistry. Freifelder D. W. H. Freeman and Company. 978-0-7167-1315-9. 2nd. 1983.
  65. Kozlowski LP . Proteome-pI: proteome isoelectric point database . Nucleic Acids Research . 45 . D1 . D1112–D1116 . January 2017 . 27789699 . 5210655 . 10.1093/nar/gkw978 .
  66. Book: Hausman RE, Cooper GM . The cell: a molecular approach . ASM Press . Washington, D.C. . 2004 . 51 . 978-0-87893-214-6.
  67. Yuan J, O'Donoghue P, Ambrogelly A, Gundllapalli S, Sherrer RL, Palioura S, Simonović M, Söll D . Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl-tRNA formation systems . FEBS Letters . 584 . 2 . 342–349 . January 2010 . 19903474 . 2795046 . 10.1016/j.febslet.2009.11.005 . 2010FEBSL.584..342Y .
  68. Aasland R, Abrams C, Ampe C, Ball LJ, Bedford MT, Cesareni G, Gimona M, Hurley JH, Jarchau T, Lehto VP, Lemmon MA, Linding R, Mayer BJ, Nagai M, Sudol M, Walter U, Winder SJ . Normalization of nomenclature for peptide motifs as ligands of modular protein domains . FEBS Letters . 513 . 1 . 141–144 . February 2002 . 11911894 . 10.1111/j.1432-1033.1968.tb00350.x .
  69. IUPAC–IUB Commission on Biochemical Nomenclature . A one-letter notation for amino acid sequences . Pure and Applied Chemistry . 31 . 4 . 641–645 . 1972 . 5080161 . 10.1351/pac197231040639 . free .
  70. Book: Standard ST.26: Recommended Standard for the Presentation of Nucleotide and Amino Acid Sequence Listings Using XML (Extensible Markup Language) . Version 2.0 . World Intellectual Property Organization . 2025 . Geneva, Switzerland . 3.26.vi.22 . PDF . 23 December 2025 .
  71. Web site: UNK Ligand Summary . Chemical Component Dictionary . RCSB Protein Data Bank . 23 December 2025 .
  72. Book: Velíšek J, Koplík R, Cejpek K . Amino acids, Peptides, and Proteins . https://books.google.com/books?id=Il_wDwAAQBAJ . The Chemistry of Food . 2020 . Wiley-Blackwell/John Wiley & Sons Ltd . Chichester, West Sussex . 978-1-119-53764-9 . Second . Table 2.1: In addition to the specific amino acid codes, three-letter code, and one letter-code, placeholders are used tor ambiguous amino acids, e.g. Asx and B for aspartic acid or asparagine, Glx for glutamic acid and glutamine, Xle and J for leucine and isoleucine, and Xaa (Unk) and X for unspecified (unknown) amino acid. . 6 .
  73. Web site: Sequence Variant Nomenclature, Protein Recommendations . 23 September 2021 . Human Genome Variation Society (HGVS) . live . 24 September 2021 . https://web.archive.org/web/20210924091505/http://varnomen.hgvs.org/recommendations/protein/variant/substitution/.
  74. Suchanek M, Radzikowska A, Thiele C . Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells . Nature Methods . 2 . 4 . 261–267 . April 2005 . 15782218 . 10.1038/nmeth752 . free .
  75. Rodnina MV, Beringer M, Wintermeyer W . How ribosomes make peptide bonds . Trends in Biochemical Sciences . 32 . 1 . 20–26 . January 2007 . 17157507 . 10.1016/j.tibs.2006.11.007 .
  76. Book: Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P . From RNA to Protein. . https://www.ncbi.nlm.nih.gov/books/NBK26829/ . Molecular Biology of the Cell . 4th . New York . Garland Science . 2002 . 978-0-8153-3218-3 .
  77. Driscoll DM, Copeland PR . Mechanism and regulation of selenoprotein synthesis . Annual Review of Nutrition . 23 . 1 . 17–40 . 2003 . 12524431 . 10.1146/annurev.nutr.23.011702.073318 . 2003ARNut..23...17D .
  78. Krzycki JA . The direct genetic encoding of pyrrolysine . Current Opinion in Microbiology . 8 . 6 . 706–712 . December 2005 . 16256420 . 10.1016/j.mib.2005.10.009 .
  79. Wong JT . A co-evolution theory of the genetic code . Proceedings of the National Academy of Sciences of the United States of America . 72 . 5 . 1909–1912 . May 1975 . 1057181 . 432657 . 10.1073/pnas.72.5.1909 . free . 1975PNAS...72.1909T .
  80. Trifonov EN . Consensus temporal order of amino acids and evolution of the triplet code . Gene . 261 . 1 . 139–151 . December 2000 . 11164045 . 10.1016/S0378-1119(00)00476-5 .
  81. Higgs PG, Pudritz RE . A thermodynamic basis for prebiotic amino acid synthesis and the nature of the first genetic code . Astrobiology . 9 . 5 . 483–490 . June 2009 . 19566427 . 10.1089/ast.2008.0280 . 0904.0402 . 9039622 . 2009AsBio...9..483H .
  82. Lobanov AV, Kryukov GV, Hatfield DL, Gladyshev VN . Is there a twenty third amino acid in the genetic code? . Trends in Genetics . 22 . 7 . 357–60 . July 2006 . 16713651 . 10.1016/j.tig.2006.05.002 .
  83. Doig AJ . Frozen, but no accident - why the 20 standard amino acids were selected . The FEBS Journal . 284 . 9 . 1296–1305 . May 2017 . 27926995 . 10.1111/febs.13982 .
  84. Alvarenga L, Cardozo LF, Ribeiro M, Kussi F, Esgalhado M, Mafra D . Bioactive Compounds as Modulators of N-Formyl Peptide Signaling in Chronic Diseases . Molecules (Basel, Switzerland) . 30 . 14 . July 2025 . 2981 . 40733247 . 12298040 . 10.3390/molecules30142981 . free .
  85. Rezhdo A, Islam M, Huang M, Van Deventer JA . Future prospects for noncanonical amino acids in biological therapeutics . Current Opinion in Biotechnology . 60 . 168–178 . December 2019 . 30974337 . 10.1016/j.copbio.2019.02.020 . 6783319 .
  86. Hatfield DL, Gladyshev VN . How selenium has altered our understanding of the genetic code . Molecular and Cellular Biology . 22 . 11 . 3565–76 . June 2002 . 11997494 . 133838 . 10.1128/MCB.22.11.3565-3576.2002 . 2002MolCB..22.3565H .
  87. Lukashenko NP . [Expanding genetic code: amino acids 21 and 22--selenocysteine and pyrrolysine] . Genetika . 46 . 8 . 1013–1032 . August 2010 . 20873198 . Russian .
  88. Zhang Y, Gladyshev VN . High content of proteins containing 21st and 22nd amino acids, selenocysteine and pyrrolysine, in a symbiotic deltaproteobacterium of gutless worm Olavius algarvensis . Nucleic Acids Research . 35 . 15 . 4952–4963 . 2007 . 17626042 . 1976440 . 10.1093/nar/gkm514 .
  89. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigó R, Gladyshev VN . Characterization of mammalian selenoproteomes . Science . 300 . 5624 . 1439–1443 . May 2003 . 12775843 . 10.1126/science.1083516 . 10363908 . 2003Sci...300.1439K .
  90. Gromer S, Urig S, Becker K . The thioredoxin system--from science to clinic . Medicinal Research Reviews . 24 . 1 . 40–89 . January 2004 . 14595672 . 10.1002/med.10051 . 1944741 .
  91. Tjong H . Modeling Electrostatic Contributions to Protein Folding and Binding . 1 footnote . 2008 . Florida State University . PhD thesis . 28 January 2020 . 28 January 2020 . https://web.archive.org/web/20200128234717/https://diginole.lib.fsu.edu/islandora/object/fsu:175939 . live .
  92. Book: Stewart L, Burgin AB . Whole Gene Synthesis: A Gene-O-Matic Future . Frontiers in Drug Design & Discovery . 1 . 299 . 2005 . 10.2174/1574088054583318 . https://books.google.com/books?id=VoJw6fIISSkC&pg=PA299 . . 978-1-60805-199-1 . 1574-0889 . 5 January 2016 . 14 April 2021 . https://web.archive.org/web/20210414224011/https://books.google.com/books?id=VoJw6fIISSkC&pg=PA299 . live . subscription .
  93. Web site: Elzanowski A, Ostell J . The Genetic Codes . 7 April 2008 . 10 March 2010 . National Center for Biotechnology Information (NCBI) . 20 August 2016 . https://web.archive.org/web/20160820125755/http://130.14.29.110/Taxonomy/Utils/wprintgc.cgi?mode=c . live .
  94. Xie J, Schultz PG . Adding amino acids to the genetic repertoire . Current Opinion in Chemical Biology . 9 . 6 . 548–554 . December 2005 . 16260173 . 10.1016/j.cbpa.2005.10.011 .
  95. Wang Q, Parrish AR, Wang L . Expanding the genetic code for biological studies . Chemistry & Biology . 16 . 3 . 323–336 . March 2009 . 19318213 . 2696486 . 10.1016/j.chembiol.2009.03.001 .
  96. Book: Simon M . Emergent computation: emphasizing bioinformatics . limited . AIP Press/Springer Science+Business Media . New York . 2005 . 105–106 . 978-0-387-22046-8 .
  97. Book: Barrett GC, Elmore DT . Introduction: Non-proteinogenic amino acids . Amino Acids and Peptides . 1998 . Cambridge University Press . Cambridge New York . 978-0-521-46292-1 .
  98. Bell EA, Watson AA, Nash RJ . Non-protein amino acids: a review of the biosynthesis and taxonomic significance. . Natural Product Communications . June 2008 . 3 . 1 . 91–110 . 10.1177/1934578X0800300 . 9 December 2025 .
  99. Belostotsky R, Frishberg Y . Catabolism of Hydroxyproline in Vertebrates: Physiology, Evolution, Genetic Diseases and New siRNA Approach for Treatment . International Journal of Molecular Sciences . 23 . 2 . January 2022 . 1005 . 35055190 . 10.3390/ijms23021005 . 8779045 . free .
  100. Schrauzer GN . Selenomethionine: a review of its nutritional significance, metabolism and toxicity . The Journal of Nutrition . 130 . 7 . 1653–6 . July 2000 . 10867031 . 10.1093/jn/130.7.1653 .
  101. Blenis J, Resh MD . Subcellular localization specified by protein acylation and phosphorylation . Current Opinion in Cell Biology . 5 . 6 . 984–989 . December 1993 . 8129952 . 10.1016/0955-0674(93)90081-Z .
  102. Vermeer C . Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase . The Biochemical Journal . 266 . 3 . 625–636 . March 1990 . 2183788 . 1131186 . 10.1042/bj2660625 .
  103. Bhattacharjee A, Bansal M . Collagen structure: the Madras triple helix and the current scenario . IUBMB Life . 57 . 3 . 161–172 . March 2005 . 16036578 . 10.1080/15216540500090710 . 7211864 .
  104. Park MH . The post-translational synthesis of a polyamine-derived amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF5A) . Journal of Biochemistry . 139 . 2 . 161–169 . February 2006 . 16452303 . 2494880 . 10.1093/jb/mvj034 .
  105. Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, Cynober L . Almost all about citrulline in mammals . Amino Acids . 29 . 3 . 177–205 . November 2005 . 177 . 16082501 . 10.1007/s00726-005-0235-4 . 23877884 .
  106. Coxon KM, Chakauya E, Ottenhof HH, Whitney HM, Blundell TL, Abell C, Smith AG . Pantothenate biosynthesis in higher plants . Biochemical Society Transactions . 33 . Pt 4 . 743–746 . August 2005 . 16042590 . 10.1042/BST0330743 .
  107. Hylin JW . 1969 . Toxic peptides and amino acids in foods and feeds . Journal of Agricultural and Food Chemistry . 17 . 3 . 492–496 . 10.1021/jf60163a003. 1969JAFC...17..492H .
  108. Savelieva KV, Zhao S, Pogorelov VM, Rajan I, Yang Q, Cullinan E, Lanthorn TH . Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants . PLOS ONE . 3 . 10 . e3301 . 2008 . 18923670 . 2565062 . 10.1371/journal.pone.0003301 . Bartolomucci A . free . 2008PLoSO...3.3301S .
  109. Höglund E, Øverli Ø, Winberg S . Tryptophan Metabolic Pathways and Brain Serotonergic Activity: A Comparative Review . Frontiers in Endocrinology . 10 . 158 . 2019 . 31024440 . 6463810 . 10.3389/fendo.2019.00158 . free .
  110. Fernstrom JD, Fernstrom MH . Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain . The Journal of Nutrition . 137 . 6 Suppl 1 . 1539S–1547S; discussion 1548S . June 2007 . 17513421 . 10.1093/jn/137.6.1539S .
  111. Book: Kuhar MJ, Couceyro PR, Lambert PD . Biosynthesis of Catecholamines. . Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD . Basic Neurochemistry: Molecular, Cellular and Medical Aspects. . 6th . Philadelphia . Lippincott-Raven . 1999 .
  112. Matthews DE . An overview of phenylalanine and tyrosine kinetics in humans . The Journal of Nutrition . 137 . 6 Suppl 1 . 1549S–1555S; discussion 1573S–1575S . June 2007 . 17513423 . 2268015 . 10.1093/jn/137.6.1549S .
  113. Noel JP, Austin MB, Bomati EK . Structure-function relationships in plant phenylpropanoid biosynthesis . Current Opinion in Plant Biology . 8 . 3 . 249–53 . June 2005 . 15860421 . 2861907 . 10.1016/j.pbi.2005.03.013 . 2005COPB....8..249N .
  114. Shemin D, Rittenberg D . The biological utilization of glycine for the synthesis of the protoporphyrin of hemoglobin . The Journal of Biological Chemistry . 166 . 2 . 621–625 . December 1946 . 20276176 . 10.1016/S0021-9258(17)35200-6 . free .
  115. Tejero J, Biswas A, Wang ZQ, Page RC, Haque MM, Hemann C, Zweier JL, Misra S, Stuehr DJ . Stabilization and characterization of a heme-oxy reaction intermediate in inducible nitric-oxide synthase . The Journal of Biological Chemistry . 283 . 48 . 33498–33507 . November 2008 . 18815130 . 2586280 . 10.1074/jbc.M806122200 . free .
  116. Rodríguez-Caso C, Montañez R, Cascante M, Sánchez-Jiménez F, Medina MA . Mathematical modeling of polyamine metabolism in mammals . The Journal of Biological Chemistry . 281 . 31 . 21799–21812 . August 2006 . 16709566 . 10.1074/jbc.M602756200 . free . free . 2006JBiCh.28121799R . 10630/32289 .
  117. Book: Stryer L, Berg JM, Tymoczko JL . Biochemistry . registration . 2002 . W.H. Freeman . New York . 978-0-7167-4684-3 . 5th . 693–698.
  118. Longo N, Frigeni M, Pasquali M . Carnitine transport and fatty acid oxidation . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1863 . 10 . 2422–35 . October 2016 . 26828774 . 4967041 . 10.1016/j.bbamcr.2016.01.023 .
  119. Sharma S, Black SM . CCarnitine Homeostasis, Mitochondrial Function, and Cardiovascular Disease . Drug Discovery Today: Disease Mechanisms . 6 . 1–4 . e31–e39 . 2009 . 20648231 . 2905823 . 10.1016/j.ddmec.2009.02.001 .
  120. Petroff OA . GABA and glutamate in the human brain . The Neuroscientist . 8 . 6 . 562–573 . December 2002 . 12467378 . 10.1177/1073858402238515 . 84891972 .
  121. Turner EH, Loftis JM, Blackwell AD . Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan . Pharmacology & Therapeutics . 109 . 3 . 325–338 . March 2006 . 16023217 . 10.1016/j.pharmthera.2005.06.004 . 2563606 .
  122. Kostrzewa RM, Nowak P, Kostrzewa JP, Kostrzewa RA, Brus R . Peculiarities of L: -DOPA treatment of Parkinson's disease . Amino Acids . 28 . 2 . 157–164 . March 2005 . 15750845 . 10.1007/s00726-005-0162-4 . 33603501 .
  123. Heby O, Persson L, Rentala M . Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas' disease, and leishmaniasis . Amino Acids . 33 . 2 . 359–366 . August 2007 . 17610127 . 10.1007/s00726-007-0537-9 . 26273053 .
  124. Rosenthal GA . L-Canavanine: a higher plant insecticidal allelochemical . Amino Acids . 21 . 3 . 319–330 . 2001 . 11764412 . 10.1007/s007260170017 . 3144019 .
  125. Hammond AC . Leucaena toxicosis and its control in ruminants . Journal of Animal Science . 73 . 5 . 1487–1492 . May 1995 . 7665380 . 10.2527/1995.7351487x . 1995JAniS..73.1487H .
  126. Ter Meulen U, Struck S, Schulke E, El Harith EA . A review on the nutritive value and toxic aspects of Leucaena leucocephala. . Tropical Animal Health and Production . 1979 . 4 . 2 . 113–126 .
  127. Walsh CT, O'Brien RV, Khosla C . Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds . Angewandte Chemie (International ed. In English) . 52 . 28 . 7098–124 . July 2013 . 23729217 . 10.1002/anie.201208344 . 4634941 . 2013ACIE...52.7098W .
  128. Sakami W, Harrington H . Amino Acid Metabolism . Annual Review of Biochemistry . 32 . 1 . 355–398 . 1963 . 14144484 . 10.1146/annurev.bi.32.070163.002035 . 1963ARBio..32..355S .
  129. Brosnan JT . Glutamate, at the interface between amino acid and carbohydrate metabolism . The Journal of Nutrition . 130 . 4S Suppl . 988S–990S . April 2000 . 10736367 . 10.1093/jn/130.4.988S . free .
  130. Young VR, Ajami AM . Glutamine: the emperor or his clothes? . The Journal of Nutrition . 131 . 9 Suppl . 2449S–2459S, 2486S–2487S . September 2001 . 11533293 . 10.1093/jn/131.9.2449S . free .
  131. Young VR . Adult amino acid requirements: the case for a major revision in current recommendations . The Journal of Nutrition . 124 . 8 Suppl . 1517S–1523S . August 1994 . 8064412 . 10.1093/jn/124.suppl_8.1517S . free .
  132. Fürst P, Stehle P . What are the essential elements needed for the determination of amino acid requirements in humans? . The Journal of Nutrition . 134 . 6 Suppl . 1558S–1565S . June 2004 . 15173430 . 10.1093/jn/134.6.1558S . free .
  133. Reeds PJ . Dispensable and indispensable amino acids for humans . The Journal of Nutrition . 130 . 7 . 1835S–1840S . July 2000 . 10867060 . 10.1093/jn/130.7.1835S . free .
  134. Imura K, Okada A . Amino acid metabolism in pediatric patients . Nutrition . 14 . 1 . 143–148 . January 1998 . 9437700 . 10.1016/S0899-9007(97)00230-X .
  135. Lourenço R, Camilo ME . Taurine: a conditionally essential amino acid in humans? An overview in health and disease . Nutricion Hospitalaria . 17 . 6 . 262–270 . 2002 . 12514918 .
  136. Leuchtenberger W, Huthmacher K, Drauz K . Biotechnological production of amino acids and derivatives: current status and prospects . Applied Microbiology and Biotechnology . 69 . 1 . 1–8 . November 2005 . 16195792 . 10.1007/s00253-005-0155-y . 24161808 .
  137. Book: Ashmead HE . The Role of Amino Acid Chelates in Animal Nutrition. 1993. Noyes Publications. Westwood.
  138. Garattini S . Glutamic acid, twenty years later . The Journal of Nutrition . 130 . 4S Suppl . 901S–909S . April 2000 . 10736350 . 10.1093/jn/130.4.901S . free .
  139. Stegink LD . The aspartame story: a model for the clinical testing of a food additive . The American Journal of Clinical Nutrition . 46 . 1 Suppl . 204–215 . July 1987 . 3300262 . 10.1093/ajcn/46.1.204 .
  140. Hanessian S . 1993 . Reflections on the total synthesis of natural products: Art, craft, logic, and the chiron approach . Pure and Applied Chemistry . 65 . 6 . 1189–1204 . 10.1351/pac199365061189 . 43992655 . free .
  141. Blaser HU . 1992 . The chiral pool as a source of enantioselective catalysts and auxiliaries . Chemical Reviews . 92 . 5 . 935–952 . 10.1021/cr00013a009.
  142. Book: Ashmead HE . Foliar Feeding of Plants with Amino Acid Chelates. 1986. Noyes Publications. Park Ridge.
  143. Sanda F, Endo T . 1999 . Syntheses and functions of polymers based on amino acids . Macromolecular Chemistry and Physics . 200 . 12 . 2651–2661 . 10.1002/(SICI)1521-3935(19991201)200:12<2651::AID-MACP2651>3.0.CO;2-P . free .
  144. Gross RA, Kalra B . Biodegradable polymers for the environment . Science . 297 . 5582 . 803–807 . August 2002 . 12161646 . 10.1126/science.297.5582.803 . 12 June 2019 . live . 2002Sci...297..803G . https://web.archive.org/web/20200725075829/https://zenodo.org/record/1231185 . 25 July 2020 .
  145. Book: Commercial poly(aspartic acid) and Its Uses . Low KC, Wheeler AP, Koskan LP . Advances in Chemistry Series . 248 . . Washington, D.C. . 1996.
  146. Thombre SM, Sarwade BD . 2005 . Synthesis and Biodegradability of Polyaspartic Acid: A Critical Review . Journal of Macromolecular Science, Part A . 42 . 9 . 1299–1315 . 10.1080/10601320500189604. 94818855 .
  147. Book: Jones RC, Buchanan BB, Gruissem W . Biochemistry & molecular biology of plants . American Society of Plant Physiologists . Rockville, Md . 2000 . 371–372 . 978-0-943088-39-6 .
  148. Koper K, Han SW, Pastor DC, Yoshikuni Y, Maeda HA . Evolutionary origin and functional diversification of aminotransferases . The Journal of Biological Chemistry . 298 . 8 . 102122 . August 2022 . 35697072 . 9309667 . 10.1016/j.jbc.2022.102122 . free .
  149. Koper K, Han SW, Kothadia R, Salamon H, Yoshikuni Y, Maeda HA . Multisubstrate specificity shaped the complex evolution of the aminotransferase family across the tree of life . Proceedings of the National Academy of Sciences of the United States of America . 121 . 26 . e2405524121 . June 2024 . 38885378 . 11214133 . 10.1073/pnas.2405524121 . free . 2024PNAS..12105524K .
  150. Brosnan JT, Brosnan ME . The sulfur-containing amino acids: an overview . The Journal of Nutrition . 136 . 6 Suppl . 1636S–1640S . June 2006 . 16702333 . 10.1093/jn/136.6.1636S . free .
  151. Book: Kivirikko KI, Pihlajaniemi T . Collagen Hydroxylases and the Protein Disulfide Isomerase Subunit of Prolyl 4-Hydroxylases . Advances in Enzymology and Related Areas of Molecular Biology . 72 . 325–398 . 1998 . 9559057 . 10.1002/9780470123188.ch9 . 978-0-470-12318-8 . Advances in Enzymology – and Related Areas of Molecular Biology .
  152. Whitmore L, Wallace BA . Analysis of peptaibol sequence composition: implications for in vivo synthesis and channel formation . European Biophysics Journal . 33 . 3 . 233–237 . May 2004 . 14534753 . 10.1007/s00249-003-0348-1 . 24638475 .
  153. Alexander L, Grierson D . Ethylene biosynthesis and action in tomato: a model for climacteric fruit ripening . Journal of Experimental Botany . 53 . 377 . 2039–2055 . October 2002 . 12324528 . 10.1093/jxb/erf072 . free .
  154. Danchin A . From chemical metabolism to life: the origin of the genetic coding process . Beilstein Journal of Organic Chemistry . 13 . 1 . 1119–1135 . 12 June 2017 . 28684991 . 5480338 . 10.3762/bjoc.13.111 .
  155. Encyclopedia: Pascal R, Boiteau L . Origins of Life: Emergence of Amino Acids . Wiley Encyclopedia of Chemical Biology . December 2007 . 1–7 . 10.1002/9780470048672.wecb423 . 978-0-471-75477-0 .
  156. Frenkel-Pinter M, Samanta M, Ashkenasy G, Leman LJ . Prebiotic Peptides: Molecular Hubs in the Origin of Life . Chemical Reviews . 120 . 11 . 4707–4765 . June 2020 . 32101414 . 10.1021/acs.chemrev.9b00664 . 211536416 . 2020ChRv..120.4707F .
  157. 10.1016/j.gsf.2017.07.007 . Origins of building blocks of life: A review . 2018 . Kitadai N, Maruyama S . Geoscience Frontiers . 9 . 4 . 1117–1153 . 2018GeoFr...9.1117K . 102659869 . free .
  158. Milner-White EJ . Protein three-dimensional structures at the origin of life . Interface Focus . 9 . 6 . 20190057 . December 2019 . 31641431 . 6802138 . 10.1098/rsfs.2019.0057 .
  159. Chatterjee S, Yadav S . The Coevolution of Biomolecules and Prebiotic Information Systems in the Origin of Life: A Visualization Model for Assembling the First Gene . Life . 12 . 6 . 834 . June 2022 . 35743865 . 9225589 . 10.3390/life12060834 . free . 2022Life...12..834C .
  160. Kirschning A . The coenzyme/protein pair and the molecular evolution of life . Natural Product Reports . 38 . 5 . 993–1010 . May 2021 . 33206101 . 10.1039/D0NP00037J . 227037164 . free .
  161. Book: Elmore DT, Barrett GC . Amino acids and peptides . limited . Cambridge University Press . Cambridge, UK . 1998 . 48–60 . 978-0-521-46827-5.
  162. Gutteridge A, Thornton JM . Understanding nature's catalytic toolkit . Trends in Biochemical Sciences . 30 . 11 . 622–629 . November 2005 . 16214343 . 10.1016/j.tibs.2005.09.006 .
  163. Ibba M, Söll D . The renaissance of aminoacyl-tRNA synthesis . EMBO Reports . 2 . 5 . 382–387 . May 2001 . 11375928 . 1083889 . 10.1093/embo-reports/kve095 .
  164. Lengyel P, Söll D . Mechanism of protein biosynthesis . Bacteriological Reviews . 33 . 2 . 264–301 . June 1969 . 4896351 . 378322 . 10.1128/MMBR.33.2.264-301.1969 .
  165. Book: Jakubowski H, Flatt P . 26.2: Protein Synthesis . 2025 . Fundamentals of Biochemistry. Vol. III – Information Pathways . Biology LibreTexts . 2025-12-09.
  166. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND . Glutathione metabolism and its implications for health . The Journal of Nutrition . 134 . 3 . 489–492 . March 2004 . 14988435 . 10.1093/jn/134.3.489 . free .
  167. Meister A . Glutathione metabolism and its selective modification . The Journal of Biological Chemistry . 263 . 33 . 17205–17208 . November 1988 . 3053703 . 10.1016/S0021-9258(19)77815-6 . free .
  168. Carpino LA . 1992 . 1-Hydroxy-7-azabenzotriazole. An efficient peptide coupling additive . Journal of the American Chemical Society . 115 . 10 . 4397–4398 . 10.1021/ja00063a082.
  169. Marasco D, Perretta G, Sabatella M, Ruvo M . Past and future perspectives of synthetic peptide libraries . Current Protein & Peptide Science . 9 . 5 . 447–467 . October 2008 . 18855697 . 10.2174/138920308785915209 .
  170. Konara S, Gagnona K, Clearfield A, Thompson C, Hartle J, Ericson C, Nelson C . Structural determination and characterization of copper and zinc bis-glycinates with X-ray crystallography and mass spectrometry . Journal of Coordination Chemistry . 2010 . 63 . 19 . 10.1080/00958972.2010.514336 . 3335–3347 . 94822047.
  171. Knorre DG, Kudryashova NV, Godovikova TS . Chemical and functional aspects of posttranslational modification of proteins . Acta Naturae . 1 . 3 . 29–51 . October 2009 . 22649613 . 10.32607/20758251-2009-1-3-29-51. 3347534 .
  172. Keenan EK, Zachman DK, Hirschey MD . Discovering the landscape of protein modifications . Molecular Cell . 81 . 9 . 1868–1878 . May 2021 . 33798408 . 10.1016/j.molcel.2021.03.015 . 8106652 .
  173. Schofield LC, Dialpuri JS, Murshudov GN, Agirre J . Post-translational modifications in the Protein Data Bank . Acta Crystallographica Section D . 80 . Pt 9 . 647–660 . September 2024 . 39207896 . 11394121 . 10.1107/S2059798324007794 . 2024AcCrD..80..647S .
  174. Book: Brosnan ME, Brosnan JT . Basicmedical Key . BasicMedicalKey.com . 2017 . Chapter 14: Amino Acid Metabolism . 23 December 2025 .
  175. Chandel NS . Amino Acid Metabolism . Cold Spring Harbor Perspectives in Biology . 13 . 4 . a040584. April 2021 . 33795250 . 8015690 . 10.1101/cshperspect.a040584 .
  176. Dghaym RD, Dhawan R, Arndtsen BA . The Use of Carbon Monoxide and Imines as Peptide Derivative Synthons: A Facile Palladium-Catalyzed Synthesis of α-Amino Acid Derived Imidazolines . Angewandte Chemie . 40 . 17 . 3228–3230 . September 2001 . 29712039 . 10.1002/(SICI)1521-3773(19980703)37:12<1634::AID-ANIE1634>3.0.CO;2-C .
  177. Muñoz-Huerta RF, Guevara-Gonzalez RG, Contreras-Medina LM, Torres-Pacheco I, Prado-Olivarez J, Ocampo-Velazquez RV . A review of methods for sensing the nitrogen status in plants: advantages, disadvantages and recent advances . Sensors . 13 . 8 . 10823–10843 . August 2013 . 23959242 . 3812630 . 10.3390/s130810823 . free . 2013Senso..1310823M .
  178. Martin PD, Malley DF, Manning G, Fuller L . 2002 . Determination of soil organic carbon and nitrogen at thefield level using near-infrared spectroscopy . Canadian Journal of Soil Science . 82 . 4 . 413–422 . 10.4141/S01-054 . 2002CaJSS..82..413M .

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