amino acid amino acid amino acids are organic compounds that contain both amino and carboxylic acid functional groups. although over 500 amino acids exist in nature, by far the most important are the alpha-amino acids, from which proteins are composed. only 22 alpha amino acids appear in the genetic code. structure of a generic l-alpha-amino acid in the "neutral" form needed for defining a systematic name, without implying that this form actually exists in detectable amounts either in aqueous solution or in the solid state. amino acids can be classified according to the locations of the core structural functional groups, as alpha- (α-), beta- (β-), gamma- (γ-) or delta- (δ-) amino acids; other categories relate to polarity, ionization, and side chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or sulfur, etc.). in the form of proteins, amino acid residues form the second-largest component (water being the largest) of human muscles and other tissues. 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. 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 ch3−ch(nh2)−cooh. the commission justified this approach as follows: 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. 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. cystine was discovered in 1810, although its monomer, cysteine, remained undiscovered until 1884. glycine and leucine were discovered in 1820. 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. the unity of the chemical category was recognized by wurtz in 1865, but he gave no particular name to it. the first use of the term "amino acid" in the english language dates from 1898, while the german term, aminosäure, was used earlier. 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". general structure the 21 proteinogenic α-amino acids found in eukaryotes, grouped according to their side chains' pka values and charges carried at physiological ph (7.4) in the structure shown at the top of the page, r represents a side chain specific to each amino acid. the carbon atom next to the carboxyl group is called the α–carbon. amino acids containing an amino group bonded directly to the α-carbon are referred to as α-amino acids. these include proline and hydroxyproline, which are secondary amines. in the past they were often called imino acids, a misnomer because they do not contain an imine grouping hn=c. isomerism the common natural forms of amino acids have a zwitterionic structure, with −nh+3 (−nh+2− in the case of proline) and −co−2 functional groups attached to the same c atom, and are thus α-amino acids. with the exception of achiral glycine, natural amino acids have the l configuration, and are the only ones found in proteins during translation in the ribosome. the l and d convention for amino acid configuration refers not to the optical activity of the amino acid itself but rather to the optical activity of the isomer of glyceraldehyde from which that amino acid can, in theory, be synthesized (d-glyceraldehyde is dextrorotatory; l-glyceraldehyde is levorotatory). an alternative convention is to use the (s) and (r) designators to specify the absolute configuration. almost all of the amino acids in proteins are (s) at the α carbon, with cysteine being (r) and glycine non-chiral. cysteine has its side chain in the same geometric location as the other amino acids, but the r/s terminology is reversed because sulfur has higher atomic number compared to the carboxyl oxygen which gives the side chain a higher priority by the cahn-ingold-prelog sequence rules, whereas the atoms in most other side chains give them lower priority compared to the carboxyl group. rarely, d-amino acid residues are found in proteins, and are converted from the l-amino acid as a post-translational modification. side chains amino acids are designated as α- when the amino nitrogen atom is attached to the α-carbon, the carbon atom adjacent to the carboxylate group. there are several ways to classify amino acids; however, they are often grouped by the polarity of their side chains, as depicted in the graphic at the head of this section. charged side chains 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. many proteins bind metal into their structures specifically, and these interactions are commonly mediated by charged side chains such as aspartate, glutamate and histidine. 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. functional groups found in histidine (left), lysine (middle) and arginine (right) 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 side chains 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, though 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. hydrophobic side chains 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, with the exception of tyrosine (tyr, y). the hydroxyl of tyrosine can deprotonate at high ph forming the negatively charged phenolate. because of this one could place tyrosine into the polar, uncharged amino acid category, but its very low solubility in water matches the characteristics of hydrophobic amino acids well. special case side chains 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 with other cysteines called disulphide bonds. 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. pyrrolysine (pyl, o) is another amino acid not encoded in dna, but synthesized into protein by ribosomes. it is found in archaeal species where it participates in the catalytic activity of several methyltransferases. β- and γ-amino acids amino acids with the structure nh+3−cxy−cxy−co−2, such as β-alanine, a component of carnosine and a few other peptides, are β-amino acids. ones with the structure nh+3−cxy−cxy−cxy−co−2 are γ-amino acids, and so on, where x and y are two substituents (one of which is normally h). zwitterions ionization and brønsted character of n-terminal amino, c-terminal carboxylate, and side chains of amino acid residues in aqueous solution at ph close to neutrality, amino acids exist as zwitterions, i.e. as dipolar ions with both nh+3 and co−2 in charged states, so the overall structure is nh+3−chr−co−2. at physiological ph the so-called "neutral forms" −nh2−chr−co2h are not present to any measurable degree. although the two charges in the zwitterion structure add up to zero it is misleading to call a species with a net charge of zero "uncharged". in strongly acidic conditions (ph below 3), the carboxylate group becomes protonated and the structure becomes an ammonio carboxylic acid, nh+3−chr−co2h. 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. in highly basic conditions (ph greater than 10, not normally seen in physiological conditions), the ammonio group is deprotonated to give nh2−chr−co−2. 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: 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. isoelectric point composite of titration curves of twenty proteinogenic amino acids grouped by side chain category 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. this ph is known as the isoelectric point pi, so pi = 1/2(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 −nh+3, 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 = 1/2(pka1 + pka(r)), where pka(r) is the side chain pka. 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,