8 Amino Acids

[Ray Kowalewski]

Nonessential means that our bodies can produce the amino acid, even if we do not get it from the food we eat. Nonessential amino acids include: alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine.

You do not need to eat essential and nonessential amino acids at every meal, but getting a balance of them over the whole day is important. A diet based on a single plant item will not be adequate, but we no longer worry about pairing proteins (such as beans with rice) at a single meal. Instead we look at the adequacy of the diet overall throughout the day.

Updated by: Stefania Manetti, RD/N, CDCES, RYT200, My Vita Sana LLC - Nourish and heal through food, San Jose, CA. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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.

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.

The first few amino acids were discovered in the early 1800s.[7][8] 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.[9][10] Cystine was discovered in 1810,[11] although its monomer, cysteine, remained undiscovered until 1884.[12][10][a] Glycine and leucine were discovered in 1820.[13] 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.[14][15]

The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it.[16] The first use of the term "amino acid" in the English language dates from 1898,[17] while the German term, Aminosure, was used earlier.[18] 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".[19]

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

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.[26][27] Rarely, D-amino acid residues are found in proteins, and are converted from the L-amino acid as a post-translational modification.[28][c]

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.[31] 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.[32]

The two negatively charged amino acids at neutral pH are aspartate (Asp, D) and glutamate (Glu, E). The anionic carboxylate groups behave as Brnsted bases in most circumstances.[31] Enzymes in very low pH environments, like the aspartic protease pepsin in mammalian stomachs, may have catalytic aspartate or glutamate residues that act as Brnsted acids.

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.[31]

Nonpolar amino acid interactions are the primary driving force behind the processes that fold proteins into their functional three dimensional structures.[31] 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.

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.[31] 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.[33] Pyrrolysine (Pyl, O) is another amino acid not encoded in DNA, but synthesized into protein by ribosomes.[34] It is found in archaeal species where it participates in the catalytic activity of several methyltransferases.

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 Brnsted:[36][37] 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 Brnsted bases in proteins. Likewise, lysine, tyrosine and cysteine will typically act as a Brnsted acid. Histidine under these conditions can act both as a Brnsted acid and a base.

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. Zwitterions have minimum solubility at their isoelectric point, and some amino acids (in particular, with nonpolar side chains) can be isolated by precipitation from water by adjusting the pH to the required isoelectric point.

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.

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.[39][41][42]

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),[43] or glycoproteins (that are hydrophilic)[44] 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.[45]

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.[55][56]

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