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 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life.
Amino acids can be classified according to the locations of the core structural functional groups , beta- , gamma- ; other categories relate to polarity, ionization, and side-chain group type. In the form of proteins, amino-acid residues form the second-largest component 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. 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".

Structure

α-amino acids

2-, alpha-, or α-amino acids have the generic formula in most cases, where R is an organic substituent known as a "side chain".
Of the many hundreds of described amino acids, 22 are proteinogenic. It is these 22 compounds that combine to give a vast array of peptides and proteins assembled by ribosomes. Non-proteinogenic amino acids may arise through nonribosomal peptide synthesis. Modified amino acids, by contrast, typically result from post-translational modification.

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.

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 have been found in nature, e.g., in bacterial envelopes, as a neuromodulator, and in some antibiotics. Rarely, D-amino acid residues are found in proteins, and are converted from the L-amino acid as a post-translational modification.

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. 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.
The two negatively charged amino acids at neutral pH are aspartate and glutamate. 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.
There are three amino acids with side chains that are cations at neutral pH: arginine, lysine and histidine. 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 pK_a 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, threonine, asparagine and glutamine 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 chiral center at the α-carbon shared by all amino acids apart from achiral glycine, but also at the β-carbon. The full stereochemical specification is -L-threonine.
Because of the presence of phenolic hydroxyl group with a pK_a = ~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.

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 pK_as.

Classification outliers

Several side chains are not described well by the charged, polar and hydrophobic categories. Glycine 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 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 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 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 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.

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 buried in the middle of the protein, whereas hydrophilic side chains are exposed to the aqueous solvent. 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. There are various hydrophobicity scales of amino acid residues.
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.
Many proteins undergo a range of posttranslational modifications, whereby additional chemical groups are attached to the amino acid residue side chains sometimes producing lipoproteins, or glycoproteins 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.