A polypeptide is an unbranched chain of amino acids.

Amino acids ( /mino/, /mano/, or /mno/) are biologically important molecules made from amine (-NH2) and carboxylic acid (-COOH) functional groups, along with a side-chain specific to each amino acid. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen. About 500 amino acids are known[1] which can be classified in many ways. Structurally they can be classified according to the functional groups' locations as alpha- (-), beta- (-), gamma- (-) or delta- (-) amino acids; other categories relate to polarity, acid/base/neutral, and side chain group type (including: aliphatic, acyclic, hydroxyl or sulphur-containing, aromatic). In the form of proteins, amino acids comprise the second largest component other than water of human muscles, cells and other tissues.[2] Outside proteins, amino acids also perform critical biological roles including neurotransmitters, transport, and in synthesis. Amino acids having both the amine and carboxylic acid groups attached to the first, or alpha, carbon atom have particular importance in biochemistry. They are known as 2-, alpha-, or -amino acids (generic formula H2NCHRCOOH in most cases[3] where R is an organic substituent known as a "side-chain");[4] often the term "amino acid" is used to refer specifically to these. They include the 22 proteinogenic ("protein building") amino acids which combine into peptide chains ("polypeptides") to form the building blocks of a vast array of proteins.[5] These are all L-stereoisomers (left handed isomers) although a few D-amino acids (right handed) occur in bacterial envelopes and some antibiotics.[6][7] 20 of the 22 proteinogenic amino acids are known as "standard" amino acids-those found in human beings and other eukaryotes, and which are encoded directly within the universal genetic code. The 2 exceptions are the "non-standard" or "non-canonical" pyrrolysine found only in some methanogenic organisms but not humans and selenocysteine; both of these are encoded via variant codons signaled by mRNA instead.[8][9][10] CodontRNA combinations not found in nature can also be used to "expand" the genetic code and create novel proteins known as "alloproteins" incorporating non-proteinogenic amino acids.[11][12][13] Many important proteinogenic and non-proteinogenic amino acids also play critical non-protein roles within the body. For example the standard glutamic acid (glutamate) and the non-standard gamma-amino acid gamma-amino-butyric acid (GABA) are respectively the brain's main excitatory and inhibitory neurotransmitters,[14] hydroxyproline-a major component of the connective tissue collagen-is synthesised from proline, the standard amino acid glycine is used to synthesise porphyrins used in red blood cells, and the non-standard carnitine is used in lipid transport. 9 of the 20 standard amino acids are called "essential" amino acids for humans because they cannot be created from other compounds by the human body, and so must be taken in as food. Others may be conditionally essential for some ages or medical conditions. Essential amino acids may also differ between species.[15]

Because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements, fertilizers, and food technology. Industrial uses include the production of biodegradable plastics, drugs, and chiral catalysts.

History

The first few amino acids were discovered in the early 19th century. In 1806, the French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus that was subsequently named asparagine, the first amino acid to be discovered.[16][17] Another amino acid that was discovered in the early 19th century was cystine, in 1810,[18] although its monomer, cysteine, was discovered much later, in 1884.[17][19] Glycine and leucine were also discovered around this time, in 1820.[20] Usage of the term amino acid in the English language is from 1898.[21] Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister proposed that proteins are the result of the formation of bonds between the amino group of one amino acid with the carboxyl group of another in a linear structure which Fischer termed peptide.[22] General structure Lysine with the carbon atoms in the side-chain labeled 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 carbon and amino acids with a side-chain bonded to this carbon are referred to as alpha amino acids. These are the most common form found in nature. In the alpha amino acids, the carbon is a chiral carbon atom, with the exception of glycine.[23] In amino acids that have a carbon chain attached to the carbon (such as lysine, shown to the right) the carbons are labeled in order as , , , , and so on.[24] In some amino acids, the amine group is attached to the or -carbon, and these are therefore referred to as beta or gamma amino acids. Amino acids are usually classified by the properties of their side-chain into four groups. The side-chain can make an amino acid a weak acid or a weak base, and a hydrophile if the side-chain is polar or a hydrophobe if it is nonpolar.[23] The chemical structures of the 22 standard amino acids, along with their chemical properties, are described more fully in the article on these proteinogenic amino acids. The phrase "branched-chain amino acids" or BCAA refers to the amino acids having aliphatic side-chains that are non-linear; these are leucine, isoleucine, and valine. Proline is the only proteinogenic amino acid whose side-group links to the -amino group and, thus, is also the only proteinogenic amino acid containing a secondary amine at this position. [23] In chemical terms, proline is, therefore, an imino acid, since it lacks a primary amino group,[25] although it is still classed as an amino acid in the current biochemical nomenclature,[26] and may also be called an "N-alkylated alpha-amino acid".[27] The two enantiomers of alanine, D-Alanine and L-Alanine
Isomerism

A polypeptide is an unbranched chain of amino acids.

Of the standard -amino acids, all but glycine can exist in either of two enantiomers, called L or D amino acids, which are mirror images of each other (see also Chirality). While L-amino acids represent all of the amino acids found in proteins during translation in the ribosome, Damino acids are found in some proteins produced by enzyme posttranslational modifications after translation and translocation to the endoplasmic reticulum, as in exotic sea-dwelling organisms such as cone snails.[28] They are also abundant components of the peptidoglycan cell walls of bacteria,[29] and D-serine may act as a neurotransmitter in the brain.[30] 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 dextrorotary; L-glyceraldehyde is levorotatory). In alternative fashion, the (S) and (R) designators are used to indicate the absolute stereochemistry. Almost all of the amino acids in proteins are (S) at the carbon, with cysteine being (R) and glycine non-chiral.[31] Cysteine is unusual since it has a sulfur atom at the second position in its side-chain, which has a larger atomic mass than the groups attached to the first carbon, which is attached to the -carbon in the other standard amino acids, thus the (R) instead f (S). An amino acid in its (1) un-ionized and (2) zwitterionic forms
Zwitterions

The amine and carboxylic acid functional groups found in amino acids allow them to have amphiprotic properties.[23] Carboxylic acid groups (CO2H) can be deprotonated to become negative carboxylates (CO2 ), and -amino groups (NH2) can be protonated to become positive -ammonium groups (+NH3). At pH values greater than the pKa of the carboxylic acid group (mean for the 20 common amino acids is about 2.2, see the table of amino acid structures above), the negative carboxylate ion predominates. At pH values lower than the pKa of the -ammonium group (mean for the 20 common -amino acids is about 9.4), the nitrogen is predominantly protonated as a positively charged -ammonium group. Thus, at pH between 2.2 and 9.4, the predominant form adopted by -amino acids contains a negative carboxylate and a positive -ammonium group, as shown in structure (2) on the right, so has net zero charge. This molecular state is known as a zwitterion, from the German Zwitter meaning hermaphrodite or hybrid.[32] Below pH 2.2, the predominant form will have a neutral carboxylic acid group and a positive -ammonium ion (net charge +1), and above pH 9.4, a negative carboxylate and neutral -amino group (net charge 1). The fully neutral form (structure (1) on the right) is a very minor species in aqueous solution throughout the pH range (less than 1 part in 107). Amino acids also exist as zwitterions in the solid phase, and crystallize with salt-like properties unlike typical organic acids or amines.
Isoelectric point

At pH values between the two pKa values, the zwitterion predominates, but coexists in dynamic equilibrium with small amounts of net negative and net positive ions. At the exact midpoint between the two pKa values, the trace amount of net negative and trace of net positive ions exactly balance, so that average net charge of all forms present is zero. [33] This pH is known as the isoelectric point pI, so pI = (pKa1 + pKa2). The individual amino acids all have slightly different pKa values, so have different isoelectric points. For amino acids with charged side-chains, the pKa of the side-chain is involved. Thus for Asp, Glu with negative side-chains, pI = (pKa1 + pKaR), where pKaR is the side-chain pKa. Cysteine also has potentially negative side-chain with pKaR = 8.14, so pI should be calculated as for Asp and Glu, even though the side-chain is not significantly charged at neutral pH. For His, Lys, and Arg with positive side-chains, pI = (pKaR + pKa2). 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 isolectric point and some amino acids (in particular, with non-polar side-chains) can be isolated by precipitation from water by adjusting the pH to the required isoelectric point.
Occurrence and functions in biochemistry

A polypeptide is an unbranched chain of amino acids.

Standard amino acids

Amino acids are the structural units that make up proteins. They join together to form short polymer chains called peptides or longer chains called either polypeptides or proteins. These polymers are linear and unbranched, with each amino acid within the chain attached to two neighboring amino acids. The process of making proteins 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.[34] The order in which the amino acids are added is read through the genetic code from an mRNA template, which is a RNA copy of one of the organism's genes. Twenty-two amino acids are naturally incorporated into polypeptides and are called proteinogenic or natural amino acids.[23] 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.[35] 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. [36] This UAG codon is followed by a PYLIS downstream sequence.[37]

The amino acid selenocysteine

Non-standard amino acids

A polypeptide is an unbranched chain of amino acids.

Aside from the 22 standard amino acids, there are many other amino acids that are called non-proteinogenic or non-standard. Those either are not found in proteins (for example carnitine, GABA), or are not produced directly and in isolation by standard cellular machinery (for example, hydroxyproline and selenomethionine). Non-standard amino acids that are found in proteins are formed by post-translational modification, which is modification after translation during protein synthesis. These modifications are often essential for the function or regulation of a protein; for example, the carboxylation of glutamate allows for better binding of calcium cations,[38] and the hydroxylation of proline is critical for maintaining connective tissues.[39] Another example is the formation of hypusine in the translation initiation factor EIF5A, through modification of a lysine residue.[40] 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.[41]

-alanine and its -alanine isomer Some nonstandard amino acids are not found in proteins. Examples include lanthionine, 2-aminoisobutyric acid, dehydroalanine, and the neurotransmitter gamma-aminobutyric acid. Nonstandard 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).[42] A rare exception to the dominance of -amino acids in biology is the -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.[43]
In human nutrition

When taken up into the human body from the diet, the 22 standard amino acids either are used to synthesize proteins and other biomolecules or are oxidized to urea and carbon dioxide as a source of energy.[44] 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.[45] Glucogenic amino acids can also be converted into glucose, through gluconeogenesis.[46] Pyrrolysine trait is restricted to several microbes, and only one organism has both Pyl and Sec. Of the 22 standard amino acids, 9 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.[47] In addition, cysteine, taurine, tyrosine, and arginine are semiessential amino-acids in children, because the metabolic pathways that synthesize these amino acids are not fully developed.[48][49] The amounts required also depend on the age and health of the individual, so it is hard to make general statements about the dietary requirement for some amino acids. Essential Histidine Isoleucine Leucine Lysine Methionine Threonine Tryptophan Valine Nonessential Alanine Arginine* Asparagine Aspartic acid Cysteine* Glutamine* Glycine Ornithine* Proline* Selenocysteine* Serine* Taurine* Tyrosine*
Non-protein functions

Phenylalanine Glutamic acid

In humans, non-protein amino acids also have important roles as metabolic intermediates, such as in the biosynthesis of the neurotransmitter gamma-aminobutyric acid. Many amino acids are used to synthesize other molecules, for example:

Tryptophan is a precursor of the neurotransmitter serotonin.[52]

A polypeptide is an unbranched chain of amino acids.

Tyrosine is a precursor of the catecholamine neurotransmitters dopamine, epinephrine and norepinephrine. Glycine is a precursor of porphyrins such as heme.[53] Arginine is a precursor of nitric oxide.[54] Ornithine and S-adenosylmethionine are precursors of polyamines.[55] Aspartate, glycine, and glutamine are precursors of nucleotides.[56] Phenylalanine is a precursor of various phenylpropanoids, which are important in plant metabolism.

However, not all of the functions of other abundant non-standard amino acids are known. For example, taurine is a major amino acid in muscle and brain tissues, but, although many functions have been proposed, its precise role in the body has not been determined.[57] Some non-standard amino acids are used as defenses against herbivores in plants.[58] For example canavanine is an analogue of arginine that is found in many legumes,[59] and in particularly large amounts in Canavalia gladiata (sword bean).[60] This amino acid protects the plants from predators such as insects and can cause illness in people if some types of legumes are eaten without processing. [61] The non-protein amino acid mimosine is found in other species of legume, particularly Leucaena leucocephala.[62] This compound is an analogue of tyrosine and can poison animals that graze on these plants.
Physicochemical properties of amino acids The 20 amino acids encoded directly by the genetic code can be divided into several groups based on their properties. Important factors are charge, hydrophilicity or hydrophobicity, size, and functional groups.[23] These properties are important for protein structure and proteinprotein interactions. The watersoluble 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. The integral membrane proteins tend to have outer rings of exposed hydrophobic amino acids that anchor them into the lipid bilayer. In the case part-way between these two extremes, some peripheral membrane proteins have a patch of hydrophobic amino acids on their surface that locks onto the membrane. In similar fashion, proteins that have to bind to positively-charged molecules have surfaces rich with negatively charged amino acids like glutamate and aspartate, while proteins binding to negatively-charged molecules have surfaces rich with positively charged chains like lysine and arginine. There are different hydrophobicity scales of amino acid residues.[102] Some amino acids have special properties such as cysteine, that can form covalent disulfide bonds to other cysteine residues, proline that forms a cycle to the polypeptide backbone, and glycine that is more flexible than other amino acids. Many proteins undergo a range of posttranslational modifications, when additional chemical groups are attached to the amino acids in proteins. Some modifications can produce hydrophobic lipoproteins,[103] or hydrophilic glycoproteins.[104] These type of modification allow the reversible targeting of a protein to a membrane. For example, the addition and removal of the fatty acid palmitic acid to cysteine residues in some signaling proteins causes the proteins to attach and then detach from cell membranes.[105]

Table of standard amino acid abbreviations and properties

Main article: Proteinogenic amino acid Amino Acid Alanine Arginine Asparagine Aspartic acid Cysteine Glutamic acid Glutamine Glycine Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Proline Serine Threonine Tryptophan Tyrosine Valine 3Letter[106] Ala Arg Asn Asp Cys Glu Gln Gly His Ile Leu Lys Met Phe Pro Ser Thr Trp Tyr Val 1Letter[106] A R N D C E Q G H I L K M F P S T W Y V Side-chain polarity[106] nonpolar polar polar polar nonpolar polar polar nonpolar polar neutral(90%) nonpolar nonpolar polar nonpolar nonpolar nonpolar polar polar nonpolar polar nonpolar neutral neutral positive neutral neutral neutral neutral neutral neutral neutral neutral 4.5 3.8 3.9 1.9 2.8 1.6 0.8 0.7 0.9 1.3 4.2 280, 219 274, 222, 193 5.6, 47.0 1.4, 8.0, 48.0 257, 206, 188 0.2, 9.3, 60.0 Side-chain charge (pH 7.4)[106] neutral positive neutral negative neutral negative neutral neutral positive(10%) 3.2 211 5.9 Hydropathy index[107] 1.8 4.5 3.5 3.5 2.5 3.5 3.5 0.4 250 0.3 Absorbance max(nm)[108] at max (x103 M1 cm1)[108]

In addition, there are two additional amino acids that are incorporated in response to stop codons (translational readthrough)