Amino acid

From Wikipedia, the free encyclopedia

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. In biochemistry, this term refers to alpha-amino acids with the general formula H₂NCHRCOOH, where R is an organic substituent.^[1] In the alpha amino acids, the amino and carboxylate groups are attached to the same carbon, which is called the α–carbon. The various alpha amino acids differ in which side chain (R group) is attached to their alpha carbon. They can vary in size from just a hydrogen atom in glycine through a methyl group in alanine to a large heterocyclic group in tryptophan.

Beyond the amino acids that are found in all forms of life, many non-natural amino acids have vital roles in technology and industry. For example, the chelating agents EDTA and nitrilotriacetic acid are alpha amino acids that are important in the chemical industry.

Contents 1 Overview 1.1 Functions in proteins 1.2 Non-protein functions 2 General structure 2.1 Isomerism 3 Reactions 3.1 Peptide bond formation 3.2 Zwitterions 4 Hydrophilic and hydrophobic amino acids 5 Table of standard amino acid abbreviations and side chain properties 6 Nonstandard amino acids 7 Uses in technology 8 Nutritional importance 9 See also 10 References and notes 11 Further reading 12 External links

[edit] Overview

Alpha-amino acids are the building blocks of proteins. Amino acids combine in a condensation reaction that releases water and the new "amino acid residue" that is held together by a peptide bond. Proteins are defined by their unique sequence of amino acid residues; this sequence is the primary structure of the protein. Just as the letters of the alphabet can be combined to form an almost endless variety of words, amino acids can be linked in varying sequences to form a vast variety of proteins.

Twenty standard amino acids are used by cells in protein biosynthesis, and these are specified by the general genetic code. These 20 amino acids are biosynthesized from other molecules, but organisms differ in which ones they can synthesize and which ones must be provided in their diet. The ones that cannot be synthesized by an organism are called essential amino acids.

[edit] Functions in proteins

See also: Primary structure and Posttranslational modification

Amino acids are the basic structural building units of proteins. They form short polymer chains called peptides or longer chains called either polypeptides or proteins. The process of such formation from an mRNA template is known as translation, which is part of protein biosynthesis. Twenty amino acids are encoded by the standard genetic code and are called proteinogenic or standard amino acids. Other amino acids contained in proteins are usually formed by post-translational modification, which is modification after translation in 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, and the hydroxylation of proline is critical for maintaining connective tissues and responding to oxygen starvation. 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.

[edit] Non-protein functions

The 20 standard amino acids are either used to synthesize proteins and other biomolecules or oxidized to urea and carbon dioxide as a source of energy.^[2] 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.^[3] Glucogenic amino acids can also be converted into glucose, through gluconeogenesis.^[4]

Hundreds of types of non-protein amino acids have been found in nature and they have multiple functions in living organisms. Microorganisms and plants can produce uncommon amino acids. In microbes, examples include 2-aminoisobutyric acid and lanthionine, which is a sulfide-bridged alanine dimer. Both these amino acids are both found in peptidic lantibiotics such as alamethicin.^[5] While in plants, 1-aminocyclopropane-1-carboxylic acid is a small disubstituted cyclic amino acid that is a key intermediate in the production of the plant hormone ethylene.^[6]

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

• Tryptophan is a precursor of the neurotransmitter serotonin.
• Glycine is a precursor of porphyrins such as heme.
• Arginine is a precursor of nitric oxide.
• Carnitine is used in lipid transport within the cell.
• Ornithine and S-adenosylmethionine are precursors of polyamines.
• Homocysteine is an intermediate in S-adenosylmethionine recycling.

Hydroxyproline, hydroxylysine, and sarcosine are also non-protein amino acids. The thyroid hormones are also alpha-amino acids.

Some amino acids have even been detected in meteorites, especially in a type known as carbonaceous chondrites.^[7] This observation has prompted the suggestion that life may have arrived on earth from an extraterrestrial source.

[edit] General structure

Further information: List of standard amino acids

In the structure shown at the right, R represents a side chain specific to each amino acid. The central carbon atom, called C_α, is a chiral central carbon atom (with the exception of glycine) to which the two termini and the R-group are attached. Amino acids are usually classified by the properties of the side chain into four groups. The side chain can make them behave like a weak acid, a weak base, a hydrophile if they are polar, and hydrophobe if they are nonpolar. The chemical structures of the 20 standard amino acids, along with their chemical properties, are catalogued in the list of standard amino acids.

The phrase "branched-chain amino acids" or BCAA is sometimes used to refer 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 α-amino group and, thus, is also the only proteinogenic amino acid containing a secondary amine at this position. Proline has sometimes been termed an imino acid, but this is not correct in the current nomenclature.^[8]

[edit] Isomerism

Most amino acids can exist in either of two optical isomers, called D and L. The L-amino acids represent the vast majority of amino acids found in proteins. D-amino acids are found in some proteins produced by exotic sea-dwelling organisms, such as cone snails.^[9] They are also abundant components of the peptidoglycan cell walls of bacteria.^[10]

The L and D conventions for amino acid configuration do not refer to the optical activity of the amino acid itself, but rather to the optical activity of the isomer of glyceraldehyde having the same stereochemistry as the amino acid. S-glyceraldehyde is levorotary, and R-glyceraldehyde is dexterorotary, and so S-amino acids are called L-amino acids even if they are not levorotary, and R-amino acids are likewise called D-amino acids even if they are not dexterorotary.

There are two exceptions to these general rules of amino acid isomerism. Firstly, glycine, where R = H, no isomerism is possible because the alpha-carbon bears two identical groups (hydrogen). Secondly, in cysteine, the L = S and D = R assignment is reversed to L = R and D = S. Cysteine is structured in the same way as the other amino acids but the sulfur atom alters the interpretation of the Cahn-Ingold-Prelog priority rule.

[edit] Reactions

As amino acids have both a primary amine group and a primary carboxyl group, these chemicals can undergo most of the reactions associated with these functional groups. These include nucleophilic addition, amide bond formation and imine formation for the amine group and esterification, amide bond formation and decarboxylation for the carboxylic acid group. The multiple side chains of amino acids can also undergo chemical reactions. The types of these reactions are determined by the groups on these side chains and are discussed in the articles dealing with each specific type of amino acid.

[edit] Peptide bond formation

For more details on this topic, see 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.^[11] 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.^[12] As a result of this mechanism, all proteins made by ribosomes are synthesized starting at their N-terminus and moving towards their C-terminus.

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.^[13] In the first step gamma-glutamylcysteine synthetase condenses cysteine and glutamic acid 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.^[14]

In chemistry, peptides are synthesized by a variety of reactions. One of the most used in solid-phase peptide synthesis, which 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.^[15]

[edit] Zwitterions

As amino acids have both the active groups of an amine and a carboxylic acid they can be considered both acid and base. At a certain pH known as the isoelectric point, the amine group has a positive charge (is protonated) and the acid group a negative charge (is deprotonated). The exact value is specific to each different amino acid. This ion is known as a zwitterion, which comes from the German word Zwitter meaning "hybrid". A zwitterion can be extracted from the solution as a white crystalline structure with a very high melting point, due to its dipolar nature. Near-neutral physiological pH allows most free amino acids to exist as zwitterions.

[edit] Hydrophilic and hydrophobic amino acids

Depending on the polarity of the side chain, amino acids vary in their hydrophilic or hydrophobic character. These properties are important in protein structure and protein-protein interactions. The importance of the physical properties of the side chains comes from the influence this has on the amino acid residues' interactions with other structures, both within a single protein and between proteins. The distribution of hydrophilic and hydrophobic amino acids determines the tertiary structure of the protein, and their physical location on the outside structure of the proteins influences their quaternary structure. For example, soluble proteins have surfaces rich with polar amino acids like serine and threonine, while integral membrane proteins tend to have outer ring of hydrophobic amino acids that anchors them into the lipid bilayer, and proteins anchored to the membrane have a hydrophobic end that locks into the membrane. Similarly, 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. Recently a new scale of hydrophobicity based on the free energy of hydrophobic association has been proposed.^[16]

Hydrophilic and hydrophobic interactions of the proteins do not have to rely only on the sidechains of amino acids themselves. By various posttranslational modifications other chains can be attached to the proteins, forming hydrophobic lipoproteins or hydrophilic glycoproteins.

[edit] Table of standard amino acid abbreviations and side chain properties

Main article: List of standard amino acids

Amino Acid	3-Letter	1-Letter	Side chain polarity	Side chain acidity or basicity of neutral species	Hydropathy index[17]
Alanine	Ala	A	nonpolar	neutral	1.8
Arginine	Arg	R	polar	basic (strongly)	-4.5
Asparagine	Asn	N	polar	neutral	-3.5
Aspartic acid	Asp	D	polar	acidic	-3.5
Cysteine	Cys	C	polar	neutral	2.5
Glutamic acid	Glu	E	polar	acidic	-3.5
Glutamine	Gln	Q	polar	neutral	-3.5
Glycine	Gly	G	nonpolar	neutral	-0.4
Histidine	His	H	polar	basic (weakly)	-3.2
Isoleucine	Ile	I	nonpolar	neutral	4.5
Leucine	Leu	L	nonpolar	neutral	3.8
Lysine	Lys	K	polar	basic	-3.9
Methionine	Met	M	nonpolar	neutral	1.9
Phenylalanine	Phe	F	nonpolar	neutral	2.8
Proline	Pro	P	nonpolar	neutral	-1.6
Serine	Ser	S	polar	neutral	-0.8
Threonine	Thr	T	polar	neutral	-0.7
Tryptophan	Trp	W	nonpolar	neutral	-0.9
Tyrosine	Tyr	Y	polar	neutral	-1.3
Valine	Val	V	nonpolar	neutral	4.2

In addition to the normal amino acid codes, placeholders were used historically in cases where chemical or crystallographic analysis of a peptide or protein could not completely establish the identity of a certain residue in a structure. The ones they could not resolve between are these pairs of amino-acids:

Ambiguous Amino Acids	3-Letter	1-Letter
Asparagine or aspartic acid	Asx	B
Glutamine or glutamic acid	Glx	Z
Leucine or Isoleucine	Xle	J
Unspecified or unknown amino acid	Xaa	X

Unk is sometimes used instead of Xaa, but is less standard.

[edit] Nonstandard amino acids

Aside from the twenty standard amino acids, there are a vast number of "non-standard" amino acids. Two of these can be specified by the genetic code, but are rather rare in proteins. Selenocysteine is incorporated into some proteins at a UGA codon, which is normally a stop codon.^[18] Pyrrolysine is used by some methanogenic archaea in enzymes that they use to produce methane. It is coded for with the codon UAG.^[19]

Examples of nonstandard amino acids that are not found in proteins 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.^[20]

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-adenosyl methionine,^[21] while dopamine is synthesized from l-DOPA, and hydroxyproline is made by a posttranslational modification of proline.^[22]

[edit] Uses in technology

Amino acid derivative	Use in industry
Aspartame (aspartyl-phenylalanine-1-methyl ester)	Low-calorie artificial sweetener
5-HTP (5-hydroxytryptophan)	Treatment for depression and the neurological problems of phenylketonuria.
L-DOPA (L-dihydroxyphenylalanine)	Treatment for Parkinsonism.
Monosodium glutamate	Food additive that enhances flavor. Confers the taste umami.

[edit] Nutritional importance

Further information: Protein in nutrition

Of the 20 standard proteinogenic amino acids, 8 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.^[23] However, the situation is a little more complicated since cysteine, tyrosine, histidine and arginine are semiessential amino acids in children, because the metabolic pathways that synthesize these amino acids are not fully developed.^[24] 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	Nonessential
Isoleucine	Alanine
Leucine	Asparagine
Lysine	Aspartate
Methionine	Cysteine*
Phenylalanine	Glutamate
Threonine	Glutamine*
Tryptophan	Glycine*
Valine	Proline*
Arginine*	Serine*
Histidine*	Tyrosine*

(*) Essential only in certain cases.^[25][26]

Several common mnemonics have evolved for remembering the ten amino acids often described as essential. PVT TIM HALL ("Private Tim Hall") uses the first letter of each of these amino acids.^[27] Another mnemonic that frequently occurs in student practice materials beneath "AH TV TILL Past Midnight", is "These ten valuable amino acids have long preserved life in man".^[28]

[edit] See also

• Biochemistry
• Beta amino acid
• Strecker amino acid synthesis
• Glucogenic amino acid
• Homochirality
• Murchison meteorite, an extraterrestrial source of amino acids.
• Table of codons, 3-nucleotide sequences that encode each amino acid
• List of standard amino acids (including chemical structures)
• Amino acid dating

[edit] References and notes

[edit] Further reading

• Doolittle, R.F. (1989) Redundancies in protein sequences. In Predictions of Protein Structure and the Principles of Protein Conformation (Fasman, G.D. ed) Plenum Press, New York, pp. 599-623
• David L. Nelson and Michael M. Cox, Lehninger Principles of Biochemistry, 3rd edition, 2000, Worth Publishers, ISBN 1-57259-153-6

[edit] External links

• Amino acids overview at Peptide Guide
• Nomenclature and Symbolism for Amino Acids and Peptides International Union of Pure and Applied Chemistry and The International Union of Biochemistry and Molecular Biology. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN)
• The PDF List of Standard Amino Acids
• Molecular Expressions: The Amino Acid Collection - Has detailed information and microscopy photographs of each amino acid.
• 22nd amino acid - Press release from Ohio State describing the discovery of pyrrolysine as a 22nd amino acid.
• Amino acid properties - Properties of the amino acids (a tool aimed mostly at molecular geneticists trying to understand the meaning of mutations)
• Synthesis of Amino Acids and Derivatives
• Right-handed amino acids were left behind
• Amino acid solutions pH, titration curves and distribution diagrams - freeware
• Protein isoelectric point according amino acids charge
• Learn the 20 proteinogenic amino acids online

v • d • e The 20 Common Amino Acids ("dp" = data page) Branched-chain amino acids Isoleucine (dp) | Leucine (dp) | Valine (dp) Other Alanine (dp) | Arginine (dp) | Asparagine (dp) | Aspartic acid (dp) | Cysteine (dp) | Glutamic acid (dp) | Glutamine (dp) | Glycine (dp) | Histidine (dp) | Lysine (dp) | Methionine (dp) | Phenylalanine (dp) | Proline (dp) | Serine (dp) | Threonine (dp) | Tryptophan (dp) | Tyrosine (dp) Major families of biochemicals Peptides | Amino acids | Nucleic acids | Carbohydrates | Nucleotide sugars | Lipids | Terpenes | Carotenoids | Tetrapyrroles | Enzyme cofactors | Steroids | Flavonoids | Alkaloids | Polyketides | Glycosides

v • d • e Protein primary structure and posttranslational modifications General Protein biosynthesis | Peptide bond | Proteolysis | Racemization | N-O acyl shift N terminus Acetylation | Formylation | Pyroglutamate | Methylation | Glycation | Myristoylation (Gly) | carbamylation C terminus Amidation | Glycosyl phosphatidylinositol (GPI) | O-methylation | Glypiation | Ubiquitination | Sumoylation Lysine Methylation | Acetylation | Acylation | Hydroxylation | Ubiquitination | SUMOylation | Desmosine | ADP-ribosylation | Deamination and Oxidation to aldehyde Cysteine Disulfide bond | Prenylation | Palmitoylation Serine/Threonine Phosphorylation | Glycosylation | Methylidene-imidazolone (MIO) formation Tyrosine Phosphorylation | Sulfation | Porphyrin ring linkage | Flavin linkage | p-Hydroxybenzylidene-imidazolone formation | Lysine tyrosyl quinone (LTQ) formation | Topaquinone (TPQ) formation Asparagine Deamidation | Glycosylation Aspartate Succinimide formation Glutamine Transglutamination Glutamate Carboxylation | Methylation | Polyglutamylation | Polyglycylation Arginine Citrullination | Methylation Proline Hydroxylation ←Amino acids Secondary structure→

v • d • e Metabolism: amino acid metabolism - synthesis and catabolism enzymes (essential in CAPS) K→acetyl-CoA LYSINE→ Saccharopine dehydrogenase - Glutaryl-CoA dehydrogenase LEUCINE→ Branched chain aminotransferase - Branched-chain alpha-keto acid dehydrogenase complex - Isovaleryl coenzyme A dehydrogenase - Methylcrotonyl-CoA carboxylase - Methylglutaconyl-CoA hydratase - 3-hydroxy-3-methylglutaryl-CoA lyase TRYPTOPHAN→ Indoleamine 2,3-dioxygenase/Tryptophan 2,3-dioxygenase - Arylformamidase - Kynureninase - 3-hydroxyanthranilate oxidase - Aminocarboxymuconate-semialdehyde decarboxylase - Aminomuconate-semialdehyde dehydrogenase PHENYLALANINE→tyrosine→ (see below) G→pyruvate glycine→serine→ Serine hydroxymethyltransferase - Serine dehydratase alanine→ Alanine transaminase cysteine→ D-cysteine desulfhydrase threonine→ L-threonine dehydrogenase G→glutamate HISTIDINE→ Histidine ammonia-lyase - Urocanate hydratase - Formiminotransferase cyclodeaminase proline→ Proline oxidase - Pyrroline-5-carboxylate reductase - 1-Pyrroline-5-carboxylate dehydrogenase/ALDH4A1 - PYCR1 arginine→ Ornithine aminotransferase - Ornithine decarboxylase - Agmatinase →alpha-ketoglutarate→TCA Glutamate dehydrogenase G→propionyl-CoA VALINE→ Branched chain aminotransferase - Branched-chain alpha-keto acid dehydrogenase complex - Enoyl-CoA hydratase - 3-hydroxyisobutyryl-CoA hydrolase - 3-hydroxyisobutyrate dehydrogenase - Methylmalonate semialdehyde dehydrogenase ISOLEUCINE→ Branched chain aminotransferase - Branched-chain alpha-keto acid dehydrogenase complex - 3-hydroxy-2-methylbutyryl-CoA dehydrogenase METHIONINE→ Methionine adenosyltransferase - Adenosylhomocysteinase - Cystathionine beta synthase - Cystathionine gamma-lyase (methionine synthesis: MTR/Homocysteine methyltransferase) THREONINE→ Threonine aldolase →succinyl-CoA→TCA Propionyl-CoA carboxylase - Methylmalonyl CoA epimerase - Methylmalonyl-CoA mutase G→fumarate PHENYLALANINE→tyrosine→ Phenylalanine hydroxylase - Tyrosine aminotransferase - 4-Hydroxyphenylpyruvate dioxygenase - Homogentisate 1,2-dioxygenase - Fumarylacetoacetate hydrolase G→oxaloacetate asparagine→aspartate→ Asparaginase/Asparagine synthetase - Aspartate transaminase Other tyrosine→melanin Tyrosinase cysteine+glutamate→glutathione Gamma-glutamylcysteine synthetase - Glutathione synthetase - Gamma-glutamyl transpeptidase glycine→creatine Guanidinoacetate N-methyltransferase - Creatine kinase glutamate→glutamine Glutamine synthetase - Glutaminase proline+lysine→collagen Prolyl hydroxylase - Lysyl hydroxylase see also disorders, intermediates