Amino acid

In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. In biochemistry, this shorter and more general term is frequently used to refer to alpha amino acids: those amino acids in which the amino and carboxylate functionalities are attached to the same carbon, the so-called α–carbon.

An amino acid residue is what is left of an amino acid once a molecule of water has been lost (an H⁺ from the nitrogenous side and an OH^- from the carboxylic side) in the formation of a peptide bond.

Overview

Amino acids are the basic structural building units of proteins. They form short polymer chains called peptides or polypeptides which in turn form structures called proteins. The process of such formation is known as translation, which is part of protein synthesis.

File:Phe-stick.png

Phenylalanine is one of the standard amino acids.

Twenty amino acids are encoded by the standard genetic code and are called proteinogenic or standard amino acids. At least two others are also coded by DNA in a non-standard manner as follows:

• Selenocysteine is incorporated into some proteins at a UGA codon, which is normally a stop codon.
• Pyrrolysine is used by some methanogens in enzymes that they use to produce methane. It is coded for similarly to selenocysteine but with the codon UAG instead.

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 of the protein.

Proline is the only proteinogenic amino acid whose side group is cyclic and links to the a-amino group, forming a secondary amino group. Formerly, proline was misleadingly called an imino acid.

Over one hundred amino acids have been found in nature. Some of these have been detected in meteorites, especially in a type known as carbonaceous chondrites. Microorganisms and plants can produce uncommon amino acids, which can be found in peptidic antibiotics (e.g., nisin or alamethicin). Lanthionine is a sulfide-bridged alanine dimer which is found together with unsaturated amino acids in lantibiotics (antibiotic peptides of microbial origin). 1-Aminocyclopropane-1-carboxylic acid (ACC) is a small disubstituted cyclic amino acid and a key intermediate in the production of the plant hormone ethylene.

In addition to protein synthesis, amino acids have other biologically-important roles. Glycine and glutamate are neurotransmitters as well as standard amino acids in proteins. Many amino acids are used to synthesize other molecules, for example:

• tryptophan is a precursor of the neurotransmitter serotonin
• glycine is one of the reactants in the synthesis of porphyrins such as heme.

Numerous non-standard amino acids are also biologically-important: Gamma-aminobutyric acid is another neurotransmitter, carnitine is used in lipid transport within a cell, ornithine, citrulline, homocysteine, hydroxyproline, hydroxylysine, and sarcosine.

Some of the 20 standard amino acids are called essential amino acids because they cannot be synthesized by the body from other compounds through chemical reactions, but instead must be taken in with food. In humans, the essential amino acids are lysine, leucine, isoleucine, methionine, phenylalanine, threonine, tryptophan, valine. Histidine and arginine are generally considered essential only in children, because of their inability to synthesise them given their undeveloped metabolisms.

The phrase "branched-chain amino acids" is sometimes used to refer to the aliphatic amino acids: leucine, isoleucine and valine.

General structure

The general structure of proteinogenic alpha amino acids is:

     R
     |
 H2N-C-COOH
     |
     H

Where R represents a side chain specific to each amino acid. 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.

Isomerism

Most amino acids occur in two possible optical isomers, called D and L. Using the newer Cahn Ingold Prelog priority rules for designating the configuration of optical isomers, the L isomer is assigned the letter S and the D isomer is assigned the letter R. 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. They are also abundant components of the proteoglycan cell walls of bacteria.

The L and D conventions for amino acid do not refer to their own optical activity, but rather to the optical activity of glyceraldehyde as an analogue of the amino acids. S-glyceraldehyde is levorotary, and R-glyceraldehyde is dexterorotary, and so S- amino acids are called "L-" even if they are not levorotary, and R- amino acids are likewise called "D-" even if they are not dexterorotary.

Exceptions

Two exceptions exist:

• In glycine, where R = H, and there is no isomerism, because two groups on the central carbon atom are identical

• In cysteine, the L-S and D-R assignment is reversed to L-R and D-S. Cysteine is structured similarly (with respect to glyceraldehyde) to the other amino acids but the sulfur atom alters the interpretation of the Cahn Ingold Prelog rules.

Reactions

Proteins are created by polymerization of amino acids by peptide bonds in a process called translation. This condensation reaction yields the newly formed peptide bond and a molecule of water.

Peptide bond formation

Peptide bond formation
1. Amino acid; 2, zwitterion structure; 3, two amino acids forming a peptide bond. (See also bond.)

List of standard amino acids

Structures

Structures and symbols of the 20 amino acids which are directly encoded for protein synthesis by the standard genetic code.

• 
  Alanine (Ala / A)
• 
  Arginine (Arg / R)
• 
  Asparagine (Asn / N)
• 
  Aspartic acid (Asp / D)
• 
  Cysteine (Cys / C)
• 
  Glutamic Acid (Glu / E)
• 
  Glutamine (Gln / Q)
• 
  Glycine (Gly / G)
• 
  Histidine (His / H)
• 
  Isoleucine (Ile / I)
• 
  Leucine (Leu / L)
• 
  Lysine (Lys / K)
• 
  Methionine (Met / M)
• 
  Phenylalanine (Phe / F)
• 
  Proline (Pro / P)
• 
  Serine (Ser / S)
• 
  Threonine (Thr / T)
• Tryptophan (Trp / W)
  Tryptophan (Trp / W)
• 
  Tyrosine (Tyr / Y)
• 
  Valine (Val / V)

Chemical properties

Following is a table listing the one letter symbols, the three-letter symbols, and the chemical properties of the side chains of the standard amino acids. The mass listed is the weighted average of all common isotopes, and includes the mass of H₂O. The one-letter symbol for an undetermined amino acid is X. The three-letter symbol Asx or one-letter symbol B means the amino acid is either asparagine or aspartic acid, whereas Glx or Z means either glutamic acid or glutamine. The three-letter symbol Sec or one-letter symbol U refers to selenocysteine. The letters J and O are not used.

Abbrev.		Full Name	Side chain type	Mass	pI	pK1 (α-COOH)	pK2 (α-+NH3)	pKr (R)	Remarks
A	Ala	Alanine	hydrophobic	89.09	6.01	2.35	9.87		Very abundant, very versatile. More stiff than glycine, but small enough to pose only small steric limits for the protein conformation. It behaves fairly neutrally, can be located in both hydrophilic regions on the protein outside and the hydrophobic areas inside.
C	Cys	Cysteine	hydrophobic (Nagano, 1999)	121.16	5.05	1.92	10.70	8.18	The sulfur atom binds readily to heavy metal ions. Under oxidizing conditions, two cysteines can join together by a disulfide bond to form the amino acid cystine. When cystines are part of a protein, insulin for example, this enforces tertiary structure and makes the protein more resistant to unfolding and denaturation; disulphide bridges are therefore common in proteins that have to function in harsh environments, digestive enzymes (e.g., pepsin and chymotrypsin), structural proteins (e.g., keratin), and proteins too small to hold their shape on their own (eg. insulin).
D	Asp	Aspartic acid	acidic	133.10	2.85	1.99	9.90	3.90	Behaves similarly to glutamic acid. Carries a hydrophilic acidic group with strong negative charge. Usually is located on the outer surface of the protein, making it water-soluble. Binds to positively-charged molecules and ions, often used in enzymes to fix the metal ion. When located inside of the protein, aspartate and glutamate are usually paired with arginine and lysine.
E	Glu	Glutamic acid	acidic	147.13	3.15	2.10	9.47	4.07	Behaves similar to aspartic acid. Has longer, slightly more flexible side chain.
F	Phe	Phenylalanine	hydrophobic	165.19	5.49	2.20	9.31		Essential for humans. Phenylalanine, tyrosine, and tryptophan contain large rigid aromatic group on the side chain. These are the biggest amino acids. Like isoleucine, leucine and valine, these are hydrophobic and tend to orient towards the interior of the folded protein molecule.
G	Gly	Glycine	hydrophobic	75.07	6.06	2.35	9.78		Because of the two hydrogen atoms at the α carbon, glycine is not optically active. It is the tiniest amino acid, rotates easily, adds flexibility to the protein chain. It is able to fit into the tightest spaces, e.g., the triple helix of collagen. As too much flexibility is usually not desired, as a structural component it is less common than alanine.
H	His	Histidine	basic	155.16	7.60	1.80	9.33	6.04	In even slightly acidic conditions protonation of the nitrogen occurs, changing the properties of histidine and the polypeptide as a whole. It is used by many proteins as a regulatory mechanism, changing the conformation and behavior of the polypeptide in acidic regions such as the late endosome or lysosome, enforcing conformation change in enzymes. However only a few histidines are needed for this, so it is comparatively scarce.
I	Ile	Isoleucine	hydrophobic	131.17	6.05	2.32	9.76		Essential for humans. Isoleucine, leucine and valine have large aliphatic hydrophobic side chains. Their molecules are rigid, and their mutual hydrophobic interactions are important for the correct folding of proteins, as these chains tend to be located inside of the protein molecule.
K	Lys	Lysine	basic	146.19	9.60	2.16	9.06	10.54	Essential for humans. Behaves similarly to arginine. Contains a long flexible side-chain with a positively-charged end. The flexibility of the chain makes lysine and arginine suitable for binding to molecules with many negative charges on their surfaces. E.g., DNA-binding proteins have their active regions rich with arginine and lysine. The strong charge makes these two amino acids prone to be located on the outer hydrophilic surfaces of the proteins; when they are found inside, they are usually paired with a corresponding negatively-charged amino acid, e.g., aspartate or glutamate.
L	Leu	Leucine	hydrophobic	131.17	6.01	2.33	9.74		Essential for humans. Behaves similar to isoleucine and valine. See isoleucine.
M	Met	Methionine	hydrophobic	149.21	5.74	2.13	9.28		Essential for humans. Always the first amino acid to be incorporated into a protein; sometimes removed after translation. Like cysteine, contains sulfur, but with a methyl group instead of hydrogen. This methyl group can be activated, and is used in many reactions where a new carbon atom is being added to another molecule.
N	Asn	Asparagine	hydrophilic	132.12	5.41	2.14	8.72		Neutralized version of aspartic acid.
P	Pro	Proline	hydrophobic	115.13	6.30	1.95	10.64		Contains an unusual ring to the N-end amine group, which forces the CO-NH amide sequence into a fixed conformation. Can disrupt protein folding structures like α helix or β sheet, forcing the desired kink in the protein chain. Common in collagen, where it undergoes a posttranslational modification to hydroxyproline. Uncommon elsewhere.
Q	Gln	Glutamine	hydrophilic	146.15	5.65	2.17	9.13		Neutralized version of glutamic acid. Used in proteins and as a storage for ammonia.
R	Arg	Arginine	basic	174.20	10.76	1.82	8.99	12.48	Functionally similar to lysine.
S	Ser	Serine	hydrophilic	105.09	5.68	2.19	9.21		Serine and threonine have a short group ended with a hydroxyl group. Its hydrogen is easy to remove, so serine and threonine often act as hydrogen donors in enzymes. Both are very hydrophylic, therefore the outer regions of soluble proteins tend to be rich with them.
T	Thr	Threonine	hydrophilic	119.12	5.60	2.09	9.10		Essential for humans. Behaves similarly to serine.
V	Val	Valine	hydrophobic	117.15	6.00	2.39	9.74		Essential for humans. Behaves similarly to isoleucine and leucine. See isoleucine.
W	Trp	Tryptophan	hydrophobic	204.23	5.89	2.46	9.41		Essential for humans. Behaves similarly to phenylalanine and tyrosine (see phenylalanine). Precursor of serotonin.
Y	Tyr	Tyrosine	hydrophobic	181.19	5.64	2.20	9.21	10.46	Behaves similarly to phenylalanine and tryptophan (see phenylalanine). Precursor of melanin, epinephrine, and thyroid hormones.

Amino acid	Abbrev.	Side chain	Hydro- phobic	Polar	Charged	Small	Tiny	Aromatic or Aliphatic	van der Waals volume	Codon	Occurrence in proteins (%)
Alanine	Ala, A	-CH3	X	-	-	X	X	-	67	GCU, GCC, GCA, GCG	7.8
Cysteine	Cys, C	-CH2SH	X	-	-	X	-	-	86	UGU, UGC	1.9
Aspartate	Asp, D	-CH2COOH	-	X	negative	X	-	-	91	GAU, GAC	5.3
Glutamate	Glu, E	-CH2CH2COOH	-	X	negative	-	-	-	109	GAA, GAG	6.3
Phenylalanine	Phe, F	-CH2C6H5	X	-	-	-	-	Aromatic	135	UUU, UUC	3.9
Glycine	Gly, G	-H	X	-	-	X	X	-	48	GGU, GGC, GGA, GGG	7.2
Histidine	His, H	-CH2-C3H3N2	-	X	positive	-	-	Aromatic	118	CAU, CAC	2.3
Isoleucine	Ile, I	-CH(CH3)CH2CH3	X	-	-	-	-	Aliphatic	124	AUU, AUC, AUA	5.3
Lysine	Lys, K	-(CH2)4NH2	-	X	positive	-	-	-	135	AAA, AAG	5.9
Leucine	Leu, L	-CH2CH(CH3)2	X	-	-	-	-	Aliphatic	124	UUA, UUG, CUU, CUC, CUA, CUG	9.1
Methionine	Met, M	-CH2CH2SCH3	X	-	-	-	-	-	124	AUG	2.3
Asparagine	Asn, N	-CH2CONH2	-	X	-	X	-	-	96	AAU, AAC	4.3
Proline	Pro, P	-CH2CH2CH2-	X	-	-	X	-	-	90	CCU, CCC, CCA, CCG	5.2
Glutamine	Gln, Q	-CH2CH2CONH2	-	X	-	-	-	-	114	CAA, CAG	4.2
Arginine	Arg, R	-(CH2)3NH-C(NH)NH2	-	X	positive	-	-	-	148	CGU, CGC, CGA, CGG, AGA, AGG	5.1
Serine	Ser, S	-CH2OH	-	X	-	X	X	-	73	UCU, UCC, UCA, UCG, AGU,AGC	6.8
Threonine	Thr, T	-CH(OH)CH3	X	X	-	X	-	-	93	ACU, ACC, ACA, ACG	5.9
Valine	Val, V	-CH(CH3)2	X	-	-	X	-	Aliphatic	105	GUU, GUC, GUA, GUG	6.6
Tryptophan	Trp, W	-CH2C8H6N	X	-	-	-	-	Aromatic	163	UGG	1.4
Tyrosine	Tyr, Y	-CH2-C6H4OH	X	X	-	-	-	Aromatic	141	UAU, UAC	3.2

Hydrophilic and hydrophobic amino acids

The Amino Acid Properties

The Amino Acid Properties

Depending on how polar the side chain, aminoacids can be hydrophilic or hydrophobic to various degree. This influences their interaction with other structures, both within the protein itself and within other proteins. The distribution of hydrophilic and hydrophobic aminoacids 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 aminoacids like serine and threonine, while integral membrane proteins tend to have outer ring of hydrophobic aminoacids that anchors them to 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 positive-charged molecules have surfaces rich with negatively charged aminoacids like glutamate and aspartate, while proteins binding to negative-charged molecules have surfaces rich with positively charged chains like lysine and arginine.

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

Nonstandard amino acids

Aside from the twenty standard amino acids and the two special amino acids, selenocysteine and pyrrolysine, already mentioned above, there are a vast number of "nonstandard amino acids" which are not incorporated into protein. Examples of nonstandard amino acids include the sulfur-containing taurine and the neurotransmitters GABA and dopamine. Other examples are lanthionine, 2-Aminoisobutyric acid, and dehydroalanine. Nonstandard amino acids often occur in the metabolic pathways for standard amino acids - for example ornithine and citrulline occur in the urea cycle, part of amino acid breakdown.

Nonstandard amino acids are usually formed through modifications to standard amino acids. For example, taurine can be formed by the decarboxylation of cysteine, while dopamine is synthesized from tyrosine and hydroxyproline is made by a posttranslational modification of proline (common in collagen).

Uses of substances derived from amino acids

• Aspartame (aspartyl-phenylalanine-1-methyl ester) is an artificial sweetener.
• 5-HTP (5-hydroxytryptophan) has been used to treat neurological problems associated with PKU (phenylketonuria), as well as depression (as an alternative to L-Tryptophan).
• L-DOPA (L-dihydroxyphenylalanine) is a drug used to treat Parkinsonism.
• Monosodium glutamate is a food additive to enhance flavor.

See also

• Essential amino acids
• Strecker amino acid synthesis

References

• 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 1572591536
• On the hydrophobic nature of cysteine.

External links

• Molecular Expressions: The Amino Acid Collection - Has detailed information and microscopy photographs of each amino acid.
• 22nd amino acid - Press release from Ohio State claiming discovery of a 22nd amino acid.
• Amino acid properties - Properties of the amino acids (a tool aimed mostly and molecular geneticists trying to understand the meaning of mutations)