Proteinogenic amino acid
Proteinogenic amino acids are amino acids that are precursors to proteins, and are incorporated into proteins cotranslationally - that is, during translation. There are 23 proteinogenic amino acids, but only 20 are encoded by the nuclear genes of eukaryotes. Of the 23, selenocysteine and pyrrolysine are incorporated into proteins by distinct post-translational biosynthetic mechanisms, and N-formylmethionine is often the initial amino acid of proteins in bacteria, mitochondria, and chloroplasts, but is often removed post-translationally. The other 20 are directly encoded by the genetic code. Humans can synthesize 11 of these 20 from each other or from other molecules of intermediary metabolism. The other 9 must be consumed (usually as their protein derivatives) in the diet and so are thus called essential amino acids. The essential amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.
The word proteinogenic means "protein building". Proteinogenic amino acids can be condensed into a polypeptide (the subunit of a protein) through a process called translation (the second stage of protein biosynthesis, part of the overall process of gene expression).
In contrast, non-proteinogenic amino acids are either not incorporated in proteins (like GABA, L-DOPA, or triiodothyronine), or are not produced directly and in isolation by standard cellular machinery (like hydroxyproline and selenomethionine). The latter often results from posttranslational modification of proteins.
The proteinogenic amino acids have been found to be related to the set of amino acids that can be recognized by ribozyme auto-aminoacylation systems. Thus, non-proteinogenic amino acids would have been excluded by the contingent evolutionary success of nucleotide-based life forms. Other reasons have been offered to explain why certain specific non-proteinogenic amino acids are not generally incorporated into proteins: for example, ornithine and homoserine cyclize against the peptide backbone and fragment the protein with relatively short half-lives, while others are toxic because they can be mistakenly incorporated into proteins, such as the arginine analog canavanine.
Non-proteinogenic amino acids are incorporated in nonribosomal peptides, which are not produced by the ribosome during translation.
The following illustrates the structures and abbreviations of the 21 amino acids that are directly encoded for protein synthesis by the genetic code of eukaryotes. The structures given below are standard chemical structures, not the typical zwitterion forms that exist in aqueous solutions.
(Ala / A)
(Arg / R)
(Asn / N)
(Asp / D)
(Cys / C)
(Glu / E)
(Gln / Q)
(Gly / G)
(His / H)
(Ile / I)
(Leu / L)
(Lys / K)
(Met / M)
(Phe / F)
(Pro / P)
(Ser / S)
(Thr / T)
(Trp / W)
(Tyr / Y)
(Val / V)
Sometimes the specific identity of an amino acid cannot be determined unambiguously. Certain protein sequencing techniques do not distinguish among certain pairs. Thus, the following codes are used:
- Asx (B) is "asparagine or aspartic acid"
- Glx (Z) is "glutamic acid or glutamine"
- Xle (J) is "leucine or isoleucine"
In addition, the symbol X is used to indicate an amino acid that is completely unidentified.
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 masses listed are based on weighted averages of the elemental isotopes at their natural abundances. Note that forming a peptide bond results in elimination of a molecule of water, so the mass of an amino acid unit within a protein chain is reduced by 18.01524 Da.
General chemical properties
|Amino Acid||Short||Abbrev.||Avg. Mass (Da)||pI||pK1
Side chain properties
|Amino Acid||Short||Abbrev.||Side chain||Hydro-
|van der Waals
Note: The pKa values of amino acids are typically slightly different when the amino acid is inside a protein. Protein pKa calculations are sometimes used to calculate the change in the pKa value of an amino acid in this situation.
Gene expression and biochemistry
in human proteins
|Essential‡ in humans|
|Alanine||A||Ala||GCU, GCC, GCA, GCG||7.8||No|
|Aspartic acid||D||Asp||GAU, GAC||5.3||No|
|Glutamic acid||E||Glu||GAA, GAG||6.3||Conditionally|
|Glycine||G||Gly||GGU, GGC, GGA, GGG||7.2||Conditionally|
|Isoleucine||I||Ile||AUU, AUC, AUA||5.3||Yes|
|Leucine||L||Leu||UUA, UUG, CUU, CUC, CUA, CUG||9.1||Yes|
|Proline||P||Pro||CCU, CCC, CCA, CCG||5.2||No|
|Arginine||R||Arg||CGU, CGC, CGA, CGG, AGA, AGG||5.1||Conditionally|
|Serine||S||Ser||UCU, UCC, UCA, UCG, AGU, AGC||6.8||No|
|Threonine||T||Thr||ACU, ACC, ACA, ACG||5.9||Yes|
|Valine||V||Val||GUU, GUC, GUA, GUG||6.6||Yes|
|Stop codon†||-||Term||UAA, UAG, UGA††||-||-|
* UAG is normally the amber stop codon, but encodes pyrrolysine if a PYLIS element is present.
** UGA is normally the opal (or umber) stop codon, but encodes selenocysteine if a SECIS element is present.
† The stop codon is not an amino acid, but is included for completeness.
†† UAG and UGA do not always act as stop codons (see above).
‡ An essential amino acid cannot be synthesized in humans and must, therefore, be supplied in the diet. Conditionally essential amino acids are not normally required in the diet, but must be supplied exogenously to specific populations that do not synthesize it in adequate amounts.
|Amino Acid||Short||Abbrev.||Formula||Mon. Mass§ (Da)||Avg. Mass (Da)|
Stoichiometry and metabolic cost in cell
Following table lists the abundance of amino acids in E.coli cell and the metabolic cost (ATP) for synthesis the amino acids. Negative numbers indicate the metabolic processes are energy favorable and do not cost net ATP of the cell. Note that the abundance of amino acids include amino acids in free-form and in polymerization form (proteins).
(# of molecules (×108)
per E. coli cell)
|ATP cost in synthesis
|ATP cost in synthesis
|Alanine||A||Ala||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, and can be located in both hydrophilic regions on the protein outside and the hydrophobic areas inside.|
|Asparagine or aspartic acid||B||Asx||A placeholder when either amino acid may occupy a position.|
|Cysteine||C||Cys||The sulfur atom bonds readily to heavy metal ions. Under oxidizing conditions, two cysteines can join together in a disulfide bond to form the amino acid cystine. When cystines are part of a protein, insulin for example, the tertiary structure is stabilized, which makes the protein more resistant to denaturation; therefore, disulfide bonds are common in proteins that have to function in harsh environments including digestive enzymes (e.g., pepsin and chymotrypsin) and structural proteins (e.g., keratin). Disulfides are also found in peptides too small to hold a stable shape on their own (e.g. insulin).|
|Aspartic acid||D||Asp||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.|
|Glutamic acid||E||Glu||Behaves similarly to aspartic acid. Has longer, slightly more flexible side chain.|
|Phenylalanine||F||Phe||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. Phenylalanine can be converted into Tyrosine.|
|Glycine||G||Gly||Because of the two hydrogen atoms at the α carbon, glycine is not optically active. It is the smallest 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.|
|Histidine||H||His||Essential for humans. 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.|
|Isoleucine||I||Ile||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.|
|Leucine or isoleucine||J||Xle||A placeholder when either amino acid may occupy a position|
|Lysine||K||Lys||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.|
|Leucine||L||Leu||Essential for humans. Behaves similar to isoleucine and valine. See isoleucine.|
|Methionine||M||Met||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.|
|Asparagine||N||Asn||Similar to aspartic acid. Asn contains an amide group where Asp has a carboxyl.|
|Pyrrolysine||O||Pyl||Similar to lysine, with a pyrroline ring attached.|
|Proline||P||Pro||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 often undergoes a posttranslational modification to hydroxyproline.|
|Glutamine||Q||Gln||Similar to glutamic acid. Gln contains an amide group where Glu has a carboxyl. Used in proteins and as a storage for ammonia. The most abundant Amino Acid in the body.|
|Arginine||R||Arg||Functionally similar to lysine.|
|Serine||S||Ser||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 hydrophilic, therefore the outer regions of soluble proteins tend to be rich with them.|
|Threonine||T||Thr||Essential for humans. Behaves similarly to serine.|
|Selenocysteine||U||Sec||Selenated form of cysteine, which replaces sulfur.|
|Valine||V||Val||Essential for humans. Behaves similarly to isoleucine and leucine. See isoleucine.|
|Tryptophan||W||Trp||Essential for humans. Behaves similarly to phenylalanine and tyrosine (see phenylalanine). Precursor of serotonin. Naturally fluorescent.|
|Unknown||X||Xaa||Placeholder when the amino acid is unknown or unimportant.|
|Tyrosine||Y||Tyr||Behaves similarly to phenylalanine (precursor to Tyrosine) and tryptophan (see phenylalanine). Precursor of melanin, epinephrine, and thyroid hormones. Naturally fluorescent, although fluorescence is usually quenched by energy transfer to tryptophans.|
|Glutamic acid or glutamine||Z||Glx||A placeholder when either amino acid may occupy a position.|
Life based on alternative proteinogenic sets
The proteinogenic used by known life on Earth appears to abitrarily selected by evolution, according to current knowledge, from many hundreds of possible alpha-type amino acids. Xenobiology studies hypothetical life forms that could be constructed using alternative sets using expanded genetic codes. Miller type experiences on artificial abiogenesis show that alpha-type amino acids predominate in water-based 'primordial soups' but beta-type amino acids dominate when there is less water. Both alpha and beta based sets could form the basis for alternative protein constructions and life forms.
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- "The amino acid masses". ExPASy. Retrieved 2009-01-06.
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- Chapter 20 (Amino Acid Degradation and Synthesis) in: Denise R., PhD. Ferrier. Lippincott's Illustrated Reviews: Biochemistry (Lippincott's Illustrated Reviews). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-2265-9.
- Nelson, David L.; Cox, Michael M. (2000). Lehninger Principles of Biochemistry (3rd ed.). Worth Publishers. ISBN 1-57259-153-6.
- Kyte, J.; Doolittle, R. F. (1982). "A simple method for displaying the hydropathic character of a protein". J. Mol. Biol. 157 (1): 105–132. doi:10.1016/0022-2836(82)90515-0. PMID 7108955.
- Meierhenrich, Uwe J. (2008). Amino acids and the asymmetry of life (1st ed.). Springer. ISBN 978-3-540-76885-2.