Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation from RNA. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino acids, 20 in the standard genetic code and an additional 2 (selenocysteine and pyrrolysine) that can be incorporated by special translation mechanisms.
In contrast, non-proteinogenic amino acids are amino acids that are either not incorporated into proteins (like GABA, L-DOPA, or triiodothyronine), misincorporated in place of a genetically encoded amino acid, or not produced directly and in isolation by standard cellular machinery (like hydroxyproline). The latter often results from post-translational modification of proteins. Some non-proteinogenic amino acids are incorporated into nonribosomal peptides which are synthesized by non-ribosomal peptide synthetases.
Both eukaryotes and prokaryotes can incorporate selenocysteine into their proteins via a nucleotide sequence known as a SECIS element, which directs the cell to translate a nearby UGA codon as selenocysteine (UGA is normally a stop codon). In some methanogenic prokaryotes, the UAG codon (normally a stop codon) can also be translated to pyrrolysine.
In eukaryotes, there are only 21 proteinogenic amino acids, the 20 of the standard genetic code, plus selenocysteine. Humans can synthesize 12 of these from each other or from other molecules of intermediary metabolism. The other nine must be consumed (usually as their protein derivatives), and so they are called essential amino acids. The essential amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine (i.e. H, I, L, K, M, F, T, W, V).
The proteinogenic amino acids have been found to be related to the set of amino acids that can be recognized by ribozyme autoaminoacylation 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.
The evolutionary selection of certain proteinogenic amino acids from the primordial soup has been suggested to be because of their better incorporation into a polypeptide chain as opposed to non-proteinogenic amino acids.
Structures 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.
IUPAC/IUBMB now also recommends standard abbreviations for the following two amino acids:
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 masses listed are based on weighted averages of the elemental isotopes at their natural abundances. Forming a peptide bond results in elimination of a molecule of water. Therefore, the protein's mass is equal to the mass of amino acids the protein is composed of minus 18.01524 Da per peptide bond.
General chemical properties Amino acid Short Avg. mass (Da) pK1(α-COO−) pK2(α-NH3+) Alanine A Ala 89.09404 6.01 2.35 9.87 Cysteine C Cys 121.15404 5.05 1.92 10.70 Aspartic acid D Asp 133.10384 2.85 1.99 9.90 Glutamic acid E Glu 147.13074 3.15 2.10 9.47 Phenylalanine F Phe 165.19184 5.49 2.20 9.31 Glycine G Gly 75.06714 6.06 2.35 9.78 Histidine H His 155.15634 7.60 1.80 9.33 Isoleucine I Ile 131.17464 6.05 2.32 9.76 Lysine K Lys 146.18934 9.60 2.16 9.06 Leucine L Leu 131.17464 6.01 2.33 9.74 Methionine M Met 149.20784 5.74 2.13 9.28 Asparagine N Asn 132.11904 5.41 2.14 8.72 Pyrrolysine O Pyl 255.31 Proline P Pro 115.13194 6.30 1.95 10.64 Glutamine Q Gln 146.14594 5.65 2.17 9.13 Arginine R Arg 174.20274 10.76 1.82 8.99 Serine S Ser 105.09344 5.68 2.19 9.21 Threonine T Thr 119.12034 5.60 2.09 9.10 Selenocysteine U Sec 168.053 5.47 1.91 10 Valine V Val 117.14784 6.00 2.39 9.74 Tryptophan W Trp 204.22844 5.89 2.46 9.41 Tyrosine Y Tyr 181.19124 5.64 2.20 9.21
Side-chain properties
Amino acid Short Side chain Hydro-phobic Polar pH Small Tiny Aromaticor Aliphatic van der Waalsvolume (Å3) Alanine A Ala -CH3 - - Aliphatic 67 Cysteine C Cys -CH2SH 8.55 acidic - 86 Aspartic acid D Asp -CH2C(O)OH 3.67 acidic - 91 Glutamic acid E Glu -CH2CH2C(O)OH 4.25 acidic - 109 Phenylalanine F Phe -CH2C6H5 - - Aromatic 135 Glycine G Gly -H - - - 48 Histidine H His -CH2-C3H3N2 6.54 weak basic Aromatic 118 Isoleucine I Ile -CH(CH3)CH2CH3 - - Aliphatic 124 Lysine K Lys -(CH2)4NH2 10.40 basic - 135 Leucine L Leu -CH2CH(CH3)2 - - Aliphatic 124 Methionine M Met -CH2CH2SCH3 - - Aliphatic 124 Asparagine N Asn -CH2C(O)NH2 - - - 96 Pyrrolysine O Pyl -(CH2)4NHCOC4H5NCH3 weak basic - Proline P Pro -CH2CH2CH2- - - - 90 Glutamine Q Gln -CH2CH2C(O)NH2 - - - 114 Arginine R Arg -(CH2)3NH-C(NH)NH2 12.3 strongly basic - 148 Serine S Ser -CH2OH - - - 73 Threonine T Thr -CH(OH)CH3 - - - 93 Selenocysteine U Sec -CH2SeH 5.43 acidic - Valine V Val -CH(CH3)2 - - Aliphatic 105 Tryptophan W Trp -CH2C8H6N - - Aromatic 163 Tyrosine Y Tyr -CH2-C6H4OH 9.84 weak acidic Aromatic 141
§: Only ionizable residues have a meaningful pKa. Values for Asp, Cys, Glu, His, Lys & Tyr were determined using the amino acid residue placed centrally in an alanine pentapeptide. The value for Arg is from Pace et al. (2009). The value for Sec is from Byun & Kang (2011).
Note: the pKa value of an amino-acid residue in a small peptide is typically slightly different when it is inside a protein. Protein pKa calculations are sometimes used to calculate the change in the pKa value of an amino-acid residue in this situation.
Gene expression and biochemistry Amino acid Short Codon(s) Occurrence Essential‡ in humans in Archaean proteins(%)& in Bacteria proteins(%)& in Eukaryote proteins(%)& in human proteins(%)& Alanine A Ala GCU, GCC, GCA, GCG8.210.067.63 7.01 Cysteine C Cys UGU, UGC0.980.941.76 2.3 Aspartic acid D Asp GAU, GAC6.215.595.4 4.73 Glutamic acid E Glu GAA, GAG7.696.156.42 7.09 Phenylalanine F Phe UUU, UUC 3.863.893.87 3.65 Glycine G Gly GGU, GGC, GGA, GGG 7.587.766.33 6.58 Histidine H His CAU, CAC1.772.062.44 2.63 Isoleucine I Ile AUU, AUC, AUA7.035.895.1 4.33 Lysine K Lys AAA, AAG5.274.685.64 5.72 Leucine L Leu UUA, UUG, CUU, CUC, CUA, CUG9.3110.099.29 9.97 Methionine M Met AUG2.352.382.25 2.13 Asparagine N Asn AAU, AAC3.683.584.28 3.58 Pyrrolysine O Pyl UAG*000 0 Proline P Pro CCU, CCC, CCA, CCG 4.264.615.41 6.31 Glutamine Q Gln CAA, CAG2.383.584.21 4.77 Arginine R Arg CGU, CGC, CGA, CGG, AGA, AGG5.515.885.71 5.64 Serine S Ser UCU, UCC, UCA, UCG, AGU, AGC6.175.858.34 8.33 Threonine T Thr ACU, ACC, ACA, ACG 5.445.525.56 5.36 Selenocysteine U Sec UGA**000 >0 Valine V Val GUU, GUC, GUA, GUG 7.87.276.2 5.96 Tryptophan W Trp UGG 1.031.271.24 1.22 Tyrosine Y Tyr UAU, UAC 3.352.942.87 2.66 Stop codon† - Term UAA, UAG, UGA†† * UAG is normally the amber stop codon, but in organisms containing the biological machinery encoded by the pylTSBCD cluster of genes the amino acid pyrrolysine will be incorporated. ** 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. & Occurrence of amino acids is based on 135 Archaea, 3775 Bacteria, 614 Eukaryota proteomes and human proteome (21 006 proteins) respectively.
Mass spectrometry In mass spectrometry of peptides and proteins, knowledge of the masses of the residues is useful. The mass of the peptide or protein is the sum of the residue masses plus the mass of water (Monoisotopic mass = 18.01056 Da; average mass = 18.0153 Da). The residue masses are calculated from the tabulated chemical formulas and atomic weights. In mass spectrometry, ions may also include one or more protons (Monoisotopic mass = 1.00728 Da; average mass* = 1.0074 Da). *Protons cannot have an average mass, this confusingly infers to Deuterons as a valid isotope, but they should be a different species (see Hydron (chemistry))
Amino acid Short Formula Mon. mass§ () () Alanine A Ala C3H5NO 71.03711 71.0779 Cysteine C Cys C3H5NOS 103.00919 103.1429 Aspartic acid D Asp C4H5NO3 115.02694 115.0874 Glutamic acid E Glu C5H7NO3 129.04259 129.1140 Phenylalanine F Phe C9H9NO 147.06841147.1739 Glycine G Gly C2H3NO 57.02146 57.0513 Histidine H His C6H7N3O 137.05891 137.1393 Isoleucine I Ile C6H11NO 113.08406 113.1576 Lysine K Lys C6H12N2O 128.09496 128.1723 Leucine L Leu C6H11NO 113.08406 113.1576 Methionine M Met C5H9NOS 131.04049 131.1961 Asparagine N Asn C4H6N2O2 114.04293 114.1026 Pyrrolysine O Pyl C12H19N3O2 237.14773 237.2982 Proline P Pro C5H7NO 97.05276 97.1152 Glutamine Q Gln C5H8N2O2 128.05858 128.1292 Arginine R Arg C6H12N4O 156.10111 156.1857 Serine S Ser C3H5NO2 87.03203 87.0773 Threonine T Thr C4H7NO2 101.04768 101.1039 Selenocysteine U Sec C3H5NOSe 150.95364 150.0489 Valine V Val C5H9NO 99.06841 99.1311 Tryptophan W Trp C11H10N2O 186.07931 186.2099 Tyrosine Y Tyr C9H9NO2 163.06333 163.1733 § Monoisotopic mass
Stoichiometry and metabolic cost in cell The table below lists the abundance of amino acids in E.coli cells and the metabolic cost (ATP) for synthesis of the amino acids. Negative numbers indicate the metabolic processes are energy favorable and do not cost net ATP of the cell. The abundance of amino acids includes amino acids in free form and in polymerization form (proteins).
Amino acid Short Abundance (# of molecules (×108)per E. coli cell) ATP cost in synthesis Aerobicconditions Anaerobicconditions Alanine A Ala 2.9 −1 1 Cysteine C Cys 0.52 11 15 Aspartic acid D Asp 1.4 0 2 Glutamic acid E Glu 1.5 −7 −1 Phenylalanine F Phe 1.1 −6 2 Glycine G Gly 3.5 −2 2 Histidine H His 0.54 1 7 Isoleucine I Ile 1.7 7 11 Lysine K Lys 2.0 5 9 Leucine L Leu 2.6 −9 1 Methionine M Met 0.88 21 23 Asparagine N Asn 1.4 3 5 Pyrrolysine O Pyl - - - Proline P Pro 1.3 −2 4 Glutamine Q Gln 1.5 −6 0 Arginine R Arg 1.7 5 13 Serine S Ser 1.2 −2 2 Threonine T Thr 1.5 6 8 Selenocysteine U Sec - - - Valine V Val 2.4 −2 2 Tryptophan W Trp 0.33 −7 7 Tyrosine Y Tyr 0.79 −8 2
Remarks