Proteinogenic amino acid

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Proteinogenic amino acids are a small fraction of all amino acids

Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. 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 that can be incorporated by special translation mechanisms.[1]

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.[2]

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).[3]

The proteinogenic amino acids have been found to be related to the set of amino acids that can be recognized by ribozyme autoaminoacylation systems.[4] 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.

Structures[edit]

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.

Table of amino acids
Grouped table of 21 amino acids' structures, nomenclature, and their side groups' pKa values

IUPAC/IUBMB now also recommends standard abbreviations for the following two amino acids:

Chemical properties[edit]

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, 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
(α-COOH)
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[edit]

Amino acid Short Abbrev. Side chain Hydro-
phobic
pKa§ Polar pH Small Tiny Aromatic
or Aliphatic
van der Waals
volume
3)
Alanine A Ala -CH3 Yes - No - Yes Yes Aliphatic 67
Cysteine C Cys -CH2SH Yes 8.55 No acidic Yes Yes - 86
Aspartic acid D Asp -CH2COOH No 3.67 Yes acidic Yes No - 91
Glutamic acid E Glu -CH2CH2COOH No 4.25 Yes acidic No No - 109
Phenylalanine F Phe -CH2C6H5 Yes - No - No No Aromatic 135
Glycine G Gly -H Yes - No - Yes Yes - 48
Histidine H His -CH2-C3H3N2 No 6.54 Yes weak basic No No Aromatic 118
Isoleucine I Ile -CH(CH3)CH2CH3 Yes - No - No No Aliphatic 124
Lysine K Lys -(CH2)4NH2 No 10.40 Yes basic No No - 135
Leucine L Leu -CH2CH(CH3)2 Yes - No - No No Aliphatic 124
Methionine M Met -CH2CH2SCH3 Yes - No - No No Aliphatic 124
Asparagine N Asn -CH2CONH2 No - Yes - Yes No - 96
Pyrrolysine O Pyl -(CH2)4NHCOC4H5NCH3 No N.D. Yes weak basic No No - ?
Proline P Pro -CH2CH2CH2- Yes - No - Yes No - 90
Glutamine Q Gln -CH2CH2CONH2 No - Yes - No No - 114
Arginine R Arg -(CH2)3NH-C(NH)NH2 No 12.3 Yes strongly basic No No - 148
Serine S Ser -CH2OH No - Yes - Yes Yes - 73
Threonine T Thr -CH(OH)CH3 No - Yes - Yes No - 93
Selenocysteine U Sec -CH2SeH No 5.43 No acidic Yes Yes - ?
Valine V Val -CH(CH3)2 Yes - No - Yes No Aliphatic 105
Tryptophan W Trp -CH2C8H6N Yes - No - No No Aromatic 163
Tyrosine Y Tyr -CH2-C6H4OH No 9.84 Yes weak acidic No No Aromatic 141

§: Values for Asp, Cys, Glu, His, Lys & Tyr were determined using the amino acid residue placed centrally in an alanine pentapeptide.[5] The value for Arg is from Pace et al. (2009).[6] The value for Sec is from Byun & Kang (2011).[7]

N.D.: The pKa value of Pyrrolysine has not been reported.

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[edit]

Amino acid Short Abbrev. Codon(s) Occurrence Essential in humans
in Archaean proteins
(%)&
in Bacteria proteins
(%)&
in Eukaryote proteins
(%)&
Occurrence
in human proteins
(%)&
Alanine A Ala GCU, GCC, GCA, GCG 8.2 10.06 7.63 7.01 No
Cysteine C Cys UGU, UGC 0.98 0.94 1.76 2.3 Conditionally
Aspartic acid D Asp GAU, GAC 6.21 5.59 5.4 4.73 No
Glutamic acid E Glu GAA, GAG 7.69 6.15 6.42 7.09 Conditionally
Phenylalanine F Phe UUU, UUC 3.86 3.89 3.87 3.65 Yes
Glycine G Gly GGU, GGC, GGA, GGG 7.58 7.76 6.33 6.58 Conditionally
Histidine H His CAU, CAC 1.77 2.06 2.44 2.63 Yes
Isoleucine I Ile AUU, AUC, AUA 7.03 5.89 5.1 4.33 Yes
Lysine K Lys AAA, AAG 5.27 4.68 5.64 5.72 Yes
Leucine L Leu UUA, UUG, CUU, CUC, CUA, CUG 9.31 10.09 9.29 9.97 Yes
Methionine M Met AUG 2.35 2.38 2.25 2.13 Yes
Asparagine N Asn AAU, AAC 3.68 3.58 4.28 3.58 No
Pyrrolysine O Pyl UAG* 0 0 0 0 No
Proline P Pro CCU, CCC, CCA, CCG 4.26 4.61 5.41 6.31 No
Glutamine Q Gln CAA, CAG 2.38 3.58 4.21 4.77 No
Arginine R Arg CGU, CGC, CGA, CGG, AGA, AGG 5.51 5.88 5.71 5.64 Conditionally
Serine S Ser UCU, UCC, UCA, UCG, AGU, AGC 6.17 5.85 8.34 8.33 No
Threonine T Thr ACU, ACC, ACA, ACG 5.44 5.52 5.56 5.36 Yes
Selenocysteine U Sec UGA** 0 0 0 >0 No
Valine V Val GUU, GUC, GUA, GUG 7.8 7.27 6.2 5.96 Yes
Tryptophan W Trp UGG 1.03 1.27 1.24 1.22 Yes
Tyrosine Y Tyr UAU, UAC 3.35 2.94 2.87 2.66 Conditionally
Stop codon - Term UAA, UAG, UGA†† ? ? ? N/A N/A

* 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[8].
** 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.[9]

Mass spectrometry[edit]

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.[10] In mass spectrometry, ions may also include one or more protons (Monoisotopic mass = 1.00728 Da; average mass = 1.0074 Da).

Amino acid Short Abbrev. Formula Mon. mass§ (Da) Avg. mass (Da)
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 147.06841 147.1739
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[edit]

The table below lists the abundance of amino acids in E.coli cells 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.[11] The abundance of amino acids includes amino acids in free form and in polymerization form (proteins).

Amino acid Abundance
(# of molecules (×108)
per E. coli cell)
ATP cost in synthesis
in aerobic
conditions
in anaerobic
conditions
Alanine 2.9 -1 1
Cysteine 0.52 11 15
Aspartic acid 1.4 0 2
Glutamic acid 1.5 -7 -1
Phenylalanine 1.1 -6 2
Glycine 3.5 -2 2
Histidine 0.54 1 7
Isoleucine 1.7 7 11
Lysine 2.0 5 9
Leucine 2.6 -9 1
Methionine 0.88 21 23
Asparagine 1.4 3 5
Proline 1.3 -2 4
Glutamine 1.5 -6 0
Arginine 1.7 5 13
Serine 1.2 -2 2
Threonine 1.5 6 8
Tryptophan 0.33 -7 7
Tyrosine 0.79 -8 2
Valine 2.4 -2 2

Remarks[edit]

Amino acid Abbrev. Remarks
Alanine A Ala Very abundant and very versatile, it is 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 Asp behaves similarly to glutamic acid, and carries a hydrophilic acidic group with strong negative charge. Usually, it is located on the outer surface of the protein, making it water-soluble. It binds to positively charged molecules and ions, and is 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 Glu behaves similarly to aspartic acid, and has a longer, slightly more flexible side chain.
Phenylalanine F Phe Essential for humans, phenylalanine, tyrosine, and tryptophan contain a 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, and 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 His is 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 Ile is 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 Lys is essential for humans, and behaves similarly to arginine. It 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 Leu is essential for humans, and behaves similarly to isoleucine and valine.
Methionine M Met Met is essential for humans. Always the first amino acid to be incorporated into a protein, it is sometimes removed after translation. Like cysteine, it 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, but it has a pyrroline ring attached.
Proline P Pro Pro contains an unusual ring to the N-end amine group, which forces the CO-NH amide sequence into a fixed conformation. It can disrupt protein folding structures like α helix or β sheet, forcing the desired kink in the protein chain. Common in collagen, it often undergoes a post-translational 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, it is 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, so the outer regions of soluble proteins tend to be rich with them.
Threonine T Thr Essential for humans, Thr behaves similarly to serine.
Selenocysteine U Sec The selenium analog of cysteine, in which selenium replaces the sulfur atom.
Valine V Val Essential for humans, Val behaves similarly to isoleucine and leucine.
Tryptophan W Trp Essential for humans, Trp behaves similarly to phenylalanine and tyrosine. It is a precursor of serotonin and is naturally fluorescent.
Unknown X Xaa Placeholder when the amino acid is unknown or unimportant.
Tyrosine Y Tyr Tyr behaves similarly to phenylalanine (precursor to tyrosine) and tryptophan, and is a precursor of melanin, epinephrine, and thyroid hormones. Naturally fluorescent, its 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

Catabolism[edit]

Amino acid catalobism

Amino acids can be classified according to the properties of their main products:[12]

  • Glucogenic, with the products having the ability to form glucose by gluconeogenesis
  • Ketogenic, with the products not having the ability to form glucose: These products may still be used for ketogenesis or lipid synthesis.
  • Amino acids catabolized into both glucogenic and ketogenic products

Life based on alternative proteinogenic sets[edit]

The proteinogenic set used by known life on Earth appears to be arbitrarily 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 experiments on artificial abiogenesis show that alpha-type amino acids predominate in water-based 'primordial soups', but beta-type amino acids dominate when less water is present. Both alpha- and beta-based sets could form the basis for alternative protein constructions and life forms.

See also[edit]

References[edit]

  1. ^ Ambrogelly A, Palioura S, Söll D (January 2007). "Natural expansion of the genetic code". Nature Chemical Biology. 3 (1): 29–35. doi:10.1038/nchembio847. PMID 17173027.
  2. ^ Lobanov AV, Turanov AA, Hatfield DL, Gladyshev VN (August 2010). "Dual functions of codons in the genetic code". Critical Reviews in Biochemistry and Molecular Biology. 45 (4): 257–65. doi:10.3109/10409231003786094. PMC 3311535. PMID 20446809.
  3. ^ Young VR (August 1994). "Adult amino acid requirements: the case for a major revision in current recommendations" (PDF). The Journal of Nutrition. 124 (8 Suppl): 1517S–1523S. doi:10.1093/jn/124.suppl_8.1517S. PMID 8064412.
  4. ^ Erives A (August 2011). "A model of proto-anti-codon RNA enzymes requiring L-amino acid homochirality". Journal of Molecular Evolution. 73 (1–2): 10–22. doi:10.1007/s00239-011-9453-4. PMC 3223571. PMID 21779963.
  5. ^ Thurlkill RL, Grimsley GR, Scholtz JM, Pace CN (May 2006). "pK values of the ionizable groups of proteins". Protein Science. 15 (5): 1214–8. doi:10.1110/ps.051840806. PMC 2242523. PMID 16597822.
  6. ^ Pace CN, Grimsley GR, Scholtz JM (May 2009). "Protein ionizable groups: pK values and their contribution to protein stability and solubility". The Journal of Biological Chemistry. 284 (20): 13285–9. doi:10.1074/jbc.R800080200. PMC 2679426. PMID 19164280.
  7. ^ Byun BJ, Kang YK (May 2011). "Conformational preferences and pK(a) value of selenocysteine residue". Biopolymers. 95 (5): 345–53. doi:10.1002/bip.21581. PMID 21213257.
  8. ^ Rother M, Krzycki JA (August 2010). "Selenocysteine, pyrrolysine, and the unique energy metabolism of methanogenic archaea". Archaea. 2010. doi:10.1155/2010/453642. PMC 2933860. PMID 20847933.
  9. ^ Kozlowski LP (January 2017). "Proteome-pI: proteome isoelectric point database". Nucleic Acids Research. 45 (D1): D1112–D1116. doi:10.1093/nar/gkw978. PMC 5210655. PMID 27789699.
  10. ^ "Atomic Weights and Isotopic Compositions for All Elements". NIST. Retrieved 2016-12-12.
  11. ^ Phillips R, Kondev J, Theriot J, Garcia HG, Orme N. Physical biology of the cell (Second ed.). Garland Science. p. 178. ISBN 978-0-8153-4450-6.
  12. ^ Ferrier DR. "Chapter 20: Amino Acid Degradation and Synthesis". In Champe PC, Harvey RA, Ferrier DR. Lippincott's Illustrated Reviews: Biochemistry (Lippincott's Illustrated Reviews). Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-2265-0.

General references[edit]

  • Nelson, David L.; Cox, Michael M. (2000). Lehninger Principles of Biochemistry (3rd ed.). Worth Publishers. ISBN 978-1-57259-153-0.
  • Kyte J, Doolittle RF (May 1982). "A simple method for displaying the hydropathic character of a protein". Journal of Molecular Biology. 157 (1): 105–32. 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.
  • Biochemistry, Harpers (2015). Harpers Illustrated Biochemistry (30st ed.). Lange. ISBN 978-0-07-182534-4.

External links[edit]