Proteinogenic amino acid

Proteinogenic amino acids are a small fraction of all amino acids

Proteinogenic amino acids are amino acids that are precursors to proteins, and are incorporated into proteins during translation.^[1] Throughout known life, there are 23 proteinogenic amino acids, 20 in the standard genetic code and an additional 3 that can be incorporated by special translation mechanisms.

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 bacteria, the AUG initiation codon is translated to N-formylmethionine when it is actually used to initiate translation and translated normally (to methionine) at other times.^[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 word "proteinogenic" means "protein creating". 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 post-translational 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 autoaminoacylation systems.^[4] Thus, nonproteinogenic 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 nonproteinogenic 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.

Nonproteinogenic amino acids are incorporated in nonribosomal peptides, which are not produced by the ribosome during translation.

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.

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

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

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

• 
  L-Selenocysteine
  (Sec / U)
• 
  L-Pyrrolysine
  (Pyl / O)

Nonspecific abbreviations

Sometimes, the specific identity of an amino acid cannot be determined unambiguously. Certain protein sequencing techniques do not distinguish among certain pairs. Thus, these 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.

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, so the mass of an amino acid unit within a protein chain is reduced by 18.01524 Da.

General chemical properties

Side chain properties

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

* 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.
& Occurrence of amino acids is based on 135 Archaea, 3775 Bacteria, 614 Eukaryota proteomes and human proteome (21 006 proteins) respectively.^[5]

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.^[6]

§ 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 the amino acids. Negative numbers indicate the metabolic processes are energy favorable and do not cost net ATP of the cell.^[7] The abundance of amino acids includes amino acids in free form and in polymerization form (proteins).

Remarks

Catabolism

Amino acids can be classified according to the properties of their main products as either of:^[8]

• 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

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

• Glucogenic amino acid
• Ketogenic amino acid

References

General references

• 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. 
• Biochemistry, Harpers (2015). Harpers Illustrated Biochemistry (30st ed.). Lange. ISBN 978-0-07-182534-4. 

External links

Wikimedia Commons has media related to Amino acids.

• The origin of the single-letter code for the amino acids

The encoded amino acid
General topics	Protein Peptide Genetic code
By properties	Aliphatic Branched-chain amino acids (Valine Isoleucine Leucine) Methionine Alanine Proline Glycine Aromatic Phenylalanine Tyrosine Tryptophan Histidine Polar, uncharged Asparagine Glutamine Serine Threonine Positive charge (pKa) Lysine (≈10.8) Arginine (≈12.5) Histidine (≈6.1) Negative charge (pKa) Aspartic acid (≈3.9) Glutamic acid (≈4.1) Cysteine (≈8.3) Tyrosine (≈10.1)
Other classifications	Essential amino acid Ketogenic amino acid Glucogenic amino acid Non-proteinogenic amino acid