![Nonproteinogenic AAs](https://upload.wikimedia.org/wikipedia/commons/d/d8/Nonproteinogenic_AAs.svg)
In
biochemistry
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
, non-coded or non-proteinogenic
amino acids are distinct from the 22
proteinogenic amino acids
Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation (biology), translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (p ...
(21 in eukaryotes
[plus ]formylmethionine
''N''-Formylmethionine (fMet, HCO-Met, For-Met) is a derivative of the amino acid methionine in which a formyl group has been added to the amino group. It is specifically used for initiation of protein synthesis from bacterial and organellar g ...
in eukaryotes with prokaryote organelles like mitochondria) which are naturally encoded in the
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...
of organisms for the assembly of proteins. However, over 140 non-proteinogenic amino acids occur naturally in proteins and thousands more may occur in nature or be synthesized in the laboratory. Chemically synthesized amino acids can be called unnatural amino acids. Unnatural amino acids can be synthetically prepared from their native analogs via modifications such as amine alkylation, side chain substitution, structural bond extension cyclization, and isosteric replacements within the amino acid backbone.
Many non-proteinogenic amino acids are important:
* intermediates in biosynthesis,
* in post-translational formation of proteins,
* in a physiological role (e.g. components of
bacterial cell walls,
neurotransmitters
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neur ...
and
toxins),
* natural or man-made pharmacological compounds,
* present in meteorites or used in prebiotic experiments (such as the
Miller–Urey experiment
The Miller–Urey experiment (or Miller experiment) is a famous chemistry experiment that simulated the conditions thought at the time (1952) to be present in the atmosphere of the early, prebiotic Earth, in order to test the hypothesis of the ...
).
Definition by negation
![Lysine fisher structure and 3d ball](https://upload.wikimedia.org/wikipedia/commons/5/5f/Lysine_fisher_structure_and_3d_ball.svg)
Technically, any organic compound with an
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
(–NH
2) and a
carboxylic acid (–COOH)
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the re ...
is an amino acid. The proteinogenic amino acids are small subset of this group that possess central carbon atom (α- or 2-) bearing an amino group, a carboxyl group, a
side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a ...
and an α-hydrogen levo
conformation, with the exception of
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
, which is
achiral, and
proline, whose amine group is a secondary amine and is consequently frequently referred to as an
imino acid
In organic chemistry, an imino acid is any molecule that contains both imine (>C=NH) and carboxyl (-C(=O)-OH) functional groups.
Imino acids are structurally related to amino acids, which have amino group instead of imine—a difference of si ...
for traditional reasons, albeit not an imino.
The genetic code encodes 20 standard amino acids for incorporation into proteins during
translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
. However, there are two extra proteinogenic amino acids:
selenocysteine and
pyrrolysine. These non-standard amino acids do not have a dedicated codon, but are added in place of a stop codon when a specific sequence is present, UGA codon and
SECIS element
In biology, the SECIS element (SECIS: ''selenocysteine insertion sequence'') is an RNA element around 60 nucleotides in length that adopts a stem-loop structure. This structural motif (pattern of nucleotides) directs the cell to translate UGA ...
for selenocysteine, UAG
PYLIS downstream sequence
In biology, the PYLIS downstream sequence (PYLIS: ''pyrrolysine insertion sequence'') is a stem-loop structure that appears on some mRNA sequences. This structural motif was previously thought to cause the UAG (amber) stop codon to be translate ...
for pyrrolysine. All other amino acids are termed "non-proteinogenic".
L-selenocysteine-2D-skeletal.png, Selenocysteine. This amino acid contains a selenol group on its β-carbon
Pyrrolysine.svg, Pyrrolysine. This amino acid is formed by joining to the ε-amino group of lysine a carboxylated pyrroline ring
There are various groups of amino acids:
* 20 standard amino acids
* 22 proteinogenic amino acids
* over 80 amino acids created abiotically in high concentrations
* about 900 are produced by natural pathways
* over 118 engineered amino acids have been placed into protein
These groups overlap, but are not identical. All 22 proteinogenic amino acids are biosynthesised by organisms and some, but not all, of them also are abiotic (found in prebiotic experiments and meteorites). Some natural amino acids, such as
norleucine
Norleucine (abbreviated as Nle) is an amino acid with the formula CH3(CH2)3CH(NH2)CO2H. A systematic name for this compound is 2-aminohexanoic acid. The compound is an isomer of the more common amino acid leucine. Like most other α-amino acids ...
, are misincorporated translationally into proteins due to infidelity of the protein-synthesis process. Many amino acids, such as
ornithine
Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl.
Role in urea cycle
L-Ornithine is one of the produ ...
, are metabolic intermediates produced biosynthetically, but not incorporated translationally into proteins.
Post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
of amino acid residues in proteins leads to the formation of many proteinaceous, but non-proteinogenic, amino acids. Other amino acids are solely found in abiotic mixes (e.g. α-methylnorvaline). Over 30 unnatural amino acids have been inserted translationally into protein in engineered systems, yet are not biosynthetic.
Nomenclature
In addition to the
IUPAC numbering system to differentiate the various carbons in an organic molecule, by sequentially assigning a number to each carbon, including those forming a carboxylic group, the carbons along the side-chain of amino acids can also be labelled with Greek letters, where the
α-carbon
In the nomenclature of organic chemistry, a locant is a term to indicate the position of a functional group or substituent within a molecule.
Numeric locants
The International Union of Pure and Applied Chemistry (IUPAC) recommends the use of ...
is the central chiral carbon possessing a carboxyl group, a side chain and, in α-amino acids, an amino group – the carbon in carboxylic groups is not counted. (Consequently, the IUPAC names of many non-proteinogenic α-amino acids start with ''2-amino-'' and end in ''-ic acid''.)
Natural non-L-α-amino acids
Most natural amino acids are α-amino acids in the
L conformation, but some exceptions exist.
Non-alpha
Some non-α-amino acids exist in organisms. In these structures, the amine group displaced further from the carboxylic acid end of the amino acid molecule. Thus a β-amino acid has the amine group bonded to the second carbon away, and a γ-amino acid has it on the third. Examples include
β-alanine,
GABA, and δ-
aminolevulinic acid.
Beta-alanine structure.svg, β-alanine: an amino acid produced by aspartate 1-decarboxylase and a precursor to coenzyme A and the peptides carnosine
Carnosine (''beta''-alanyl-L-histidine) is a dipeptide molecule, made up of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues. Carnosine was discovered by Russian chemist Vladimir Gulevich.
Ca ...
and anserine
Anserine (β-alanyl-''3''-methylhistidine) is a dipeptide containing β-alanine and 3-methylhistidine. Anserine is a derivative of carnosine, which has been methylated. Both anserine and carnosine are capable of chelating copper. Due to its m ...
.
Gamma-Aminobuttersäure - gamma-aminobutyric acid.svg, γ-Aminobutyric acid (GABA): a neurotransmitter in animals.
Aminolevulinic_acid.svg, δ-Aminolevulinic acid: an intermediate in tetrapyrrole biosynthesis (haem
Heme, or haem (pronounced /Help:IPA/English, hi:m/ ), is a precursor (chemistry), precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, ...
, chlorophyll, cobalamin
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...
etc.).
4-Aminobenzoic_acid.svg, 4-Aminobenzoic acid (PABA): an intermediate in folate
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
biosynthesis
The reason why α-amino acids are used in proteins has been linked to their frequency in meteorites and prebiotic experiments.
An initial speculation on the deleterious properties of β-amino acids in terms of secondary structure
turned out to be incorrect.
D-amino acids
Some amino acids contain the opposite absolute chirality, chemicals that are not available from normal ribosomal translation and transcription machinery. Most bacterial cells walls are formed by
peptidoglycan
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...
, a polymer composed of amino sugars crosslinked with short oligopeptides bridged between each other. The oligopeptide is non-ribosomally synthesised and contains several peculiarities including
D-amino acid
D-Amino acids are amino acids where the stereogenic carbon alpha to the amino group has the D-configuration. For most naturally-occurring amino acids, this carbon has the L-configuration. D-Amino acids are occasionally found in nature as residue ...
s, generally
D-alanine and
D-glutamate. A further peculiarity is that the former is racemised by a
PLP-binding enzymes (encoded by ''alr'' or the homologue ''dadX''), whereas the latter is racemised by a cofactor independent enzyme (''murI''). Some variants are present, in ''
Thermotoga
''Thermotoga'' is a genus of the phylum ''Thermotogota''. Members of ''Thermotoga'' are hyperthermophilic bacteria whose cell is wrapped in a unique sheath-like outer membrane, called a "toga".
The members of the phylum stain Gram-negative as th ...
'' spp.
D-Lysine is present and in certain
vancomycin
Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...
-resistant bacteria
D-serine is present (''vanT'' gene).
Without a hydrogen on the α-carbon
All proteinogenic amino acids have at least one hydrogen on the α-carbon. Glycine has two hydrogens, and all others have one hydrogen and one side-chain. Replacement of the remaining hydrogen with a larger substituent, such as a methyl group, distorts the protein backbone.
In some fungi
α-aminoisobutyric acid is produced as a precursor to peptides, some of which exhibit antibiotic properties. This compound is similar to alanine, but possesses an additional methyl group on the α-carbon instead of a hydrogen. It is therefore achiral. Another compound similar to alanine without an α-hydrogen is
dehydroalanine
Dehydroalanine (Cα,β-didehydroalanine, α,β-di-dehydroalanine, 2-aminoacrylate, or 2,3-didehydroalanine) is a dehydroamino acid. It does not exist in its free form, but it occurs naturally as a residue found in peptides of microbial origin. As ...
, which possess a methylene sidechain. It is one of several naturally occurring
dehydroamino acid
In biochemistry, a dehydroamino acid is an amino acids, usually with a C=C double bond in its side chain. Dehydroamino acids are not coded by DNA, but arise via post-transcriptional modification.
Examples
A common dehydroamino acid is dehydroal ...
s.
L-Alanin - L-Alanine.svg, alanine
2-aminoisobutyric acid.svg, aminoisobutyric acid
Dehydroalanin.svg, dehydroalanine
Twin amino acid stereocentres
A subset of
L-α-amino acids are ambiguous as to which of two ends is the α-carbon. In proteins a
cysteine residue can form a disulfide bond with another cysteine residue, thus crosslinking the protein. Two crosslinked cysteines form a
cystine
Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...
molecule. Cysteine and methionine are generally produced by direct sulfurylation, but in some species they can be produced by
transsulfuration
The transsulfuration pathway is a metabolic pathway involving the interconversion of cysteine and homocysteine through the intermediate cystathionine. Two transsulfurylation pathways are known: the ''forward'' and the ''reverse''.
The ''forward p ...
, where the activated
homoserine
Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2OH. -Homoserine is not one of the common amino acids encoded by DNA. It differs from the proteinogenic amino acid serine by insertion of an additi ...
or
serine is fused to a
cysteine or
homocysteine
Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In th ...
forming
cystathionine
Cystathionine is an intermediate in the synthesis of cysteine.
Cystathionine is produced by the transsulfuration pathway which converts homocysteine into cystathionine. Cystathionine is then used by the enzymes cystathionine gamma-lyase (CTH), ...
. A similar compound is
lanthionine
Lanthionine is a nonproteinogenic amino acid with the chemical formula (HOOC-CH(NH2)-CH2-S-CH2-CH(NH2)-COOH). It is typically formed by a cysteine residue and a dehydrated serine residue. Despite its name, lanthionine does not contain the element ...
, which can be seen as two alanine molecules joined via a thioether bond and is found in various organisms. Similarly,
djenkolic acid
Djenkolic acid (or sometimes jengkolic acid) is a sulfur-containing non-protein amino acid naturally found in the djenkol beans of the Southeast Asian plant '' Archidendron jiringa''. Its chemical structure is similar to cystine but contains a met ...
, a plant toxin from
jengkol beans, is composed of two cysteines connected by a methylene group.
Diaminopimelic acid
Diaminopimelic acid (DAP) is an amino acid, representing an epsilon-carboxy derivative of lysine.
DAP is a characteristic of certain cell walls of some bacteria. DAP is often found in the peptide linkages of NAM-NAG chains that make up the ce ...
is both used as a bridge in peptidoglycan and is used a precursor to lysine (via its decarboxylation).
Cystine-skeletal.png, cystine
Cystathionin.svg, cystathionine
Lanthionin.svg, lanthionine
Djenkolic acid.svg, djenkolic acid
Diaminopimelic acid.svg, diaminopimelic acid
Prebiotic amino acids and alternative biochemistries
In meteorites and in prebiotic experiments (e.g.
Miller–Urey experiment
The Miller–Urey experiment (or Miller experiment) is a famous chemistry experiment that simulated the conditions thought at the time (1952) to be present in the atmosphere of the early, prebiotic Earth, in order to test the hypothesis of the ...
) many more amino acids than the twenty standard amino acids are found, several of which at higher concentrations than the standard ones: it has been conjectured that if amino acid based life were to arise in parallel elsewhere in the universe, no more than 75% of the amino acids would be in common.
The most notable anomaly is the lack of aminobutyric acid.
Straight side chain
The genetic code has been described as a frozen accident and the reasons why there is only one standard amino acid with a straight chain (alanine) could simply be redundancy with valine, leucine and isoleucine.
However, straight chained amino acids are reported to form much more stable alpha helices.
Glycin - Glycine.svg, glycine (hydrogen side-chain)
L-Alanin - L-Alanine.svg, alanine (methyl side-chain)
Alpha-aminobutyric acid.png, homoalanine, or α-aminobutyric acid (ethyl side-chain)
L-Norvalin.svg, norvaline (''n''-propyl side-chain)
L-Norleucin.svg, norleucine (''n''-butyl side-chain)
Heptanoic acid.png, homonorleucine (''n''-Pentyl side-chain, heptanoic acid shown)
Chalcogen
Serine,
homoserine
Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2OH. -Homoserine is not one of the common amino acids encoded by DNA. It differs from the proteinogenic amino acid serine by insertion of an additi ...
, ''O''-methylhomoserine and ''O''-ethylhomoserine possess a hydroxymethyl, hydroxyethyl, ''O''-methylhydroxymethyl and ''O''-methylhydroxyethyl side chain; whereas cysteine,
homocysteine
Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In th ...
, methionine and
ethionine possess the thiol equivalents. The selenol equivalents are selenocysteine, selenohomocysteine, selenomethionine and selenoethionine. Amino acids with the next chalcogen down are also found in nature: several species such as ''
Aspergillus fumigatus'', ''
Aspergillus terreus
''Aspergillus terreus'', also known as ''Aspergillus terrestris'', is a fungus (mold) found worldwide in soil. Although thought to be strictly asexual until recently, ''A. terreus'' is now known to be capable of sexual reproduction. This saprotr ...
'', and ''
Penicillium chrysogenum
''Penicillium chrysogenum'' (formerly known as ''Penicillium notatum'') is a species of fungus in the genus ''Penicillium''. It is common in temperate and subtropical regions and can be found on salted food products, but it is mostly found in in ...
'' in the absence of sulfur are able to produce and incorporate into protein
tellurocysteine
Tellurocysteine (in some publications referred to as Te-Cys) is an amino acid analogous to serine, cysteine and selenocysteine with tellurium in place of oxygen, sulfur or selenium in its side chain. It is not naturally found in organisms.
Proper ...
and telluromethionine.
Expanded genetic code
Roles
In cells, especially autotrophs, several non-proteinogenic amino acids are found as metabolic intermediates. However, despite the catalytic flexibility of PLP-binding enzymes, many amino acids are synthesised as
keto acids
Keto may refer to:
* The Ket people (also known as Кето), an ethnic group of the Siberian North
* Ceto or Keto, a sea goddess in Greek mythology
* Ketone or keto group, the functional group in the chemical compounds ketones
* Ketoconazole, a m ...
(such as 4-methyl-2-oxopentanoate to leucine) and aminated in the last step, thus keeping the number of non-proteinogenic amino acid intermediates fairly low.
Ornithine
Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl.
Role in urea cycle
L-Ornithine is one of the produ ...
and
citrulline
The organic compound citrulline is an α-amino acid. Its name is derived from ''citrullus'', the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in 1 ...
occur in the
urea cycle
The urea cycle (also known as the ornithine cycle) is a cycle of Biochemistry, biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic.
The urea cycle ...
, part of amino acid
catabolism (see below).
In addition to
primary metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
, several non-proteinogenic amino acids are precursors or the final production in
secondary metabolism
Secondary metabolism (also called specialized metabolism) is a term for pathways and small molecule products of metabolism that are involved in ecological interactions, but are not absolutely required for the survival of the organism. These molecu ...
to make small compounds or
non-ribosomal peptides (such as some
toxins).
Post-translationally incorporated into protein
Despite not being encoded by the genetic code as proteinogenic amino acids, some non-standard amino acids are nevertheless found in proteins. These are formed by
post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
of the side chains of standard amino acids present in the target protein. These modifications are often essential for the function or regulation of a protein; for example, in
γ-carboxyglutamate
Carboxyglutamic acid (or the conjugate base, carboxyglutamate), is an uncommon amino acid introduced into proteins by a post-translational carboxylation of glutamic acid residues. This modification is found, for example, in clotting factors and ...
the
carboxylation
Carboxylation is a chemical reaction in which a carboxylic acid is produced by treating a substrate with carbon dioxide. The opposite reaction is decarboxylation. In chemistry, the term carbonation is sometimes used synonymously with carboxylatio ...
of
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
allows for better binding of
calcium cations, and in
hydroxyproline
(2''S'',4''R'')-4-Hydroxyproline, or L-hydroxyproline ( C5 H9 O3 N), is an amino acid, abbreviated as Hyp or O, ''e.g.'', in Protein Data Bank.
Structure and discovery
In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelati ...
the
hydroxylation of
proline is critical for maintaining
connective tissues
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tissue is ...
. Another example is the formation of
hypusine
Hypusine is an uncommon amino acid found in all eukaryotes and in some archaea, but not in bacteria. The only known proteins containing the hypusine residue is eukaryotic translation initiation factor 5A (eIF-5A) and a similar protein found in ...
in the
translation initiation factor Initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis.
Initiation factors can interact with repressors to slow down or prevent translation. They have the ...
EIF5A
Eukaryotic translation initiation factor 5A-1 is a protein that in humans is encoded by the ''EIF5A'' gene.
It is the only known protein to contain the unusual amino acid hypusine 'N''ε-(4-amino-2-hydroxybutyl)-lysine which is synthesized on e ...
, through modification of a lysine residue. Such modifications can also determine the localization of the protein, for example, the addition of long hydrophobic groups can cause a protein to bind to a
phospholipid membrane.
Carboxyglutamic_acid.png, Carboxyglutamic acid. Whereas glutamic acid possess one γ-carboxyl group, Carboxyglutamic acid possess two.
Hydroxyproline structure.svg, Hydroxyproline. This imino acid differs from proline due to a hydroxyl group on carbon 4.
Hypusine natural.svg, Hypusine
Hypusine is an uncommon amino acid found in all eukaryotes and in some archaea, but not in bacteria. The only known proteins containing the hypusine residue is eukaryotic translation initiation factor 5A (eIF-5A) and a similar protein found in ...
. This amino acid is obtained by adding to the ε-amino group of a lysine a 4-aminobutyl moiety (obtained from spermidine
Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen.
Function
Spermidine is an aliphatic polyamine. Spermidine synthase (SP ...
)
(S)-Pyroglutamic_acid_Structural_Formulae.png, Pyroglutamic acid
Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but little studied natural amino acid derivative in which the free amino group of glutamic acid or glutamine cyclizes to form a lactam. The names of pyroglutamic ac ...
There is some preliminary evidence that
aminomalonic acid may be present, possibly by misincorporation, in protein.
Toxic analogues
Several non-proteinogenic amino acids are toxic due to their ability to mimic certain properties of proteinogenic amino acids, such as
thialysine. Some non-proteinogenic amino acids are neurotoxic by mimicking amino acids used as neurotransmitters (that is, not for protein biosynthesis), including
quisqualic acid
Quisqualic acid is an agonist of the AMPA, kainate, and group I metabotropic glutamate receptors. It is one of the most potent AMPA receptor agonists known. It causes excitotoxicity and is used in neuroscience to selectively destroy neurons in ...
,
canavanine and
azetidine-2-carboxylic acid
Azetidine-2-carboxylic acid (abbreviated Aze) is a plant Non-proteinogenic amino acids, non-protein amino acid homologue of proline with the molecular formula C4H7NO2. Aze is a heterocyclic, 4 membered ring with nitrogen as its heteroatom (an azet ...
.
Cephalosporin C
Cephalosporin C is an antibiotic of the cephalosporin class. It was isolated from a fungus of the genus ''Acremonium'' and first characterized in 1961. Although not a very active antibiotic itself, synthetic analogs of cephalosporin C, such as ce ...
has an α-aminoadipic acid (homoglutamate) backbone that is amidated with a cephalosporin moiety.
Penicillamine
Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have high urine cystine levels, rheumatoid arthritis, ...
is a therapeutic amino acid, whose mode of action is unknown.
Thialysine.png, Thialysine
Quisqualic acid.svg, quisqualic acid
L-S-Canavanine.svg, canavanine
S-(-)-Azetidine-2-carboxylate.png, azetidine-2-carboxylic acid
Cephalosporin C.svg, cephalosporin C
Penicillamine structure.png, penicillamine
Naturally-occurring
cyanotoxin
Cyanotoxins are toxins produced by cyanobacteria (also known as blue-green algae). Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they exponential gr ...
s can also include non-proteinogenic amino acids.
Microcystin
Microcystins—or cyanoginosins—are a class of toxins produced by certain freshwater cyanobacteria, commonly known as blue-green algae. Over 250 different microcystins have been discovered so far, of which microcystin-LR is the most common. Che ...
and
nodularin
Nodularins are potent toxins produced by the cyanobacterium '' Nodularia spumigena'', among others. This aquatic, photosynthetic cyanobacterium forms visible colonies that present as algal blooms in brackish water bodies throughout the world. The ...
, for example, are both derived from
ADDA, a β-amino acid.
Not amino acids
Taurine
Taurine (), or 2-aminoethanesulfonic acid, is an organic compound that is widely distributed in animal tissues. It is a major constituent of bile and can be found in the large intestine, and accounts for up to 0.1% of total human body weight. I ...
is an
amino sulfonic acid
In chemistry, amines (, ) are chemical compound, compounds and functional groups that contain a base (chemistry), basic nitrogen atom with a lone pair. Amines are formally derivative (chemistry), derivatives of ammonia (), wherein one or mo ...
and not an amino carboxylic acid, however it is occasionally considered as such as the amounts required to suppress the
auxotroph
Auxotrophy ( grc, αὐξάνω "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this ...
in certain organisms (such as cats) are closer to those of "essential amino acids" (amino acid auxotrophy) than of vitamins (cofactor auxotrophy).
The osmolytes,
sarcosine
Sarcosine, also known as ''N''-methylglycine, or monomethylglycine, is a monopeptide with the formula CH3N(H)CH2CO2H. It exists at neutral pH as the zwitterion CH3N+(H)2CH2CO2−, which can be obtained as a white, water-soluble powder. Like som ...
and
glycine betaine
Trimethylglycine is an amino acid derivative that occurs in plants. Trimethylglycine was the first betaine discovered; originally it was simply called betaine because, in the 19th century, it was discovered in sugar beets. It has a sweet and umami ...
are derived from amino acids, but have a secondary and quaternary amine respectively.
Notes
References
{{Non-proteinogenic amino acids
Amino acids