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Amino acids are that contain both amino and carboxylic acid . Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into . Only these 22 appear in the genetic code of life.
Amino acids can be classified according to the locations of the core structural functional groups ( amino acids, etc.); other categories relate to polarity, ionization, and side-chain group type (aliphatic, acyclic, aromatic, polar, etc.). In the form of proteins, amino-acid residues form the second-largest component (water being the largest) of human and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in abiogenesis.
Amino acids are formally named by the IUPAC-IUBMB Joint Commission on Biochemical Nomenclature in terms of the fictitious "neutral" structure shown in the illustration. For example, the systematic name of alanine is 2-aminopropanoic acid, based on the formula . The Commission justified this approach as follows:
The systematic names and formulas given refer to hypothetical forms in which amino groups are unprotonated and carboxyl groups are undissociated. This convention is useful to avoid various nomenclatural problems but should not be taken to imply that these structures represent an appreciable fraction of the amino-acid molecules.
The unity of the chemical category was recognized by Wurtz in 1865, but he gave no particular name to it.Menten, P. Dictionnaire de chimie: Une approche étymologique et historique. De Boeck, Bruxelles. link . The first use of the term "amino acid" in the English language dates from 1898, while the German term, Aminosäure, was used earlier. were found to yield amino acids after enzymatic digestion or acid hydrolysis. In 1902, Emil Fischer and Franz Hofmeister independently proposed that proteins are formed from many amino acids, whereby bonds are formed between the amino group of one amino acid with the carboxyl group of another, resulting in a linear structure that Fischer termed "peptide".
Of the many hundreds of described amino acids, 22 are proteinogenic ("protein-building"). (2024). 9781617793318, Humana Press. ISBN 9781617793318
It is these 22 compounds that combine to give a vast array of peptides and proteins assembled by . Non-proteinogenic or modified amino acids may arise from post-translational modification or during nonribosomal peptide synthesis.
A few D-amino acids ("right-handed") have been found in nature, e.g., in bacterial envelopes, as a Neuromodulation (D-serine), and in some . (2024). 9780470146842, Wiley-Blackwell. ISBN 9780470146842 Rarely, D-Amino acid are found in proteins, and are converted from the L-amino acid as a post-translational modification.
The two negatively charged amino acids at neutral pH are Aspartic acid (Asp, D) and Glutamic acid (Glu, E). The anionic carboxylate groups behave as Brønsted bases in most circumstances. Enzymes in very low pH environments, like the aspartic protease pepsin in mammalian stomachs, may have catalytic aspartate or glutamate residues that act as Brønsted acids.
There are three amino acids with side chains that are cations at neutral pH: arginine (Arg, R), lysine (Lys, K) and histidine (His, H). Arginine has a charged Guanidine group and lysine a charged alkyl amino group, and are fully protonated at pH 7. Histidine's imidazole group has a pKa of 6.0, and is only around 10% protonated at neutral pH. Because histidine is easily found in its basic and conjugate acid forms it often participates in catalytic proton transfers in enzyme reactions.
In strongly acidic conditions (pH below 3), the carboxylate group becomes protonated and the structure becomes an ammonio carboxylic acid, . This is relevant for enzymes like pepsin that are active in acidic environments such as the mammalian stomach and lysosomes, but does not significantly apply to intracellular enzymes. In highly basic conditions (pH greater than 10, not normally seen in physiological conditions), the ammonio group is deprotonated to give .
Although various definitions of acids and bases are used in chemistry, the only one that is useful for chemistry in aqueous solution is that of Brønsted: an acid is a species that can donate a proton to another species, and a base is one that can accept a proton. This criterion is used to label the groups in the above illustration. The carboxylate side chains of aspartate and glutamate residues are the principal Brønsted bases in proteins. Likewise, lysine, tyrosine and cysteine will typically act as a Brønsted acid. Histidine under these conditions can act both as a Brønsted acid and a base.
For amino acids with charged side chains, the p Ka of the side chain is involved. Thus for aspartate or glutamate with negative side chains, the terminal amino group is essentially entirely in the charged form , but this positive charge needs to be balanced by the state with just one C-terminal carboxylate group is negatively charged. This occurs halfway between the two carboxylate p Ka values: p I = (p Ka1 + p Ka(R)), where p Ka(R) is the side chain p Ka.
Similar considerations apply to other amino acids with ionizable side-chains, including not only glutamate (similar to aspartate), but also cysteine, histidine, lysine, tyrosine and arginine with positive side chains.
Amino acids have zero mobility in electrophoresis at their isoelectric point, although this behaviour is more usually exploited for peptides and proteins than single amino acids. Zwitterions have minimum solubility at their isoelectric point, and some amino acids (in particular, with nonpolar side chains) can be isolated by precipitation from water by adjusting the pH to the required isoelectric point.
Some amino acids have special properties. Cysteine can form covalent to other cysteine residues. Proline forms cyclic compound to the polypeptide backbone, and glycine is more flexible than other amino acids.
Glycine and proline are strongly present within low complexity regions of both eukaryotic and prokaryotic proteins, whereas the opposite is the case with cysteine, phenylalanine, tryptophan, methionine, valine, leucine, isoleucine, which are highly reactive, or complex, or hydrophobic.
Many proteins undergo a range of posttranslational modifications, whereby additional chemical groups are attached to the amino acid residue side chains sometimes producing (that are hydrophobic), or (that are hydrophilic) allowing the protein to attach temporarily to a membrane. For example, a signaling protein can attach and then detach from a cell membrane, because it contains cysteine residues that can have the fatty acid palmitic acid added to them and subsequently removed.
The one-letter notation was chosen by IUPAC-IUB based on the following rules:
| Alanine | Ala | A | Aliphatic | Nonpolar | Neutral | 1.8 | 89.094 | 8.76 | GCN | ||
| Arginine | Arg | R | Fixed cation | Basic polar | Positive | −4.5 | 174.203 | 5.78 | MGR, CGYCodons can also be expressed by: CGN, AGR | ||
| Asparagine | Asn | N | Amide | Polar | Neutral | −3.5 | 132.119 | 3.93 | AAY | ||
| Aspartate | Asp | D | Anion | Brønsted base | Negative | −3.5 | 133.104 | 5.49 | GAY | ||
| Cysteine | Cys | C | Thiol | Brønsted acid | Neutral | 2.5 | 250 | 0.3 | 121.154 | 1.38 | UGY |
| Glutamine | Gln | Q | Amide | Polar | Neutral | −3.5 | 146.146 | 3.9 | CAR | ||
| Glutamate | Glu | E | Anion | Brønsted base | Negative | −3.5 | 147.131 | 6.32 | GAR | ||
| Glycine | Gly | G | Aliphatic | Nonpolar | Neutral | −0.4 | 75.067 | 7.03 | GGN | ||
| Histidine | His | H | Cationic | Brønsted acid and base | Positive, 10% Neutral, 90% | −3.2 | 211 | 5.9 | 155.156 | 2.26 | CAY |
| Isoleucine | Ile | I | Aliphatic | Nonpolar | Neutral | 4.5 | 131.175 | 5.49 | AUH | ||
| Leucine | Leu | L | Aliphatic | Nonpolar | Neutral | 3.8 | 131.175 | 9.68 | YUR, CUYcodons can also be expressed by: CUN, UUR | ||
| Lysine | Lys | K | Cation | Brønsted acid | Positive | −3.9 | 146.189 | 5.19 | AAR | ||
| Methionine | Met | M | Thioether | Nonpolar | Neutral | 1.9 | 149.208 | 2.32 | AUG | ||
| Phenylalanine | Phe | F | Aromatic | Nonpolar | Neutral | 2.8 | 257, 206, 188 | 0.2, 9.3, 60.0 | 165.192 | 3.87 | UUY |
| Proline | Pro | P | Cyclic | Nonpolar | Neutral | −1.6 | 115.132 | 5.02 | CCN | ||
| Serine | Ser | S | Hydroxylic | Polar | Neutral | −0.8 | 105.093 | 7.14 | UCN, AGY | ||
| Threonine | Thr | T | Hydroxylic | Polar | Neutral | −0.7 | 119.119 | 5.53 | ACN | ||
| Tryptophan | Trp | W | Aromatic | Nonpolar | Neutral | −0.9 | 280, 219 | 5.6, 47.0 | 204.228 | 1.25 | UGG |
| Tyrosine | Tyr | Y | Aromatic | Brønsted acid | Neutral | −1.3 | 274, 222, 193 | 1.4, 8.0, 48.0 | 181.191 | 2.91 | UAY |
| Valine | Val | V | Aliphatic | Nonpolar | Neutral | 4.2 | 117.148 | 6.73 | GUN |
Two additional amino acids are in some species coded for by codons that are usually interpreted as :
| Selenocysteine | Sec | U | 168.064 |
| Pyrrolysine | Pyl | O | 255.313 |
In addition to the specific amino acid codes, placeholders are used in cases where chemical or crystallographic analysis of a peptide or protein cannot conclusively determine the identity of a residue. They are also used to summarize conserved protein sequence motifs. The use of single letters to indicate sets of similar residues is similar to the use of abbreviation codes for degenerate bases.
| Any / unknown | Xaa | X | All | NNN |
| Asparagine or aspartate | Asx | B | D, N | RAY |
| Glutamine or glutamate | Glx | Z | E, Q | SAR |
| Leucine or isoleucine | Xle | J | I, L | YTR, ATH, CTYCodons can also be expressed by: CTN, ATH, TTR; MTY, YTR, ATA; MTY, HTA, YTG |
| Hydrophobic | Φ | V, I, L, F, W, Y, M | NTN, TAY, TGG | |
| Aromatic | Ω | F, W, Y, H | YWY, TTY, TGGCodons can also be expressed by: TWY, CAY, TGG | |
| Aliphatic (non-aromatic) | Ψ | V, I, L, M | VTN, TTRCodons can also be expressed by: NTR, VTY | |
| Small | π | P, G, A, S | BCN, RGY, GGR | |
| Hydrophilic | ζ | S, T, H, N, Q, E, D, K, R | VAN, WCN, CGN, AGYCodons can also be expressed by: VAN, WCN, MGY, CGP | |
| Cation | + | K, R, H | ARR, CRY, CGR | |
| Anion | − | D, E | GAN |
Unk is sometimes used instead of Xaa, but is less standard.
Ter or * (from termination) is used in notation for mutations in proteins when a stop codon occurs. It corresponds to no amino acid at all.
In addition, many nonstandard amino acids have a specific code. For example, several peptide drugs, such as Bortezomib and MG132, are artificially synthesized and retain their , which have specific codes. Bortezomib is pyrazinoic acid–Phe–boroLeu, and MG132 is Carboxybenzyl–Leu–Leu–Leu–al. To aid in the analysis of protein structure, photo-reactive amino acid analogs are available. These include photoleucine ( pLeu) and photomethionine ( pMet).
Twenty-two amino acids are naturally incorporated into polypeptides and are called proteinogenic or natural amino acids. Of these, 20 are encoded by the universal genetic code. The remaining 2, selenocysteine and pyrrolysine, are incorporated into proteins by unique synthetic mechanisms. Selenocysteine is incorporated when the mRNA being translated includes a SECIS element, which causes the UGA codon to encode selenocysteine instead of a stop codon. Pyrrolysine is used by some archaea in enzymes that they use to produce methane. It is coded for with the codon UAG, which is normally a stop codon in other organisms.
Several independent evolutionary studies have suggested that Gly, Ala, Asp, Val, Ser, Pro, Glu, Leu, Thr may belong to a group of amino acids that constituted the early genetic code, whereas Cys, Met, Tyr, Trp, His, Phe may belong to a group of amino acids that constituted later additions of the genetic code.
The two nonstandard proteinogenic amino acids are selenocysteine (present in many non-eukaryotes as well as most eukaryotes, but not coded directly by DNA) and pyrrolysine (found only in some archaea and at least one bacterium). The incorporation of these nonstandard amino acids is rare. For example, 25 human proteins include selenocysteine in their primary structure, and the structurally characterized enzymes (selenoenzymes) employ selenocysteine as the catalytic moiety in their active sites. Pyrrolysine and selenocysteine are encoded via variant codons. For example, selenocysteine is encoded by stop codon and SECIS element.
N-formylmethionine (which is often the initial amino acid of proteins in bacteria, Mitochondrion, and ) is generally considered as a form of methionine rather than as a separate proteinogenic amino acid. Codon–transfer RNA combinations not found in nature can also be used to "expand" the genetic code and form novel proteins known as incorporating non-proteinogenic amino acids.
Non-proteinogenic amino acids that are found in proteins are formed by post-translational modification. Such modifications can also determine the localization of the protein, e.g., the addition of long hydrophobic groups can cause a protein to bind to a phospholipid membrane. Examples:
Some non-proteinogenic amino acids are not found in proteins. Examples include 2-aminoisobutyric acid and the neurotransmitter gamma-aminobutyric acid. Non-proteinogenic amino acids often occur as intermediates in the metabolic pathways for standard amino acids – for example, ornithine and citrulline occur in the urea cycle, part of amino acid catabolism (see below). A rare exception to the dominance of α-amino acids in biology is the β-amino acid beta alanine (3-aminopropanoic acid), which is used in plants and microorganisms in the synthesis of pantothenic acid (vitamin B5), a component of coenzyme A.
Of the 20 standard amino acids, nine (Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan and Valine) are called essential amino acids because the human body cannot biosynthesis them from other compounds at the level needed for normal growth, so they must be obtained from food.
Amino acids are used in the synthesis of some cosmetics.
Nonstandard amino acids are usually formed through modifications to standard amino acids. For example, homocysteine is formed through the transsulfuration pathway or by the demethylation of methionine via the intermediate metabolite S-adenosylmethionine, while hydroxyproline is made by a post translational modification of proline.
and plants synthesize many uncommon amino acids. For example, some microbes make 2-aminoisobutyric acid and lanthionine, which is a sulfide-bridged derivative of alanine. Both of these amino acids are found in peptidic lantibiotics such as alamethicin. However, in plants, 1-aminocyclopropane-1-carboxylic acid is a small disubstituted cyclic amino acid that is an intermediate in the production of the plant hormone ethylene.
In the famous Urey-Miller experiment, the passage of an electric arc through a mixture of methane, hydrogen, and ammonia produces a large number of amino acids. Since then, scientists have discovered a range of ways and components by which the potentially prebiotic formation and chemical evolution of peptides may have occurred, such as condensing agents, the design of self-replicating peptides and a number of non-enzymatic mechanisms by which amino acids could have emerged and elaborated into peptides. Several hypotheses invoke the Strecker synthesis whereby hydrogen cyanide, simple aldehydes, ammonia, and water produce amino acids.
According to a review, amino acids, and even peptides, "turn up fairly regularly in the primordial soup that have been allowed to be cooked from simple chemicals. This is because are far more difficult to synthesize chemically than amino acids." For a chronological order, it suggests that there must have been a 'protein world' or at least a 'polypeptide world', possibly later followed by the 'RNA world' and the 'DNA world'. Codon–amino acids mappings may be the biology information system at the primordial origin of life on Earth. While amino acids and consequently simple peptides must have formed under different experimentally probed geochemical scenarios, the transition from an abiotic world to the first life forms is to a large extent still unresolved.
However, not all peptide bonds are formed in this way. In a few cases, peptides are synthesized by specific enzymes. For example, the tripeptide glutathione is an essential part of the defenses of cells against oxidative stress. This peptide is synthesized in two steps from free amino acids. In the first step, gamma-glutamylcysteine synthetase condenses cysteine and glutamate through a peptide bond formed between the side chain carboxyl of the glutamate (the gamma carbon of this side chain) and the amino group of the cysteine. This dipeptide is then condensed with glycine by glutathione synthetase to form glutathione.
In chemistry, peptides are synthesized by a variety of reactions. One of the most-used in solid-phase peptide synthesis uses the aromatic oxime derivatives of amino acids as activated units. These are added in sequence onto the growing peptide chain, which is attached to a solid resin support. Libraries of peptides are used in drug discovery through high-throughput screening.
The combination of functional groups allow amino acids to be effective polydentate ligands for metal–amino acid chelates.
The multiple side chains of amino acids can also undergo chemical reactions.
Degradation of an amino acid often involves deamination by moving its amino group to α-ketoglutarate, forming glutamate. This process involves transaminases, often the same as those used in amination during synthesis. In many vertebrates, the amino group is then removed through the urea cycle and is excreted in the form of urea. However, amino acid degradation can produce uric acid or ammonia instead. For example, serine dehydratase converts serine to pyruvate and ammonia. After removal of one or more amino groups, the remainder of the molecule can sometimes be used to synthesize new amino acids, or it can be used for energy by entering glycolysis or the citric acid cycle, as detailed in image at right.
Aspirational uses
Fertilizer
The Chelation ability of amino acids is sometimes used in fertilizers to facilitate the delivery of minerals to plants in order to correct mineral deficiencies, such as iron chlorosis. These fertilizers are also used to prevent deficiencies from occurring and to improve the overall health of the plants.
Biodegradable plastics
Amino acids have been considered as components of biodegradable polymers, which have applications as environmentally friendly packaging and in medicine in drug delivery and the construction of prosthetic implants. An interesting example of such materials is polyaspartate, a water-soluble biodegradable polymer that may have applications in disposable and agriculture. Due to its solubility and ability to chelate metal ions, polyaspartate is also being used as a biodegradable antiFouling agent and a corrosion inhibitor.
Synthesis
Chemical synthesis
The commercial production of amino acids usually relies on mutant bacteria that overproduce individual amino acids using glucose as a carbon source. Some amino acids are produced by enzymatic conversions of synthetic intermediates. 2-Aminothiazoline-4-carboxylic acid is an intermediate in one industrial synthesis of cysteine for example. Aspartic acid is produced by the addition of ammonia to fumarate using a lyase.
Biosynthesis
In plants, nitrogen is first assimilated into organic compounds in the form of glutamate, formed from alpha-ketoglutarate and ammonia in the mitochondrion. For other amino acids, plants use to move the amino group from glutamate to another alpha-keto acid. For example, aspartate aminotransferase converts glutamate and oxaloacetate to alpha-ketoglutarate and aspartate. Other organisms use transaminases for amino acid synthesis, too.
(1998). 9780470123188 ISBN 9780470123188
Primordial synthesis
The formation of amino acids and peptides are assumed to precede and perhaps induce the abiogenesis. Amino acids can form from simple precursors under various conditions. Surface-based chemical metabolism of amino acids and very small compounds may have led to the build-up of amino acids, coenzymes and phosphate-based small carbon molecules. Amino acids and similar building blocks could have been elaborated into proto-, with peptides being considered key players in the origin of life.
Reactions
Amino acids undergo the reactions expected of the constituent functional groups.
Peptide bond formation
As both the amine and carboxylic acid groups of amino acids can react to form amide bonds, one amino acid molecule can react with another and become joined through an amide linkage. This polymerization of amino acids is what creates proteins. This condensation reaction yields the newly formed peptide bond and a molecule of water. In cells, this reaction does not occur directly; instead, the amino acid is first activated by attachment to a transfer RNA molecule through an ester bond. This aminoacyl-tRNA is produced in an ATP-dependent reaction carried out by an aminoacyl tRNA synthetase. This aminoacyl-tRNA is then a substrate for the ribosome, which catalyzes the attack of the amino group of the elongating protein chain on the ester bond. As a result of this mechanism, all proteins made by ribosomes are synthesized starting at their N-terminus and moving toward their C-terminus.
Catabolism
[[File:Amino acid catabolism revised.png|thumb|300px|Catabolism of proteinogenic amino acids. Amino acids can be classified according to the properties of their main degradation products:
* 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.]]
Complexation
Amino acids are bidentate ligands, forming transition metal amino acid complexes.
Chemical analysis
The total nitrogen content of organic matter is mainly formed by the amino groups in proteins. The Total Kjeldahl Nitrogen (TKN) is a measure of nitrogen widely used in the analysis of (waste) water, soil, food, feed and organic matter in general. As the name suggests, the Kjeldahl method is applied. More sensitive methods are available.
See also
Notes
Further reading
External links
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