Amino acid
In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound from asparagus that they named asparagine. This marked the first time an amino acid was discovered in human history. The discovery of cystine followed in 1810, though its monomer form, cysteine, remained unknown until 1884. Glycine and leucine were identified in 1820, expanding the known list of these organic compounds. The final common amino acid to be found was threonine, which William Cumming Rose discovered in 1935. Rose also determined the essential amino acids and established minimum daily requirements for optimal growth. Wurtz recognized the unity of this chemical category in 1865 but did not give it a specific name at the time. The term "amino acid" first appeared in English language usage in 1898, while German speakers had used their own version earlier. Emil Fischer and Franz Hofmeister independently proposed in 1902 that proteins consist of many amino acids linked together. They described how bonds form between the amino group of one molecule and the carboxyl group of another.
The carbon atom next to the carboxyl group is called the alpha-carbon. In proteinogenic amino acids, this carbon bears the amine group, the side chain, and a hydrogen atom. With the exception of glycine, where the side chain is also a hydrogen atom, the alpha-carbon is stereogenic. All chiral proteogenic amino acids have the L configuration, meaning they are left-handed enantiomers. A few D-amino acids exist in nature, such as those found in bacterial envelopes or acting as neuromodulators like D-serine. Rarely, D-amino acid residues appear in proteins, converted from L-amino acids through post-translational modification. The common natural forms of amino acids possess a zwitterionic structure with both positive and negative charges on the same carbon atom. This zwitterion has a net charge of zero but contains separated charged sites. At physiological pH, the overall structure exists as a deprotonated carboxylate group and a protonated ammonio group. In low-dielectric hydrophobic environments, charge separation is poorly stabilized, yielding a neutral form instead. Spectroscopic studies show that most amino acids adopt neutral structures in the gas phase unless specific intramolecular interactions stabilize the zwitterion.
Five amino acids possess a charge at neutral pH, often appearing on protein surfaces to enable solubility in water. Aspartate and glutamate carry negative charges, while arginine, lysine, and histidine carry positive charges. These oppositely charged side chains form electrostatic contacts called salt bridges that maintain protein structures. Histidine's imidazole group has a pKa of 6.0 and is only around 10% protonated at neutral pH. Because it easily switches between basic and conjugate acid forms, histidine participates in catalytic proton transfers during enzyme reactions. Polar uncharged amino acids like serine, threonine, asparagine, and glutamine readily form hydrogen bonds with water. Tyrosine features a phenolic hydroxyl group with a pKa near 10, giving it amphipathic character despite being classified as neutral polar. Nonpolar amino acid interactions drive the folding of proteins into functional three-dimensional structures. Hydrophobic residues such as leucine, isoleucine, valine, phenylalanine, and tryptophan bury themselves inside proteins. Glycine offers unique flexibility due to its small size and lack of a side chain. Cysteine can form covalent disulfide bonds with other cysteines, influencing protein stability and antibody formation. Proline joins back onto the alpha amino group, creating an alkyl cycle that makes it particularly inflexible.
Amino acids join by condensation reactions to form short polymer chains called peptides or longer chains known as polypeptides or proteins. These linear, unbranched chains attach each residue to two neighboring amino acids through peptide bonds. The process of making proteins encoded by RNA genetic material is called translation and involves step-by-step addition by a ribosome. The order in which amino acids are added reads from an mRNA template derived from one of the organism's genes. There are 22 amino acids naturally incorporated into polypeptides, with 20 encoded by the universal genetic code. Selenocysteine and pyrrolysine are incorporated via unique synthetic mechanisms using variant codons. Selenocysteine appears when the mRNA includes a SECIS element causing the UGA codon to encode selenocysteine instead of stopping translation. Pyrrolysine is used by some methanogenic archaea in enzymes producing methane, coded for with the UAG codon. Twenty-five human proteins include selenocysteine in their primary structure, employing it as the catalytic moiety in active sites. N-formylmethionine often serves as the initial amino acid of proteins in bacteria, mitochondria, and chloroplasts. Hydroxyproline generated by hydroxylation of proline forms a major component of connective tissue collagen. Hypusine contains a modification of lysine found within the translation initiation factor EIF5A.
Animals ingest amino acids in the form of protein, which breaks down into constituent amino acids during digestion. The oxidation pathway starts with removal of the amino group by a transaminase, feeding the amino group into the urea cycle. Glucogenic amino acids can convert into glucose through gluconeogenesis, while ketogenic products may enter lipid synthesis or ketogenesis. Nine standard amino acids called essential cannot be synthesized by the human body at levels needed for normal growth. These nine are histidine, isoleucine, leucine, lysine, methinine, phenylalanine, threonine, tryptophane, and valine. Cysteine, tyrosine, and arginine are considered semiessential amino acids, while taurine is a semi-essential aminosulfonic acid in children. Some amino acids become conditionally essential depending on age or medical conditions. In many vertebrates, the amino group releases as ammonia and converts to urea via the urea cycle for excretion. Serine dehydratase converts serine directly to pyruvate and ammonia without requiring the full urea cycle. After removing one or more amino groups, the remaining carbon skeleton serves as a precursor for synthesizing other amino acids. This carbon skeleton can also metabolize for energy after conversion into glycolysis intermediates or citric acid cycle components.
The formation of amino acids and peptides likely preceded and perhaps induced the emergence of life on Earth. Surface-based chemical metabolism of amino acids and very small compounds may have led to build-up of coenzymes and phosphate-based molecules. The famous Urey-Miller experiment passed an electric arc through methane, hydrogen, and ammonia to produce numerous amino acids. Scientists discovered various ways prebiotic formation and chemical evolution of peptides could occur, including condensing agents and self-replicating peptide designs. Several hypotheses invoke the Strecker synthesis where hydrogen cyanide, simple aldehydes, ammonia, and water produce amino acids. Amino acids turn up fairly regularly in experimental broths cooked from simple chemicals because nucleotides are far harder to synthesize chemically. Chronological order suggests there must have been a protein world or polypeptide world possibly followed by RNA and DNA worlds. Codon-amino acid mappings may represent the biological information system at the primordial origin of life on Earth. While amino acids formed under different geochemical scenarios, the transition from abiotic world to first life forms remains largely unresolved.
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 like 2-Aminothiazoline-4-carboxylic acid used for L-cysteine synthesis. Aspartic acid is produced by adding ammonia to fumarate using a lyase enzyme. The food industry consumes glutamic acid as a flavor enhancer and aspartame as an artificial sweetener. Amino acids sometimes alleviate symptoms of mineral deficiencies by improving absorption and reducing negative side effects from inorganic supplementation. Animal feed often includes lysine, methionine, threonine, and tryptophan to correct low levels found in components like soybeans. Chelating ability allows amino acids to facilitate delivery of minerals to plants in fertilizers correcting iron chlorosis. Polyaspartate serves as a water-soluble biodegradable polymer with applications in disposable diapers and agriculture. This material also functions as a biodegradable antiscaling agent and corrosion inhibitor due to its solubility and metal chelation properties. Solid-phase peptide synthesis uses aromatic oxime derivatives of amino acids as activated units added sequentially onto growing chains attached to solid resin supports.
Common questions
When was the first amino acid discovered and by whom?
The first amino acid, asparagine, was isolated in 1806 by French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet. This discovery marked the first time an amino acid was found in human history.
What is the significance of the alpha-carbon in proteinogenic amino acids?
The carbon atom next to the carboxyl group is called the alpha-carbon and bears the amine group, side chain, and hydrogen atom in proteinogenic amino acids. With the exception of glycine, this alpha-carbon is stereogenic and all chiral proteogenic amino acids have the L configuration.
Which nine standard amino acids are essential for human growth?
Nine standard amino acids called essential cannot be synthesized by the human body at levels needed for normal growth. These nine are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine.
How many amino acids are naturally incorporated into polypeptides according to the universal genetic code?
There are 22 amino acids naturally incorporated into polypeptides with 20 encoded by the universal genetic code. Selenocysteine and pyrrolysine are incorporated via unique synthetic mechanisms using variant codons.
When did the term amino acid first appear in English language usage?
The term amino acid first appeared in English language usage in 1898 while German speakers had used their own version earlier. Emil Fischer and Franz Hofmeister independently proposed in 1902 that proteins consist of many amino acids linked together.