In addition to the 20 proteinogenic amino acids (see p. 60), there are also many more compounds of the same type in nature. These arise during metabolic reactions (A) or as a result of enzymatic modifications of amino acid residues in peptides or proteins (B). The "biogenic amines" (C) are synthesized from a-amino acids by decarboxylation.
Only a few important representatives of the non-proteinogenic amino acids are mentioned here. The basic amino acid ornithine is an analogue of lysine with a shortened side chain. Transfer of a carbamoyl residue to ornithine yields citrulline. Both of these amino acids are intermediates in the urea cycle (see p.182). Dopa (an acronym of 3,4-dihydroxy-phenylalanine) is synthesized by hydroxyla-tion of tyrosine. It is an intermediate in the biosynthesis of catecholamines (see p. 352) and of melanin. It is in clinical use in the treatment of Parkinson's disease. Selenocys-teine, a cysteine analogue, occurs as a component of a few proteins—e.g., in the enzyme glutathione peroxidase (see p. 284).
Subsequent alteration of amino acid residues in finished peptides and proteins is referred to as post-translational modification. These reactions usually only involve polar amino acid residues, and they serve various purposes.
The free a-amino group at the N-terminus is blocked in many proteins by an acetyl residue or a longer acyl residue (acylation). N-terminal glutamate can cyclize into a pyroglutamate residue, while the C-terminal carbox-ylate group can be present in an amidated form (see TSH, p. 380). The side chains of serine and asparagine residues are often linked to oligosaccharides (glycosylation, see p. 230). Phosphorylation of proteins mainly affects serine and tyrosine residues. These reactions have mainly regulatory functions (see p. 114). Aspartate and histidine residues of enzymes are sometimes phosphorylated, too. A special modification of glutamate residues, y-carbox-ylation, is found in coagulation factors. It is essential for blood coagulation (see p. 290).
The e-amino group of lysine residues is subject to a particularly large number of modifications. Its acetylation (or deacetylation) is an important mechanism for controlling genetic activity (see p. 244). Many coenzymes and cofactors are covalently linked to lysine residues. These include biotin (see p.108), lipoic acid (see p.106), and pyridoxal phosphate (see p.108), as well as retinal (see p. 358). Covalent modification with ubiquitin marks proteins for breakdown (see p.176). In collagen, lysine and proline residues are modified by hydroxylation to prepare for the formation of stable fibrils (see p. 70). Cysteine residues form disulfide bonds with one another (see p. 72). Cysteine prenylation serves to anchor proteins in membranes (see p. 214). Covalent bonding of a cysteine residue with heme occurs in cytochrome c. Flavins are sometimes covalently bound to cysteine or histidine residues of enzymes. Among the modifications of tyrosine residues, conversion into iodinated thyroxine (see p. 374) is particularly interesting.
Several amino acids are broken down by de-carboxylation. This reaction gives rise to what are known as biogenic amines, which have various functions. Some of them are components of biomolecules, such as ethanolamine in phospholipids (see p. 50). Cysteamine and T-alanine are components of coenzyme A (see p.12) and of pantetheine (see pp.108, 168). Other amines function as signaling substances. An important neurotransmitter derived from glutamate is y-aminobutyrate (GABA, see p. 356). The transmitter dopamine is also a precursor for the catecholamines epineph-rine and norepinephrine (see p.352). The bio-genic amine serotonin, a substance that has many effects, is synthesized from tryptophan via the intermediate 5-hydroxytryptophan.
Monamines are inactivated into aldehydes by amine oxidase (monoamine oxidase, "MAO") with deamination and simultaneous oxidation. MAO inhibitors therefore play an important role in pharmacological interventions in neurotransmitter metabolism.
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