Pyridoxal 5'-phosphate-dependent amino acid metabolizing enzymes (PLP-dependent enzymes)

Pyridoxal 5'-phosphate (PLP)-dependent amino acid metabolizing enzymes represent a vast and functionally diverse superfamily of enzymes that utilize the active form of Vitamin B6 as an essential cofactor. These enzymes catalyze a multitude of chemical transformations, including transamination, decarboxylation, racemization, and side-chain eliminations or replacements, primarily centered on amino acid substrates (Source: PubMed, PMID: 21827277). They play critical roles in fundamental biological processes such as the synthesis of neurotransmitters like GABA, serotonin, and dopamine, as well as heme biosynthesis and the regulation of homocysteine levels (Source: UniProt). Because of their central position in metabolic pathways, they are key therapeutic targets in various conditions; for example, GABA aminotransferase is targeted in epilepsy, and DOPA decarboxylase is inhibited in the treatment of Parkinson's disease (Source: NIH, StatPearls). Many drugs acting on these enzymes function as suicide inhibitors that form a stable covalent bond with the PLP cofactor or the enzyme-PLP complex (Source: PubChem). However, therapeutic intervention must be carefully monitored, as off-target inhibition or interference with PLP availability can lead to Vitamin B6 deficiency, manifesting as peripheral neuropathy or seizures (Source: Mayo Clinic).

Other names

Vitamin B6-dependent enzymesPLP-dependent enzymesPyridoxal phosphate-dependent enzymesB6-dependent amino acid enzymes

Irreversible suicide inhibition of the enzyme-cofactor complex, competitive inhibition at the substrate binding site, and depletion or sequestration of the pyridoxal 5'-phosphate cofactor.