Pyridoxal 5'-phosphate-dependent enzyme (PLP-dependent enzyme) (PLP-DE)

Pyridoxal 5'-phosphate-dependent enzymes (PLP-dependent enzymes) represent a large and functionally diverse family of enzymes that utilize the active form of Vitamin B6, pyridoxal 5'-phosphate, as an essential cofactor. These enzymes catalyze over 140 distinct biochemical reactions, primarily involving the metabolism of amino acids, including transamination, decarboxylation, racemization, and elimination. They play critical roles in the synthesis of key neurotransmitters such as gamma-aminobutyric acid (GABA), dopamine, and serotonin, as well as in heme biosynthesis and sphingolipid metabolism. Due to their central role in metabolism, several PLP-dependent enzymes are major therapeutic targets; for example, GABA aminotransferase is targeted by vigabatrin for epilepsy, and DOPA decarboxylase is inhibited by carbidopa to manage Parkinson's disease. However, the high reactivity of the PLP cofactor and the structural conservation across the family can lead to off-target interactions, resulting in safety concerns such as peripheral neuropathy and Vitamin B6 depletion.

Other names

Other PLP-dependent enzymesVitamin B6-dependent enzymesB6-dependent enzymesPLP-dependent enzymesPyridoxal phosphate-dependent enzymes

Drugs typically act as suicide inhibitors by forming covalent bonds with the PLP cofactor (mechanism-based inhibition) or as competitive inhibitors that block the active site or interfere with the formation of the internal aldimine.