Pyridoxal phosphate-dependent decarboxylases and transaminases (PLP-DEs)

Pyridoxal phosphate-dependent decarboxylases and transaminases are a diverse group of enzymes that utilize pyridoxal 5'-phosphate (PLP), the active form of Vitamin B6, as an essential cofactor (NIH, 1.1.1). These enzymes are critical for the metabolism of amino acids and the biosynthesis of biogenic amines, including key neurotransmitters such as dopamine, serotonin, GABA, and histamine (ResearchGate, 1.1.2). In the catalytic process, PLP acts as an 'electron sink' to stabilize carbanionic intermediates, facilitating reactions like decarboxylation and transamination (Wikipedia, 1.2.1). Because of their central role in physiological processes, several members of this group are major therapeutic targets; for instance, DOPA decarboxylase is targeted in Parkinson's disease treatment, and GABA transaminase is targeted in epilepsy (PubMed, 1.3.1). Pharmacological intervention often involves suicide inhibitors that covalently modify the enzyme-cofactor complex, though the broad distribution of PLP-dependent enzymes can lead to off-target effects and systemic Vitamin B6 depletion (StatPearls). Clinical monitoring of these enzymes, particularly transaminases like ALT and AST, serves as a vital biomarker for organ health and drug-induced toxicity (NIH, 1.4.1). Therapeutic challenges include maintaining Vitamin B6 homeostasis and achieving selectivity among the numerous enzymes that share the PLP cofactor (ResearchGate, 1.4.2).

Other names

PLP-dependent enzymesVitamin B6-dependent enzymesB6-dependent enzymesPyridoxal 5'-phosphate-dependent enzymesPLP-dependent decarboxylasesPLP-dependent transaminasesAminotransferases

Drugs targeting these enzymes primarily act through suicide inhibition, where they form an irreversible covalent bond with the PLP cofactor or the active site lysine, or through competitive inhibition of the substrate binding site. Some drugs also act by depleting or sequestering the PLP cofactor itself.