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

Pyridoxal 5'-phosphate (PLP)-dependent enzymes constitute a vast and diverse superfamily of catalysts that utilize the active form of Vitamin B6 to facilitate over 140 distinct biochemical reactions, primarily centered on amino acid metabolism (PMID: 30103319). These enzymes are essential for the biosynthesis of critical signaling molecules, including neurotransmitters like gamma-aminobutyric acid (GABA), dopamine, and serotonin, as well as the production of heme and sphingolipids (PMID: 21534749). Due to their fundamental roles in physiology, specific members of this family serve as key therapeutic targets for conditions such as epilepsy, Parkinson's disease, and bacterial infections (StatPearls). For example, vigabatrin acts as a suicide inhibitor of GABA aminotransferase, while carbidopa inhibits peripheral DOPA decarboxylase to enhance levodopa efficacy (FDA). A significant challenge in targeting these enzymes is their shared reliance on the PLP cofactor and similar active site architectures, which can lead to off-target inhibition and systemic Vitamin B6 deficiency (PMID: 17570344). Consequently, drugs that interfere with PLP chemistry, such as the antitubercular agent isoniazid, often require co-administration of pyridoxine to mitigate side effects like peripheral neuropathy (Mayo Clinic).

Other names

Vitamin B6-dependent enzymePLP-dependent enzymePyridoxal phosphate-dependent enzyme

Suicide inhibition of specific PLP-dependent enzymes; competitive inhibition of the PLP binding site; chemical sequestration of the PLP cofactor.