Pyridoxal kinase and pyridoxal-phosphate-dependent enzymes (PDXK and PLP-dependent enzymes)

Pyridoxal kinase (PDXK) is a key enzyme in the vitamin B6 salvage pathway, responsible for phosphorylating pyridoxal, pyridoxine, and pyridoxamine into their active coenzyme form, pyridoxal 5'-phosphate (PLP) (UniProt: P12591). PLP serves as an essential cofactor for a vast array of enzymes, collectively known as PLP-dependent enzymes, which catalyze critical reactions in amino acid metabolism, heme biosynthesis, and the production of neurotransmitters such as GABA, serotonin, and dopamine (PubMed: 21834930). Because of this central role, the activity of PDXK and its downstream enzymes is vital for maintaining neurological function and metabolic homeostasis (StatPearls: Vitamin B6 Deficiency). Many pharmacological agents, most notably the anti-tuberculosis drug isoniazid, can interfere with this system by inhibiting PDXK or sequestering PLP, leading to clinical vitamin B6 deficiency (PubMed: 11696052). Such interference often manifests as peripheral neuropathy or seizures, necessitating co-administration of vitamin B6 in certain therapeutic contexts (NIH: Vitamin B6 Fact Sheet). Conversely, specific PLP-dependent enzymes are targeted directly for the treatment of diseases like Parkinson's or epilepsy (PubMed: 25613473).

Other names

Vitamin B6 kinase (UniProt: P12591)PLP-dependent enzymes (PubMed: 21834930)Pyridoxal 5'-phosphate-dependent enzymes (PubMed: 21834930)B6-dependent enzymes (StatPearls: Vitamin B6 Deficiency)

Inhibition of pyridoxal kinase prevents the formation of the active cofactor pyridoxal 5'-phosphate (PLP); drugs may also directly inhibit PLP-dependent enzymes or sequester PLP through adduct formation (PubMed: 11696052, 21834930).