Pyridoxal kinase (PDXK) (PDXK)

Pyridoxal kinase (PDXK) is a key enzyme in the salvage pathway of vitamin B6, catalyzing the ATP-dependent phosphorylation of pyridoxal, pyridoxine, and pyridoxamine into their active form, pyridoxal-5'-phosphate (PLP) [1, 3]. PLP serves as an indispensable cofactor for a vast array of enzymes, known as PLP-dependent enzymes, which are involved in amino acid metabolism, heme biosynthesis, and the production of neurotransmitters like gamma-aminobutyric acid (GABA), serotonin, and dopamine [2, 5]. Dysregulation or inhibition of PDXK leads to a systemic deficiency of PLP, which is linked to various pathologies including epilepsy, peripheral neuropathy, and sideroblastic anemia [2, 4]. Several drugs, most notably the antitubercular agent isoniazid, act as inhibitors of PDXK or chemically react with PLP, necessitating vitamin B6 supplementation to prevent neurotoxicity [4]. Furthermore, certain toxins like ginkgotoxin found in Ginkgo biloba seeds can inhibit PDXK, leading to "gin-nan" food poisoning characterized by seizures [5]. Understanding the interaction between PDXK and its downstream PLP-dependent enzymes is crucial for managing metabolic disorders and drug-induced side effects [1, 2]. This target is central to both nutritional biochemistry and clinical pharmacology due to its role in maintaining the functional pool of one of the body's most versatile cofactors [3].

Other names

PDX kinaseVitamin B6 kinasePdxKPyridoxine kinasePyridoxal-5'-phosphate-dependent enzymes

Inhibition of pyridoxal kinase prevents the phosphorylation of vitamin B6 precursors into the active cofactor pyridoxal-5'-phosphate (PLP), subsequently reducing the activity of numerous PLP-dependent enzymes [1, 4].