Vitamin B6 metabolism

Category: biosynthesis

Overview

Vitamin B6 has 6 vitamers; the active coenzyme is pyridoxal 5'-phosphate (PLP). Cofactor for ~150 enzymes — virtually all aminotransferases, decarboxylases (AADC → catecholamines + serotonin, GAD → GABA), heme synthesis (ALA synthase, see heme_biosynthesis), glycogen phosphorylase, cystathionine β-synthase (CBS, methionine cycle transsulfuration), kynureninase (tryptophan kynurenine path). Deficiency: peripheral neuropathy + sideroblastic anemia + seizures (especially in neonates with PNPO deficiency or ALDH7A1 pyridoxine-dependent epilepsy — IV pyridoxine bolus is the diagnostic test). ISONIAZID + cycloserine + hydralazine deplete PLP (isoniazid forms a hydrazone) — pyridoxine 25-50 mg/d co-prescribed with INH for TB to prevent neuropathy. High-dose pyridoxine (>200 mg/d chronic) causes a sensory neuronopathy via paradoxical mechanism.

Organ Systems

• nervous
• immune-hematologic

Pathway Steps

1. pyridoxine → pyridoxal-5-phosphate — via pyridoxal kinase (PDXK) + PNPO (pyridox(am)ine 5'-phosphate oxidase). Pyridoxal kinase and PNPO convert the B6 vitamers to pyridoxal-5′-phosphate (PLP) — cofactor for ~150 enzymes, especially transaminases, the decarboxylases of GABA/dopamine/serotonin/histamine synthesis, and δ-ALA synthase. PNPO deficiency causes PLP-responsive neonatal seizures; isoniazid depletes PLP.

Known Modulators

• p5p (cofactor) — pyridoxal-5-phosphate (active B6 form). P5P; active coenzyme form; preferred over pyridoxine in B6-deficient + transaminase reactions

References

• PMID 15189147