pyridoxine

Pyridoxine is converted in the body to its active form, pyridoxal 5'-phosphate (PLP), which acts as a coenzyme for over 100 enzymatic reactions, most notably transamination (ALT/AST), decarboxylation reactions (e.g., synthesis of neurotransmitters like GABA, serotonin, dopamine, histamine, and norepinephrine), and the first step of heme synthesis catalyzed by ALA synthase (delta-aminolevulinic acid synthase). It is also required for glycogenolysis (as a cofactor for glycogen phosphorylase) and for the synthesis of niacin from tryptophan.

Clinical significance: - Deficiency: Causes peripheral neuropathy (due to impaired neurotransmitter synthesis and myelin issues), sideroblastic anemia (impaired heme synthesis), seizures (especially in infants, due to decreased GABA synthesis), stomatitis, glossitis, and cheilosis. Common causes of deficiency include isoniazid (INH) and hydralazine use, since both drugs form complexes with pyridoxine/PLP and increase its excretion, as well as oral contraceptive use and alcoholism. - Isoniazid neuropathy: INH inhibits pyridoxine metabolism, leading to functional B6 deficiency; pyridoxine supplementation is routinely given with INH therapy to prevent peripheral neuropathy and is used as an antidote in acute INH overdose-induced seizures. - Sideroblastic anemia: Pyridoxine-responsive sideroblastic anemia occurs due to impaired ALA synthase function; supplementation can improve heme synthesis in certain cases (e.g., X-linked sideroblastic anemia from ALAS2 mutations). - Toxicity: Excess pyridoxine (usually from megadose supplementation) can cause a reversible sensory neuropathy.

Key associations for boards: INH-induced neuropathy prevention/treatment, sideroblastic anemia, cofactor for transamination and decarboxylation reactions, heme synthesis (ALA synthase), and neurotransmitter synthesis.