pyridoxal phosphate
Summary
Pyridoxal 5'-phosphate (PLP) is the active coenzyme form of vitamin B6, essential for amino acid metabolism including transamination, decarboxylation, and heme synthesis. It serves as a critical cofactor for enzymes like ALT, AST, and ALA synthase. Deficiency is classically associated with isoniazid use and presents with sideroblastic anemia, peripheral neuropathy, and seizures.
Detail
Pyridoxal phosphate (PLP) is derived from vitamin B6 (pyridoxine) through phosphorylation and oxidation. As a coenzyme, it forms Schiff base intermediates with amino acid substrates, enabling several key reactions: transamination (ALT/AST), decarboxylation (e.g., glutamate decarboxylase producing GABA, histidine decarboxylase producing histamine, and dopa decarboxylase), and the first step of heme synthesis via ALA synthase (combining glycine and succinyl-CoA to form delta-aminolevulinic acid). PLP is also required for cystathionine synthase in the transsulfuration pathway (homocysteine to cysteine) and for glycogen phosphorylase function in glycogenolysis.
Clinical relevance: Isoniazid (used for TB treatment) inhibits pyridoxine metabolism by forming a complex with PLP, leading to functional B6 deficiency. This can cause peripheral neuropathy (due to impaired myelin synthesis and neurotransmitter production) and sideroblastic anemia (due to impaired heme synthesis, causing iron accumulation in mitochondria of erythroblasts, seen as ringed sideroblasts). Prophylactic pyridoxine supplementation is given with isoniazid therapy to prevent these complications. B6 deficiency can also occur with certain oral contraceptives, alcoholism, and in patients on penicillamine. Severe deficiency can cause seizures, particularly in infants, due to decreased GABA synthesis. Excess vitamin B6 supplementation can paradoxically cause peripheral neuropathy.
PLP is measured indirectly via the tryptophan load test (xanthurenic acid excretion increases with B6 deficiency) since kynureninase requires PLP as a cofactor.
Sources
- First Aid for the USMLE Step 1
- Lippincott Biochemistry
- Harrison's Principles of Internal Medicine
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