A patient with homocystinuria due to cystathionine beta-synthase (CBS) deficiency is also heterozygous for MTHFR C677T polymorphism. Treatment with pyridoxine (B6) is the first-line approach. The reason pyridoxine reduces homocysteine is:
- A Pyridoxine activates methionine synthase, rerouting homocysteine to methionine
- B Pyridoxine inhibits methionine adenosyltransferase, reducing SAM production
- C Pyridoxal phosphate (PLP) is a cofactor for CBS, and B6-responsive CBS mutants retain partial activity when flooded with PLP ✓
- D PLP is a cofactor for methylenetetrahydrofolate reductase (MTHFR)
Correct answer: C. Pyridoxal phosphate (PLP) is a cofactor for CBS, and B6-responsive CBS mutants retain partial activity when flooded with PLP
Explanation
CBS catalyses the condensation of homocysteine + serine → cystathionine, using PLP as cofactor. Many CBS mutations are B6-responsive: the mutant enzyme retains some residual catalytic activity that is dramatically increased when PLP concentrations are supranormal (pharmacological B6 supplementation). Approximately 50% of CBS-deficient patients respond to B6. Non-responders require betaine (methyl donor to remethylate homocysteine to methionine) and methionine restriction. Methionine synthase uses methylcobalamin (B12), not B6.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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