Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is the most common inborn error of sulfur amino acid metabolism. Which metabolite supplementation can reduce plasma homocysteine in the pyridoxine-responsive form?
- A Methionine supplementation to replenish the methyl-donor pool
- B Pyridoxal phosphate (vitamin B6) supplementation, as CBS requires PLP as a cofactor ✓
- C Vitamin B12 supplementation to regenerate methionine from homocysteine via methionine synthase
- D Cysteine supplementation to suppress CBS transcription
Explanation
CBS catalyzes the condensation of homocysteine with serine to form cystathionine, using pyridoxal phosphate (PLP) as a cofactor. In pyridoxine-responsive CBS deficiency (about 50% of cases), pharmacological doses of vitamin B6 stabilize the mutant enzyme, increasing residual activity and normalizing plasma homocysteine. Non-responsive cases are managed with methionine restriction and betaine (which acts as an alternative methyl donor for homocysteine remethylation to methionine). Vitamin B12 deficiency also elevates homocysteine but via impaired methionine synthase, a distinct mechanism.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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