Gene-nutrient interactions in homocysteine metabolism: Regulation of human methionine synthase by B12

TL;DRAbstract

Studies spanning the last decade have linked elevated plasma homocysteine with increased risk for cardiovascular and other diseases. Homocysteine is a sulfur containing amino acid and its metabolism is directly controlled by the activity of three enzymes: B6 dependent cystathionine beta-synthase, B12-dependent methionine synthase (MS), and betaine homocysteine methyl transferase. Homocysteine can either condense with serine in a reaction catalyzed by cystathionine beta-synthase or be methylated to methionine in a reaction catalyzed by betaine homocysteine methyl transferase (with limited tissue distribution) or by MS. Several studies indicate the benefit of multivitamin (B6, B12 and folate) treatment in lowering plasma homocysteine. Mutations in MS are correlated with hereditary hyperhomocysteinemia. It was first reported over 30 years ago that the activity of MS in cultured cells was enhanced several fold upon supplementation with vitamin B12 . However, the mechanism of this activatio

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