Abstract 2185 Clinical P1173L variant of methionine synthase impairs reductive methylation

Vitamin B12 (or cobalamin) is an essential nutrient that is obtained from the diet and used by only two enzymes in humans: cytoplasmic methionine synthase (MTR) and mitochondrial methylmalonyl CoA mutase. Cobalamin is loaded onto the target enzymes by chaperones, which were identified by clinical genetics studies on patients with cobalamin disorders. Clinical variants of MTR lead to homocystinuria, which is characterized by elevated homocysteine and associated with aggressive, occlusive cardiovascular diseases.