Vitamin B-12.

V itamin B-12 is a cofactor for 2 enzymes. In the cytoplasm, methionine synthase requires vitamin B-12 in the form of methylcobalamin and catalyzes the conversion of homocysteine to methi-onine by transfer of a methyl group from methyltet-rahydrofolate. This enzyme links the methylation pathway through synthesis of the methyl donor S-adenosyl methionine and the pathway in which purine and pyrimidine are synthesized via generation of tetrahydrofolate. In the form of 59-deoxyadenosyl-cobalamin, vitamin B-12 is also required for the mi-tochondrial enzyme methylmalonyl CoA mutase, which converts methylmalonyl CoA to succinyl CoA, a step in the oxidation of odd-chain fatty acids and catabolism of ketogenic amino acids. Thus, vitamin B-12 is important for DNA synthesis, regenerating me-thionine for protein synthesis and methylation, and preventing homocysteine accumulation (1). Deficiencies: Serum (or plasma) vitamin B-12 concentration is the most frequently used biomarker of status with values ,150 pmol/L (,200 pg/mL) indicating deficiency, and 150–221 pmol/L (200–300 pg/mL) indicating depletion. Holotranscobalamin may be a more sensitive indicator of depletion than serum vitamin B-12 in some conditions (e.g., after intestinal radiation therapy for cancer and in HIV/AIDS), but the usual cutoff of 30 pmol/L (40 pg/mL) often estimates a similar population prevalence of deficiency as serum vitamin B-12. Holotranscobalamin is the metabolically active transport form of the vitamin, so there is interest in whether it is more sensitive for detecting the adverse effects of deficiency on function. Elevated serum or urinary methylmalonic acid is the most specific indicator of vitamin B-12 deficiency, but its analysis is usually expensive and more difficult than serum vitamin B-12, and serum creatinine must be measured to confirm normal renal function. Plasma total homocys-teine is a relatively sensitive indicator of vitamin B-12 deficiency, but it is not specific; it is also increased in folate, riboflavin, and vitamin B-6 deficiencies and in conditions such as hypothyroidism and kidney disease. Relatively severe vitamin B-12 deficiency impairs red blood cell synthesis (megaloblastic anemia due to abnormal DNA synthesis) and neurological function (demyelination of nerves in part due to abnormal methylation, leading to peripheral neuropathy, dementia, poor cognitive performance, and depression). Some neurological effects can be permanent, especially after 1 y. Deficiency or depletion is also associated with increased risk of neural tube defects, bone loss, and inflammation. Breast-fed infants born to mothers who are strictly vegetarian are at risk of permanent developmental delays because they have low vitamin B-12 stores at birth followed by …