Introduction

Vitamin B12 (cobalamin) is a scarce nutrient found mainly in foods of animal origin which is necessary for both hematopoiesis and myelination of the central and peripheral nervous system. It is widely recognized that seniors are at highest risk for vitamin B12 deficiency, and since vitamin B12 replacement is generally effective, inexpensive, and non-toxic, there is great incentive to find and correct deficiency. However, there are occasional difficulties diagnosing vitamin B12 deficiency, as will be outlined in this chapter.

Vitamin B12 is required for only two enzymes (see Table 14.1). As a cofactor for methionine synthase, methyl B12 participates in a reaction that converts homocysteine to methionine, producing the tetrahydrofolate needed for reactions of DNA and RNA synthesis. The other B12-dependent reaction salvages energy in the form of propionyl-CoA, which is converted to L-methylmalonyl-CoA. The adenosyl- B12-dependent enzyme L-methylmalonyl CoA mutase supplies succinyl-CoA to the Krebs cycle. The measurement of the substrates, homocysteine, and a product of methylmalonyl CoA, methylmalonic acid (MMA), have proved extremely useful in the diagnosis of vitamin B12 and folate deficiency. MMA and/or total homocysteine values are always (>95%) elevated in clinical B12 deficiency and are the first abnormality when B12 is withdrawn.