13-06: Vitamin B₁₂ Deficiency

GENERAL CONSIDERATIONS

Vitamin B₁₂ belongs to the family of cobalamins and serves as a cofactor for two important reactions in humans (eFigure 13–7). As methylcobalamin, it is a cofactor for methionine synthetase in the conversion of homocysteine to methionine, and as adenosylcobalamin for the conversion of methylmalonyl-coenzyme A (CoA) to succinyl-CoA. These enzymatic steps are critical for annealing Okazaki fragments during DNA synthesis, particularly in erythroid progenitor cells. Vitamin B₁₂ comes from the diet and is present in all foods of animal origin. The daily absorption of vitamin B₁₂ is 5 mcg.

After being ingested, vitamin B₁₂ is bound to intrinsic factor, a protein secreted by gastric parietal cells in an acid environment. Other cobalamin-binding proteins (called R factors) compete with intrinsic factor for vitamin B₁₂. Vitamin B₁₂ bound to R factors cannot be absorbed. The vitamin B₁₂–intrinsic factor complex travels through the intestine and is absorbed in the terminal ileum by cells with specific receptors for the complex. It is then transported through plasma and stored in the liver. Three plasma transport proteins have been identified. Transcobalamins I and III (differing only in carbohydrate structure) are secreted by white blood cells. Although approximately 90% of plasma vitamin B₁₂ circulates bound to transcobalamins I and III, only transcobalamin II is capable of transporting vitamin B₁₂ into cells.

The liver contains 2–5 mg of stored vitamin B₁₂. Since daily utilization is 3–5 mcg, the body usually has sufficient stores of vitamin B₁₂ so that it takes more than 3 years for vitamin B₁₂ deficiency to occur if all intake or absorption immediately ceases.

Since vitamin B₁₂ is present in foods of animal origin, dietary vitamin B₁₂ deficiency is extremely rare but is seen in vegans—strict vegetarians who avoid all dairy products, meat, and fish (Table 13–6). Pernicious anemia is an autoimmune illness whereby autoantibodies destroy gastric parietal cells (that produce intrinsic factor) and cause atrophic gastritis or bind to and neutralize intrinsic factor, or both. Abdominal surgery may lead to vitamin B₁₂ deficiency in ...