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Vitamin B12: Disorders of Absorption and Metabolism

  1. David Watkins,
  2. David S Rosenblatt

Published Online: 15 FEB 2010

DOI: 10.1002/9780470015902.a0002267.pub2

eLS

eLS

How to Cite

Watkins, D. and Rosenblatt, D. S. 2010. Vitamin B12: Disorders of Absorption and Metabolism. eLS. .

Author Information

  1. McGill University, Department of Human Genetics, Montreal, Québec, Canada

Publication History

  1. Published Online: 15 FEB 2010

Abstract

Derivatives of vitamin B12 (cobalamin) are required for activity of two enzymes: methylmalonylCoA mutase, which catalyses conversion of methylmalonylCoA to succinylCoA and methionine synthase, which converts homocysteine to methionine. Cobalamin deficiency results in accumulation of methylmalonic acid and homocysteine in blood and urine. Clinically, deficiency results in megaloblastic anaemia, subacute combined degeneration of the spinal cord, loss of sensation, ataxia, dementia and psychosis. Dietary cobalamin deficiency is rare in developed countries, except for individuals consuming a vegan diet. A more common cause of cobalamin deficiency is pernicious anaemia, an autoimmune disease that results in inability to absorb dietary cobalamin from the intestine. A number of rare genetic disorders have been identified that result in inability to absorb dietary cobalamin, inability to transport cobalamin from the intestine to cells that require it for metabolism, or inability to convert intracellular cobalamin to one or both of its coenzyme derivatives, adenosylcobalamin and methylcobalamin.

Key Concepts:

  • Cobalamin (vitamin B12) is required for activity of two enzymes, methylmalonylCoA mutase and methionine synthase, in mammalian cells.

  • Cobalamin deficiency results in accumulation of methylmalonic acid and homocysteine in blood and urine.

  • Clinically, deficiency is characterized by megaloblastic anaemia and neurological problems.

  • Uptake of dietary cobalamin requires the binding protein intrinsic factor, secreted by parietal cells of the stomach, and the intestinal receptor cubam.

  • Autoimmune destruction of gastric parietal cells results in pernicious anaemia.

  • Mutations in the genes encoding intrinsic factor or components of cubam result in heritable cobalamin malabsorption.

  • Peripheral cells take up cobalamin bound to the transport protein transcobalamin by carrier-mediated endocytosis.

  • Cells convert cobalamin to adenosylcobalamin, required by methylmalonylCoA mutase, and methylcobalamin, required by methionine synthase.

  • Rare mutations affecting genes involved in cobalamin metabolism, result in decreased synthesis of either or both cobalamin derivatives.

Keywords:

  • vitamin B12;
  • cobalamin;
  • homocysteine;
  • methylmalonic acid;
  • anaemia