Defects in cobalamin (B12) metabolism

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
Click the image above or here to open this pathway in the Pathway Browser
Cobalamin (Cbl, vitamin B12) is a nutrient essential for normal functioning of the brain and nervous system and for the formation of blood. Cbl-dependent methionine synthase (MTR) is required for conversion of 5-methyltetrahydrofolate (metTHF) to tetrahydrofolate (THF), in addition to its role in conversion of homocysteine to methionine. In Cbl deficiency, and in inborn errors of Cbl metabolism that affect function of methionine synthase, inability to regenerate THF from metTHF results in decreased function of folate-dependent reactions that are involved in 2 steps of purine biosynthesis and thymidylate synthesis. Cbl deficiency results in hyperhomocysteinemia (due to defects in the conversion of homocysteine to methionine which requires Cbl as a cofactor) and increased levels of methylmalonic acid (MMA). Methionine is used in myelin production, protein, neurotransmitter, fatty acid and phospholipid production and DNA methylation. Symptoms of Cbl deficiency are bone marrow promegaloblastosis (megaloblastic anemia) due to the inhibition of DNA synthesis (specifically purines and thymidine) and neurological symptoms. The defective genes involved in Cbl deficiencies are described below (Froese & Gravel 2010, Nielsen et al. 2012, Whitehead 2006, Watkins & Rosenblatt 2011, Fowler 1998).
Literature References
PubMed ID Title Journal Year
16846473 Acquired and inherited disorders of cobalamin and folate in children

Whitehead, VM

Br. J. Haematol. 2006
9587028 Genetic defects of folate and cobalamin metabolism

Fowler, B

Eur. J. Pediatr. 1998
22547309 Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway

Rasmussen, MR, Moestrup, SK, Andersen, CB, Nielsen, MJ, Nexø, E

Nat Rev Gastroenterol Hepatol 2012
21312325 Inborn errors of cobalamin absorption and metabolism

Rosenblatt, DS, Watkins, D

Am J Med Genet C Semin Med Genet 2011
21114891 Genetic disorders of vitamin B12 metabolism: eight complementation groups--eight genes

Froese, DS, Gravel, RA

Expert Rev Mol Med 2010
Name Identifier Synonyms
vitamin B12 deficiency DOID:0050731 cobalamin deficiency, hypocobalaminemia
Cite Us!