This pathway depicts the metabolism of cobalamin (also known as cbl or Vit. B12) and related diseases (for a full overview of the B12 metabolism, see [https://www.wikipathways.org/index.php/Pathway:WP1533]). Vit. B12 is derived from food sources and thereafter metabolised for 2 reasons; 1. to methylate homocysteine to methionine, and 2. to convert methylmalonyl-CoA to succinyl-CoA. This pathway depicts 15 distinct diseases which are related to a malfunctioning in the absorption and transport section, or the intracellular processing of Cbl. However, the exact function of some proteins which have been linked to these diseases, remains unclear. Substitution of Vit. B12 is a therapeutic option for patients with absorption and transport related diseases, however does not perform so well for patient with intracellular processing defects. This pathway was inspired by Chapter 13 of the book of Blau (ISBN 3642403360 (978-3642403361)).

Authors

Mzolisi Mtshaulana , Kristina Hanspers , Denise Slenter , Egon Willighagen , Irene Hemel , Eric Weitz , Finterly Hu , and Friederike Ehrhart

Cited In

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Organism

Homo sapiens

Communities

Inborn Errors of Metabolism (IEM) Pathways Rare Diseases

Annotations

Disease Ontology: methylmalonic aciduria and homocystinuria type cblD methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency vitamin B12 deficiency methylmalonic acidemia cblA type methylmalonic acidemia cblB type methylmalonic acidemia methylmalonic aciduria and homocystinuria type cblC methylmalonic aciduria and homocystinuria type cblF

Pathway Ontology: mitochondria dynamics pathway methylmalonic aciduria, cobalamin-related pathway cobalamin metabolic pathway

Cell Type Ontology: obsolete metabolising cell eukaryotic cell

Participants

References

1. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Springer; 2014. 867 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
2. Raux E, Schubert HL, Warren MJ. Biosynthesis of cobalamin (vitamin B12): a bacterial conundrum. Cell Mol Life Sci. 2000 Dec;57(13–14):1880–93. PubMed Europe PMC Scholia
3. Wolthers KR, Lou X, Toogood HS, Leys D, Scrutton NS. Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry. Biochemistry. 2007 Oct 23;46(42):11833–44. PubMed Europe PMC Scholia
4. Froese DS, Zhang J, Healy S, Gravel RA. Mechanism of vitamin B12-responsiveness in cblC methylmalonic aciduria with homocystinuria. Mol Genet Metab. 2009 Dec;98(4):338–43. PubMed Europe PMC Scholia
5. Froese DS, Gravel RA. Genetic disorders of vitamin B₁₂ metabolism: eight complementation groups--eight genes. Expert Rev Mol Med. 2010 Nov 29;12:e37. PubMed Europe PMC Scholia
6. Watkins D, Rosenblatt DS. Inborn errors of cobalamin absorption and metabolism. Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):33–44. PubMed Europe PMC Scholia
7. Yamada K, Gherasim C, Banerjee R, Koutmos M. Structure of Human B12 Trafficking Protein CblD Reveals Molecular Mimicry and Identifies a New Subfamily of Nitro-FMN Reductases. J Biol Chem. 2015 Dec 4;290(49):29155–66. PubMed Europe PMC Scholia