Vitamin B12 disorders (WP4271)

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)).
last edited

Authors

Mzolisi, Khanspers, DeSl, Egonw, IreneHemel, Eweitz, Finterly, and Fehrhart

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

Cell Type Ontology: eukaryotic cell obsolete metabolising cell

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

Participants

Label Type Compact Identifier
Methylmalonic Acid Metabolite wikidata:Q239598
Hcy Metabolite wikidata:Q192466
cbLF Protein eccode:2.1.1.133
NADP+ Metabolite chebi:18009
FAD Metabolite chebi:16238
Adenosylcobalamin Metabolite wikidata:Q47517602
2 * SAH Metabolite chebi:16680
FMN Metabolite chebi:17621
MMA Metabolite wikidata:Q239598
NADPH Metabolite chebi:16474
2 * SAM Metabolite chebi:15414
Succinyl-CoA Metabolite chebi:15380
MUT Protein uniprot:P22033
cbLD-II Protein uniprot:Q9H3L0
Methionine Metabolite chebi:16811
MTHF Metabolite chebi:25345
TC receptor Protein uniprot:Q9NPF0
TC II Protein uniprot:P20062
HC Protein uniprot:P20061
CUBN Protein uniprot:O60494
Cbl Metabolite wikidata:Q3329800
Cbl Metabolite wikidata:Q3329800
HC Protein uniprot:P20061
Cbl Metabolite wikidata:Q3329800
HC Protein uniprot:P20061
Cbl Metabolite wikidata:Q3329800
IF Protein uniprot:P27352
IF Protein uniprot:P27352
Cbl Metabolite wikidata:Q3329800
IF Protein uniprot:P27352
AMN Protein uniprot:Q9BXJ7
Cbl Metabolite wikidata:Q3329800
IF Protein uniprot:P27352
TC II Protein uniprot:P20062
HC Protein uniprot:P20061
IF Protein uniprot:P27352
Cbl Metabolite wikidata:Q3329800
HC Protein uniprot:P20061
Cbl Metabolite wikidata:Q3329800
HC Protein uniprot:P20061
Cbl Metabolite wikidata:Q3329800
TC II Protein uniprot:P20062
Cbl Metabolite wikidata:Q3329800
TC II Protein uniprot:P20062
TC receptor Protein uniprot:Q9NPF0
Cbl Metabolite wikidata:Q3329800
TC II Protein uniprot:P20062
Cbl(cyanocobalamin) Metabolite wikidata:Q27286306
Cbl(cob(II)alamin) Metabolite chebi:16304
cbLJ Protein eccode:2.1.1.131
cbLC Protein uniprot:Q9Y4U1
2 * Cbl(cob(III)alamine) Metabolite chebi:28911
Cbl(cob(III)alamine) Metabolite chebi:28911
Cbl Metabolite wikidata:Q3329800
cbLB Protein uniprot:Q96EY8
cbLA Protein uniprot:Q8IVH4
Methylmalonyl-CoA Metabolite chebi:16625
cbLD-I Protein uniprot:Q9H3L0
cbLD Protein uniprot:Q9H3L0
Methylcobalamin Metabolite chebi:28115
cbLE Protein uniprot:Q9UBK8
Homocysteine Metabolite wikidata:Q192466
THF Metabolite chebi:67016
cbLG Protein uniprot:Q99707
coBM/cbLF Protein eccode:2.1.1.133
cbLC Protein uniprot:Q9Y4U1
cbLC Protein uniprot:Q9Y4U1
cbLC Protein uniprot:Q9Y4U1
FAD Metabolite chebi:16238
FMN Metabolite chebi:17621
NADPH Metabolite chebi:16474
Cofactor Metabolite chebi:28115
Protein in Complex Protein ensembl:ENSG00000116984

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. PubMed Europe PMC Scholia