Biotin metabolism, including IMDs (WP5031)
Homo sapiens
An important cofactor for carboxylation reaction is the vitamin Biotin. Four carboxylase groups (ACC, MCC, PCC and PC) are activated by binding to biotin and forming holocarboxylases, which in turn are responsible for several metabolic conversion in the Fatty Acid Synthesis, Leucine catabolism, propanoate metabolism and gluconeogenesis. Except for the ACC conversion from acetyl-CoA to malonyl-CoA starting the fatty acid synthesis, all other three interactions are connected to disorders. Furthermore, one can distinguish two "multiple carboxylase defects" (MCDs), which are connected to the conversion of biocytin into biotin (BTD), or unbound biotin to one of the apocarboxylases (HCSD). This pathway was inspired by Chapter 14 (edition 4) of the book of Blau (ISBN 3642403360 (978-3642403361)).
Authors
Denise Slenter , Egon Willighagen , Eric Weitz , and Finterly HuActivity
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Organisms
Homo sapiensCommunities
Inherited Metabolic Disorders (IMD) Pathways Rare DiseasesAnnotations
Disease Ontology
3-Methylcrotonyl-CoA carboxylase 2 deficiency pyruvate carboxylase deficiency disease 3-Methylcrotonyl-CoA carboxylase 1 deficiency 3-Methylcrotonyl-CoA carboxylase deficiency holocarboxylase synthetase deficiency biotinidase deficiencyPathway Ontology
3-methylcrotonyl CoA carboxylase 2 deficiency pathway 3-methylcrotonyl CoA carboxylase 1 deficiency pathway biotin metabolic pathway holocarboxylase synthetase deficiency pathway biotinidase deficiency pathway pyruvate carboxylase deficiency pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| pyruvate | Metabolite | chebi:15361 | |
| Apo-ACC | Metabolite | chebi:29969 | aka apo-[methylmalonyl-CoA:pyruvate carboxytransferase] |
| propanoyl-CoA | Metabolite | chebi:57392 | aka propionyl-CoA |
| leucine | Metabolite | chebi:25017 | |
| oxaloacetate | Metabolite | chebi:16452 | |
| 3-methylglutaconyl-CoA | Metabolite | chebi:57346 | aka trans-3-methylglutaconyl-CoA |
| 3-methylcrotonyl-COA | Metabolite | chebi:57344 | aka 3-methylbut-2-enoyl-CoA |
| Dietary and otherprotein-bound biotin | Metabolite | chebi:16615 | |
| Biocytin | Metabolite | wikidata:Q864247 | biotin covalantly bound to lysine |
| Lysine | Metabolite | chebi:25094 | |
| free biotin | Metabolite | chebi:15956 | |
| Acetyl-CoA | Metabolite | chebi:57288 | |
| Biotin (free pool) | Metabolite | chebi:15956 | |
| Malonyl-CoA | Metabolite | chebi:57384 | |
| holo-ACC | Metabolite | chebi:83144 | aka holo-[methylmalonyl-CoA:pyruvate carboxytransferase] |
| Apo-PCC | Metabolite | chebi:29969 | aka apo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)] |
| holo-PCC | Metabolite | chebi:83144 | aka holo-[propionyl-CoA:carbon-dioxide ligase (ADP-forming)] |
| Apo-MCC | Metabolite | chebi:29969 | aka apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] |
| holo-MCC | Metabolite | chebi:83144 | aka holo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)] |
| Apo-PC | Metabolite | chebi:29969 | aka pyruvate carboxylase |
| holo-PC | Metabolite | chebi:83144 | aka pyruvate carboxylase |
| Biotin | Metabolite | chebi:15956 | |
| methylmanoyl-CoA | Metabolite | chebi:57327 | |
| PC | Protein | uniprot:P11498 | aka pyruvate carboxylase |
| MCCC1 | Protein | uniprot:Q96RQ3 | |
| Biotinidase (BTD) | Protein | uniprot:P43251 | |
| HLCS | Protein | uniprot:P50747 | aka Holocarboxylase Synthetase |
| ACC1(cytosol) | Protein | uniprot:Q13085 | aka acetyl-CoA carboxylase |
| ACC2(mitochondrial) | Protein | uniprot:O00763 | aka acetyl-CoA carboxylase |
| MCCC2 | Protein | uniprot:Q9HCC0 | |
| PCCA | Protein | uniprot:P05165 | |
| PCCB | Protein | uniprot:P05166 |
References
- Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Blau N, Duran M, Gibson KM, Dionisi-Vici C. Springer; 2014. 0 p. Available from: https://books.google.com/books/about/Physician_s_Guide_to_the_Diagnosis_Treat.html?hl=&id=wJRBnwEACAAJ OpenLibrary Worldcat
- Biotinidase and its roles in biotin metabolism. Hymes J, Wolf B. Clin Chim Acta. 1996 Nov 15;255(1):1–11. PubMed Europe PMC Scholia
- Biotin: biochemical, physiological and clinical aspects. Said HM. Subcell Biochem. 2012;56:1–19. PubMed Europe PMC Scholia