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)).


Denise Slenter , Egon Willighagen , Eric Weitz , and Finterly Hu


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


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 deficiency

Pathway 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


  1. 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: OpenLibrary Worldcat
  2. 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
  3. Biotin: biochemical, physiological and clinical aspects. Said HM. Subcell Biochem. 2012;56:1–19. PubMed Europe PMC Scholia