Biotin metabolism, including IEMs (WP5031)

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)).
last edited


DeSl, Egonw, Eweitz, and Finterly

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Homo sapiens


Inborn Errors of Metabolism (IEM) 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 Identifier
pyruvate Metabolite chebi:15361
Apo-ACC Metabolite chebi:29969
propanoyl-CoA Metabolite chebi:57392
leucine Metabolite chebi:25017
oxaloacetate Metabolite chebi:16452
PC Protein uniprot:P11498
3-methylglutaconyl-CoA Metabolite chebi:57346
Fatty Acid Synthesis Pathway wikipathways:WP3965
MCCC1 Protein uniprot:Q96RQ3
3-methylcrotonyl-COA Metabolite chebi:57344
Dietary and otherprotein-bound biotin Metabolite chebi:16615
Proteolysis Protein None
Biocytin Metabolite wikidata:Q864247
Lysine Metabolite chebi:25094
Biotinidase (BTD) Protein uniprot:P43251
free biotin Metabolite chebi:15956
Acetyl-CoA Metabolite chebi:57288
Biotin (free pool) Metabolite chebi:15956
HLCS Protein uniprot:P50747
Malonyl-CoA Metabolite chebi:57384
ACC1(cytosol) Protein uniprot:Q13085
ACC2(mitochondrial) Protein uniprot:O00763
LeucineCatabolism Pathway wikipathways:WP4686
Propanoatemetabolism Pathway wikipathways:WP4034
Gluconeogenesis,Anaplerosis Pathway wikipathways:WP534
holo-ACC Metabolite chebi:83144
Apo-PCC Metabolite chebi:29969
holo-PCC Metabolite chebi:83144
Apo-MCC Metabolite chebi:29969
holo-MCC Metabolite chebi:83144
Apo-PC Metabolite chebi:29969
holo-PC Metabolite chebi:83144
MCCC2 Protein uniprot:Q9HCC0
Biotin Metabolite chebi:15956
PCCA Protein uniprot:P05165
PCCB Protein uniprot:P05166
methylmanoyl-CoA Metabolite chebi:57327


  1. Hymes J, Wolf B. Biotinidase and its roles in biotin metabolism. Clin Chim Acta. 1996 Nov 15;255(1):1–11. PubMed Europe PMC Scholia
  2. Said HM. Biotin: biochemical, physiological and clinical aspects. Subcell Biochem. 2012;56:1–19. PubMed Europe PMC Scholia
  3. PubMed Europe PMC Scholia