Disorders in ketone body synthesis (WP5175)

Homo sapiens

Ketone bodies, acetoacetate and (beta)3-hydroxybutyric acid, are produced in times of hunger/starvation. The compounds are water-soluble (and also include the spontaneous breakdown product of acetoacetate, acetone). All ketone bodies are by-products when fatty acids are broken down for energy in the liver and kidneys, and used as energy source for the heart and brain. Ketogenesis can be impeded by inborn errors of metabolism such as Methylacetoacetyl-CoA thiolase deficiency, 3-hydroxy-3-methylglutaryl-CoA synthase deficiency and 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. In this pathway ketogenesis is visualised and linked to the different diseases. Ketogenesis can derive from leucine metabolism and fatty acid beta-oxidation and happens in the mitochondria. The enzymes ACAT1, HMGCS2, HMGCL and BDH1 play an important role during this proces. This pathway is based on chapter 23 of the book of Blau et al. (ISBN 3642403360 (978-3642403361)), Figures 23.1 and 23.2. For the ketolysis pathway see: [https://www.wikipathways.org/index.php/Pathway:WP5195 WP5195]


Sam Drabbe , Amaury Pelzer , Denise Slenter , Egon Willighagen , and Lars Willighagen


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


Pathway Ontology

3-hydroxy-3-methylglutaryl-CoA lyase deficiency pathway classic metabolic pathway ketone bodies metabolic pathway disease pathway fatty acid metabolic pathway citric acid cycle pathway

Disease Ontology

beta-ketothiolase deficiency

Cell Type Ontology

native cell


Label Type Compact Identifier Comment
Acetoacetyl-CoA Metabolite chebi:15345 [PMID:14769483]
Coenzym A Metabolite chebi:15346
3-hydroxybutyric acid Metabolite chebi:20067 aka 3HB [PMID:14769483]
Acetyl-CoA Metabolite chebi:57288 [PMID:14769483]
acetoacetate Metabolite chebi:13705 [PMID:14769483]
acetone Metabolite chebi:15347
Leucine Metabolite chebi:15603
CoASH Metabolite chebi:15346
fatty acids Metabolite chebi:35366
NAD+ Metabolite chebi:15846
3-hydroxy-3-methylglutaryl-coenzyme A Metabolite chebi:11814 [PMID:14769483]
H+ Metabolite chebi:15378
NADH Metabolite chebi:16908
Acetyl-CoA Metabolite chebi:57288
H+ Metabolite chebi:15378
Carbon Dioxide Metabolite chebi:16526
HMGCL Protein uniprot:H0Y2L7
ACAT1 Protein uniprot:P24752 In the book by Blau et al. referred to as MAT ; [PMID:14769483]
OXCT1 Protein uniprot:P55809 [PMID:14769483]
BDH1 Protein uniprot:Q02338 In the book by Blau et al. they use the abbriviation 3HBD; [PMID:14769483]
HMGCS2 Protein uniprot:P54868 [PMID:14769483]


  1. Blau N, Duran M, Gibson KM, Dionisi Vici C, editors. Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases [Internet]. Springer Berlin Heidelberg; 2014. Available from: http://dx.doi.org/10.1007/978-3-642-40337-8 DOI
  2. Saudubray JM. Inborn Metabolic Diseases: Diagnosis and Treatment [Internet]. Springer; 2011. 660 p. Available from: https://openlibrary.org/books/OL26743756M/Inborn_Metabolic_Diseases_Diagnosis_and_Treatment OpenLibrary Worldcat