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]
Authors
Sam Drabbe , Amaury Pelzer , Denise Slenter , Egon Willighagen , and Lars WillighagenActivity
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Organisms
Homo sapiensCommunities
Inherited Metabolic Disorders (IMD) Pathways Rare DiseasesAnnotations
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 pathwayDisease Ontology
beta-ketothiolase deficiencyCell Type Ontology
native cellLabel | 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] |
References
- 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
- 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