RGD Reference Report - Acetate generation in rat liver mitochondria; acetyl-CoA hydrolase activity is demonstrated by 3-ketoacyl-CoA thiolase. - Rat Genome Database

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Acetate generation in rat liver mitochondria; acetyl-CoA hydrolase activity is demonstrated by 3-ketoacyl-CoA thiolase.

Authors: Yamashita, H  Itsuki, A  Kimoto, M  Hiemori, M  Tsuji, H 
Citation: Yamashita H, etal., Biochim Biophys Acta. 2006 Jan;1761(1):17-23. Epub 2006 Jan 30.
RGD ID: 2317620
Pubmed: PMID:16476568   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbalip.2006.01.001   (Journal Full-text)

Acetate has been found as an endogenous metabolite of beta-oxidation of fatty acids in liver. In order to investigate the regulation of acetate generation in liver mitochondria, we attempted to purify a mitochondrial acetyl-CoA hydrolase in rat liver. This acetyl-CoA-hydrolyzing activity in isolated mitochondria was induced by the treatment of rats with di(2-ehtylhexyl)phthalate (DEHP), a peroxisome proliferator which induces expression of several peroxisomal and mitochondrial enzymes involved in beta-oxidation of fatty acids. The purified enzyme was 43-kDa in molecular mass by SDS/PAGE. Internal amino acid sequencing of this enzyme revealed that it was identical with mitochondrial 3-ketoacyl-CoA thiolase, suggesting that this enzyme has two kinds of activities, 3-ketoacyl-CoA thiolase and acetyl-CoA hydrolase activities. Kinetic studies clearly indicated that this enzyme had the both activities and each activity was inhibited by the substrates of the other activity, that is, 3-ketoacyl-CoA thiolase activity was inhibited by acetyl-CoA, on the other hand, acetyl-CoA hydrolase activity was inhibited by acetoacetyl-CoA in a competitive manner. These findings suggested that acetate generation in liver mitochondria is a side reaction of this known enzyme, 3-ketoacyl-CoA thiolase, and this enzyme may regulate its activities depending on each substrate level.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acetyl-CoA metabolic process  IDA 2317620 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mitochondrial matrix  IDA 2317620 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
acetyl-CoA C-acyltransferase activity  IDA 2317620 RGD 
fatty acyl-CoA hydrolase activity enablesIDA 2317620PMID:16476568UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Acaa2  (acetyl-CoA acyltransferase 2)


Additional Information