RGD Reference Report - Demonstration of Dimethylnonanoyl-CoA Thioesterase Activity in Rat Liver Peroxisomes Followed by Purification and Molecular Cloning of the Thioesterase Involved.

General

Demonstration of Dimethylnonanoyl-CoA Thioesterase Activity in Rat Liver Peroxisomes Followed by Purification and Molecular Cloning of the Thioesterase Involved.
Authors:	Ofman, R El Mrabet, L Dacremont, G Spijer, D Wanders, RJ
Citation:	Ofman R, etal., Biochem Biophys Res Commun 2002 Jan 18;290(2):629-34.
RGD ID:	70235
Pubmed:	PMID:11785945 (View Abstract at PubMed)
DOI:	DOI:10.1006/bbrc.2001.6245 (Journal Full-text)
Peroxisomes play an indispensable role in cellular fatty acid oxidation in higher eukaryotes by catalyzing the chain shortening of a distinct set of fatty acids and fatty acid derivatives including pristanic acid (2,6,10,14-tetramethylpentadecanoic acid). Earlier studies have shown that pristanic acid undergoes three cycles of beta-oxidation in peroxisomes to produce 4,8-dimethylnonanoyl-CoA (DMN-CoA) which is then transported to the mitochondria for full oxidation to CO(2) and H(2)O. In principle, this can be done via two different mechanisms in which DMN-CoA is either converted into the corresponding carnitine ester or hydrolyzed to 4,8-dimethylnonanoic acid plus CoASH. The latter pathway can only be operational if peroxisomes contain 4,8-dimethylnonanoyl-CoA thioesterase activity. In this paper we show that rat liver peroxisomes indeed contain 4,8-dimethylnonanoyl-CoA thioesterase activity. We have partially purified the enzyme involved from peroxisomes and identified the protein as the rat ortholog of a known human thioesterase using MALDI-TOF mass spectrometry in combination with the rat EST database. Heterologous expression studies in Escherichia coli established that the enzyme hydrolyzes not only DMN-CoA but also other branched-chain acyl-CoAs as well as straight-chain acyl-CoA-esters. Our data provide convincing evidence for the existence of the second pathway of acyl-CoA transport from peroxisomes to mitochondria by hydrolysis of the CoA-ester in peroxisomes followed by transport of the free acid to mitochondria, reactivation to its CoA-ester, and oxidation to CO(2) and H(2)O. (c)2002 Elsevier Science.

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Biological Process

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
acyl-CoA metabolic process	involved_in	IDA		70235	PMID:11785945	UniProt

Cellular Component

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
peroxisome	located_in	IDA		70235	PMID:11785945	UniProt

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
choloyl-CoA hydrolase activity	enables	IDA		70235	PMID:11785945	UniProt
fatty acyl-CoA hydrolase activity	enables	IDA		70235	PMID:11785945	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Acot8 (acyl-CoA thioesterase 8)

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Demonstration of Dimethylnonanoyl-CoA Thioesterase Activity in Rat Liver Peroxisomes Followed by Purification and Molecular Cloning of the Thioesterase Involved.