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Demonstration of dimethylnonanoyl-CoA thioesterase activity in rat liver peroxisomes followed by purification and molecular cloning of the thioesterase involved.
Biochem Biophys Res Commun. 2002 Jan 18; 290(2):629-34.BB

Abstract

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.

Authors+Show Affiliations

Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, 1100 DE, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11785945

Citation

Ofman, R, et al. "Demonstration of dimethylnonanoyl-CoA Thioesterase Activity in Rat Liver Peroxisomes Followed By Purification and Molecular Cloning of the Thioesterase Involved." Biochemical and Biophysical Research Communications, vol. 290, no. 2, 2002, pp. 629-34.
Ofman R, el Mrabet L, Dacremont G, et al. Demonstration of dimethylnonanoyl-CoA thioesterase activity in rat liver peroxisomes followed by purification and molecular cloning of the thioesterase involved. Biochem Biophys Res Commun. 2002;290(2):629-34.
Ofman, R., el Mrabet, L., Dacremont, G., Spijer, D., & Wanders, R. J. (2002). Demonstration of dimethylnonanoyl-CoA thioesterase activity in rat liver peroxisomes followed by purification and molecular cloning of the thioesterase involved. Biochemical and Biophysical Research Communications, 290(2), 629-34.
Ofman R, et al. Demonstration of dimethylnonanoyl-CoA Thioesterase Activity in Rat Liver Peroxisomes Followed By Purification and Molecular Cloning of the Thioesterase Involved. Biochem Biophys Res Commun. 2002 Jan 18;290(2):629-34. PubMed PMID: 11785945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Demonstration of dimethylnonanoyl-CoA thioesterase activity in rat liver peroxisomes followed by purification and molecular cloning of the thioesterase involved. AU - Ofman,R, AU - el Mrabet,L, AU - Dacremont,G, AU - Spijer,D, AU - Wanders,R J A, PY - 2002/1/12/pubmed PY - 2002/2/12/medline PY - 2002/1/12/entrez SP - 629 EP - 34 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 290 IS - 2 N2 - 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. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/11785945/Demonstration_of_dimethylnonanoyl_CoA_thioesterase_activity_in_rat_liver_peroxisomes_followed_by_purification_and_molecular_cloning_of_the_thioesterase_involved_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006291X0196245X DB - PRIME DP - Unbound Medicine ER -