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Originally published In Press as doi:10.1074/jbc.M703718200 on July 5, 2007

J. Biol. Chem., Vol. 282, Issue 37, 26707-26716, September 14, 2007
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Peroxisomes Contain a Specific Phytanoyl-CoA/Pristanoyl-CoA Thioesterase Acting as a Novel Auxiliary Enzyme in {alpha}- and beta-Oxidation of Methyl-branched Fatty Acids in Mouse*

Maria A. K. Westin, Mary C. Hunt, and Stefan E. H. Alexson1

From the From the Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry, C1-74, Karolinska University Hospital at Huddinge, SE-141 86 Stockholm, Sweden

Phytanic acid and pristanic acid are derived from phytol, which enter the body via the diet. Phytanic acid contains a methyl group in position three and, therefore, cannot undergo beta-oxidation directly but instead must first undergo {alpha}-oxidation to pristanic acid, which then enters beta-oxidation. Both these pathways occur in peroxisomes, and in this study we have identified a novel peroxisomal acyl-CoA thioesterase named ACOT6, which we show is specifically involved in phytanic acid and pristanic acid metabolism. Sequence analysis of ACOT6 revealed a putative peroxisomal targeting signal at the C-terminal end, and cellular localization experiments verified it as a peroxisomal enzyme. Subcellular fractionation experiments showed that peroxisomes contain by far the highest phytanoyl-CoA/pristanoyl-CoA thioesterase activity in the cell, which could be almost completely immunoprecipitated using an ACOT6 antibody. Acot6 mRNA was mainly expressed in white adipose tissue and was co-expressed in tissues with Acox3 (the pristanoyl-CoA oxidase). Furthermore, Acot6 was identified as a target gene of the peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) and is up-regulated in mouse liver in a PPAR{alpha}-dependent manner.


Received for publication, May 4, 2007 , and in revised form, June 20, 2007.

* This study was supported by the European Union Project "Peroxisomes," FP6 LSHG-CT-2004-512018, the Swedish Research Council, AFA sjukför-säkrings jubileumsstiftelse, Åke Wibergs stiftelse, Ruth och Richard Julins stiftelse, and Stiftelsen Professor Nanna Svartz fond. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed. Tel.: 46-8-585-812-74; Fax: 46-8-585-812-60; E-mail: stefan.alexson{at}ki.se.


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