Peroxisomes Contain a Specific Phytanoyl-CoA/Pristanoyl-CoA Thioesterase Acting as a Novel Auxiliary Enzyme in α- and β-Oxidation of Methyl-branched Fatty Acids in Mouse

• Published in: The Journal of biological chemistry Vol. 282; no. 37; pp. 26707 - 26716
• Main Authors: Westin, Maria A.K., Hunt, Mary C., Alexson, Stefan E.H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.09.2007
• Subjects: Animals; Base Sequence; Coenzyme A - metabolism; Fatty Acids - metabolism; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Oxidation-Reduction; Peroxisomes - enzymology; Phytanic Acid - analogs & derivatives; Phytanic Acid - metabolism; PPAR alpha - physiology; Thiolester Hydrolases - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M703718200

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 β-oxidation directly but instead must first undergo α-oxidation to pristanic acid, which then enters β-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 α (PPARα) and is up-regulated in mouse liver in a PPARα-dependent manner.