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Biochemistry and molecular biology
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 b-oxidation directly, but instead must first undergo a-oxidation to pristanic acid, which then enters b-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 coexpressed in tissues with Acox 3 (the pristanoyl-CoA oxidase). Furthermore, Acot6 was identified as a target gene of the PPARa and is upregulated in mouse liver in a PPARa dependent manner.
Westin, A., Hunt, M., Alexson, S. (2007) 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. Journal of Biological Chemistry, 2007 282: 26707-26716. doi:10.1074/jbc.M703718200