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.
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 (PPARalpha) and is up-regulated in mouse liver in a PPARalpha-dependent manner.
Westin
Maria A K
MAK
From the Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry, C1-74, Karolinska University Hospital at Huddinge, SE-141 86 Stockholm, Sweden.
Hunt
Mary C
MC
From the Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry, C1-74, Karolinska University Hospital at Huddinge, SE-141 86 Stockholm, Sweden.
Alexson
Stefan E H
SEH
From the Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry, C1-74, Karolinska University Hospital at Huddinge, SE-141 86 Stockholm, Sweden. Electronic address: stefan.alexson@ki.se.
D000818:Animals; D001483:Base Sequence; D003065:Coenzyme A / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000502:physiology; D020675:Peroxisomes / Q000201:enzymology*; D010831:Phytanic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000502:physiology*
D005227:Fatty Acids; D047493:PPAR alpha; C089917:phytanoyl-coenzyme A; D010831:Phytanic Acid; C002844:pristanic acid; D013869:Thiolester Hydrolases; D003065:Coenzyme A