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
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 t...
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| Published in | The Journal of biological chemistry Vol. 282; no. 37; pp. 26707 - 26716 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
14.09.2007
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| Abstract | 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. |
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| AbstractList | 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. 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. |
| Author | Alexson, Stefan E.H. Westin, Maria A.K. Hunt, Mary C. |
| Author_xml | – sequence: 1 givenname: Maria A.K. surname: Westin fullname: Westin, Maria A.K. – sequence: 2 givenname: Mary C. surname: Hunt fullname: Hunt, Mary C. – sequence: 3 givenname: Stefan E.H. surname: Alexson fullname: Alexson, Stefan E.H. email: stefan.alexson@ki.se |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17613526$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:115884153$$DView record from Swedish Publication Index |
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| SubjectTerms | 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 |
| Title | 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 |
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