Document Type

Article

Rights

This item is available under a Creative Commons License for non-commercial use only

Disciplines

Biochemistry and molecular biology

Publication Details

The Journal of Biological Chemistry (2004) 279 (21): 21,841-21,848. http://www.jbc.org/content/279/21/21841.long

Abstract

Peroxisomes are organelles that function in the b-oxidation of very-long and long-chain acyl-CoAs, bile acid-CoA intermediates, prostaglandins, leukotrienes, thromboxanes, dicarboxylic fatty acids, pristanic acid and xenobiotic carboxylic acids. The very long- and long-chain acyl-CoAs are mainly chain-shortened and then transported to mitochondria for further metabolism. We have now identified and characterized two peroxisomal acyl- CoA thioesterases, named PTE-Ia and PTE-Ic, which hydrolyze acyl-CoAs to the free fatty acid and coenzyme A. PTE-Ia and PTE-Ic show 82% sequence identity at amino acid level and a putative peroxisomal type 1 targeting signal of –AKL was identified at the carboxy-terminal end of both proteins. Localization experiments using green fluorescent fusion protein showed PTEIa and PTE-Ic to be localized in peroxisomes. Despite their high level of sequence identity, we show that PTE-Ia is mainly active on long-chain acyl- CoAs, while PTE-Ic is mainly active on medium-chain acyl-CoAs. Lack of regulation of enzyme activity by free CoASH suggests that PTE-Ia and PTE-Ic regulate intra-peroxisomal levels of acyl-CoA, and they may have a function in termination of b-oxidation of fatty acids of different chain-lengths. Tissue expression studies revealed that PTE-Ia is highly expressed in kidney, while PTE-Ic is most highly expressed in spleen, brain, testis and proximal and distal intestine. Both PTE-Ia and PTE-Ic were highly upregulated in mouse liver by treatment with the peroxisome proliferator WY-14,643 and by fasting, in a peroxisome proliferator-activated receptor alpha (PPARa) dependent manner. These data show that PTE-Ia and PTE-Ic have different functions based on different substrate specificities and tissue expression.