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


Biochemistry and molecular biology

Publication Details

The Journal of Biological Chemistry,J. Biol. Chem. 2002 277: 1128-1138. Available from the publisher here⊂mit=yes


Peroxisomes function in b-oxidation of very long- and long-chain fatty acids, dicarboxylic fatty acids, bile acid intermediates, prostaglandins, leukotrienes, thromboxanes, pristanic acid and xenobiotic carboxylic acids. These lipids are mainly chain-shortened for excretion as the carboxylic acids or transported to mitochondria for further metabolism. Several of these carboxylic acids are slowly oxidized and may therefore sequester coenzyme A (CoASH). To prevent CoASH sequestration and to facilitate excretion of chain-shortened carboxylic acids, acyl-CoA thioesterases, which catalyze the hydrolysis of acyl-CoAs to the free acid and CoASH, may play important roles. We have here cloned and characterized a peroxisomal acyl-CoA thioesterase from mouse, named PTE-2, which was first isolated as a HIV-1 Nef binding protein in human (Liu et al. J. Biol. Chem. (1997) 272, 13779-13785, Watanabe et al. Biochem. Biophys. Res. Comm. (1997) 238, 234-239). PTE-2 is ubiquitously expressed and induced at mRNA level by treatment with the peroxisome proliferator WY-14,643 and fasting. Induction seen by these treatments was dependent on the peroxisome proliferator-activated receptor alpha (PPARa). Recombinant PTE-2 showed a broad chain-length specificity with acyl-CoAs from short- and medium-, to long-chain acyl- CoAs, and other substrates including trihydroxycoprostanoyl-CoA, hydroxymethylglutaryl-CoA and branched chain acyl-CoAs, all of which are present in peroxisomes. Highest activities were found with the CoA esters of primary bile acids choloyl-CoA and chenodeoxycholoyl-CoA as substrates. PTE-2 activity is inhibited by free CoASH, suggesting that intraperoxisomal free CoASH levels regulate the activity of this enzyme. The acyl-CoA specificity of recombinant PTE-2 closely resembles that of purified mouse liver peroxisomes, suggesting that PTE-2 is the major acyl-CoA thioesterase in peroxisomes. Addition of recombinant PTE-2 to incubations containing isolated mouse liver peroxisomes strongly inhibited bile 3 acid-CoA: amino acid N-acyltransferase activity, suggesting that this thioesterase can interfere with CoASH-dependent pathways. We propose that PTE-2 functions as a key regulator of peroxisomal lipid metabolism.