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Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism.
J Biol Chem. 2002 Jan 11; 277(2):1128-38.JB

Abstract

Peroxisomes function in beta-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. Here we have cloned and characterized a peroxisomal acyl-CoA thioesterase from mouse, named PTE-2 (peroxisomal acyl-CoA thioesterase 2). 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. 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 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.

Authors+Show Affiliations

Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. mary.hunt@chemlab.hs.sll.seNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11673457

Citation

Hunt, Mary C., et al. "Characterization of an acyl-coA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism." The Journal of Biological Chemistry, vol. 277, no. 2, 2002, pp. 1128-38.
Hunt MC, Solaas K, Kase BF, et al. Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism. J Biol Chem. 2002;277(2):1128-38.
Hunt, M. C., Solaas, K., Kase, B. F., & Alexson, S. E. (2002). Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism. The Journal of Biological Chemistry, 277(2), 1128-38.
Hunt MC, et al. Characterization of an acyl-coA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism. J Biol Chem. 2002 Jan 11;277(2):1128-38. PubMed PMID: 11673457.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of an acyl-coA thioesterase that functions as a major regulator of peroxisomal lipid metabolism. AU - Hunt,Mary C, AU - Solaas,Karianne, AU - Kase,B Frode, AU - Alexson,Stefan E H, Y1 - 2001/10/22/ PY - 2001/10/24/pubmed PY - 2002/2/8/medline PY - 2001/10/24/entrez SP - 1128 EP - 38 JF - The Journal of biological chemistry JO - J Biol Chem VL - 277 IS - 2 N2 - Peroxisomes function in beta-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. Here we have cloned and characterized a peroxisomal acyl-CoA thioesterase from mouse, named PTE-2 (peroxisomal acyl-CoA thioesterase 2). 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. 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 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11673457/Characterization_of_an_acyl_coA_thioesterase_that_functions_as_a_major_regulator_of_peroxisomal_lipid_metabolism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)87904-6 DB - PRIME DP - Unbound Medicine ER -