| Thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (Acot13): a homotetrameric hotdog fold thioesterase with selectivity for long-chain fatty acyl-CoAs. | |
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MedLine Citation:
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PMID: 19405909 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Them2 (thioesterase superfamily member 2) is a 140-amino-acid protein of unknown biological function that comprises a single hotdog fold thioesterase domain. On the basis of its putative association with mitochondria, accentuated expression in oxidative tissues and interaction with StarD2 (also known as phosphatidylcholine-transfer protein, PC-TP), a regulator of fatty acid metabolism, we explored whether Them2 functions as a physiologically relevant fatty acyl-CoA thioesterase. In solution, Them2 formed a stable homotetramer, which denatured in a single transition at 59.3 degrees C. Them2 exhibited thioesterase activity for medium- and long-chain acyl-CoAs, with Km values that decreased exponentially as a function of increasing acyl chain length. Steady-state kinetic parameters for Them2 were characteristic of long-chain mammalian acyl-CoA thioesterases, with minimal values of Km and maximal values of kcat/Km observed for myristoyl-CoA and palmitoyl-CoA. For these acyl-CoAs, substrate inhibition was observed when concentrations approached their critical micellar concentrations. The acyl-CoA thioesterase activity of Them2 was optimized at physiological temperature, ionic strength and pH. For both myristoyl-CoA and palmitoyl-CoA, the addition of StarD2 increased the kcat of Them2. Enzymatic activity was decreased by the addition of phosphatidic acid/phosphatidylcholine small unilamellar vesicles. Them2 expression, which was most pronounced in mouse heart, was associated with mitochondria and was induced by activation of PPARalpha (peroxisome-proliferator-activated receptor alpha). We conclude that, under biological conditions, Them2 probably functions as a homotetrameric long-chain acyl-CoA thioesterase. Accordingly, Them2 has been designated as the 13th member of the mammalian acyl-CoA thioesterase family, Acot13. |
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Authors:
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Jie Wei; Hye Won Kang; David E Cohen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-06-26 |
Journal Detail:
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Title: The Biochemical journal Volume: 421 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-06-25 Completed Date: 2009-11-05 Revised Date: 2013-03-13 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 311-22 Citation Subset: IM |
Affiliation:
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Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acyl Coenzyme A
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chemistry,
metabolism* Animals Hydrogen-Ion Concentration Kinetics Lipid Metabolism Male Mice Mice, Inbred Strains Osmolar Concentration Protein Folding Substrate Specificity Temperature Thiolester Hydrolases / chemistry*, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK-48873/DK/NIDDK NIH HHS; DK-56626/DK/NIDDK NIH HHS; R01 DK048873-14/DK/NIDDK NIH HHS; R01 DK048873-16/DK/NIDDK NIH HHS; R01 DK056626/DK/NIDDK NIH HHS; R01 DK056626-10/DK/NIDDK NIH HHS; R37 DK048873/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acyl Coenzyme A; 3130-72-1/S-tetradecanoyl-coenzyme A; EC 3.1.2.-/ACOT13 protein, human; EC 3.1.2.-/Acot13 protein, mouse; EC 3.1.2.-/Thiolester Hydrolases |
| Comments/Corrections | |
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