Document Detail


Thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (Acot13): a homotetrameric hotdog fold thioesterase with selectivity for long-chain fatty acyl-CoAs.
MedLine Citation:
PMID:  19405909     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jie Wei; Hye Won Kang; David E Cohen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-06-26
Journal Detail:
Title:  The Biochemical journal     Volume:  421     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-25     Completed Date:  2009-11-05     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  311-22     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acyl Coenzyme A / 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:
DK-48873/DK/NIDDK NIH HHS; DK-56626/DK/NIDDK NIH HHS; R01 DK048873/DK/NIDDK NIH HHS; R01 DK048873-14/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:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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