CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase
Mutations in human CGI-58/ABHD5 cause Chanarin-Dorfman syndrome (CDS), characterized by excessive storage of triacylglycerol in tissues. CGI-58 is an α/β-hydrolase fold enzyme expressed in all vertebrates. The carboxyl terminus includes a highly conserved consensus sequence (HXXXXD) for acyltransfer...
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doaj-ace0162c51bc47f6845228a87c2862a32021-04-28T05:55:22ZengElsevierJournal of Lipid Research0022-22752010-04-01514709719CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferaseGabriela Montero-Moran0Jorge M. Caviglia1Derek McMahon2Alexis Rothenberg3Vidya Subramanian4Zhi Xu5Samuel Lara-Gonzalez6Judith Storch7George M. Carman8Dawn L. Brasaemle9Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Department of Food Science, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901To whom correspondence should be addressed; Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901; Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Mutations in human CGI-58/ABHD5 cause Chanarin-Dorfman syndrome (CDS), characterized by excessive storage of triacylglycerol in tissues. CGI-58 is an α/β-hydrolase fold enzyme expressed in all vertebrates. The carboxyl terminus includes a highly conserved consensus sequence (HXXXXD) for acyltransferase activity. Mouse CGI-58 was expressed in Escherichia coli as a fusion protein with two amino terminal 6-histidine tags. Recombinant CGI-58 displayed acyl-CoA-dependent acyltransferase activity to lysophosphatidic acid, but not to other lysophospholipid or neutral glycerolipid acceptors. Production of phosphatidic acid increased with time and increasing concentrations of recombinant CGI-58 and was optimal between pH 7.0 and 8.5. The enzyme showed saturation kinetics with respect to 1-oleoyl-lysophosphatidic acid and oleoyl-CoA and preference for arachidonoyl-CoA and oleoyl-CoA. The enzyme showed slight preference for 1-oleoyl lysophosphatidic acid over 1-palmitoyl, 1-stearoyl, or 1-arachidonoyl lysophosphatidic acid. Recombinant CGI-58 showed intrinsic fluorescence for tryptophan that was quenched by the addition of 1-oleoyl-lysophosphatidic acid, oleoyl-CoA, arachidonoyl-CoA, and palmitoyl-CoA, but not by lysophosphatidyl choline. Expression of CGI-58 in fibroblasts from humans with CDS increased the incorporation of radiolabeled fatty acids released from the lipolysis of stored triacylglycerols into phospholipids. CGI-58 is a CoA-dependent lysophosphatidic acid acyltransferase that channels fatty acids released from the hydrolysis of stored triacylglycerols into phospholipids.http://www.sciencedirect.com/science/article/pii/S0022227520304818Chanarin-Dorfman Syndromeneutral lipid storage disorderα/β-hydrolase fold enzymes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gabriela Montero-Moran Jorge M. Caviglia Derek McMahon Alexis Rothenberg Vidya Subramanian Zhi Xu Samuel Lara-Gonzalez Judith Storch George M. Carman Dawn L. Brasaemle |
spellingShingle |
Gabriela Montero-Moran Jorge M. Caviglia Derek McMahon Alexis Rothenberg Vidya Subramanian Zhi Xu Samuel Lara-Gonzalez Judith Storch George M. Carman Dawn L. Brasaemle CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase Journal of Lipid Research Chanarin-Dorfman Syndrome neutral lipid storage disorder α/β-hydrolase fold enzymes |
author_facet |
Gabriela Montero-Moran Jorge M. Caviglia Derek McMahon Alexis Rothenberg Vidya Subramanian Zhi Xu Samuel Lara-Gonzalez Judith Storch George M. Carman Dawn L. Brasaemle |
author_sort |
Gabriela Montero-Moran |
title |
CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase |
title_short |
CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase |
title_full |
CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase |
title_fullStr |
CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase |
title_full_unstemmed |
CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase |
title_sort |
cgi-58/abhd5 is a coenzyme a-dependent lysophosphatidic acid acyltransferase |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2010-04-01 |
description |
Mutations in human CGI-58/ABHD5 cause Chanarin-Dorfman syndrome (CDS), characterized by excessive storage of triacylglycerol in tissues. CGI-58 is an α/β-hydrolase fold enzyme expressed in all vertebrates. The carboxyl terminus includes a highly conserved consensus sequence (HXXXXD) for acyltransferase activity. Mouse CGI-58 was expressed in Escherichia coli as a fusion protein with two amino terminal 6-histidine tags. Recombinant CGI-58 displayed acyl-CoA-dependent acyltransferase activity to lysophosphatidic acid, but not to other lysophospholipid or neutral glycerolipid acceptors. Production of phosphatidic acid increased with time and increasing concentrations of recombinant CGI-58 and was optimal between pH 7.0 and 8.5. The enzyme showed saturation kinetics with respect to 1-oleoyl-lysophosphatidic acid and oleoyl-CoA and preference for arachidonoyl-CoA and oleoyl-CoA. The enzyme showed slight preference for 1-oleoyl lysophosphatidic acid over 1-palmitoyl, 1-stearoyl, or 1-arachidonoyl lysophosphatidic acid. Recombinant CGI-58 showed intrinsic fluorescence for tryptophan that was quenched by the addition of 1-oleoyl-lysophosphatidic acid, oleoyl-CoA, arachidonoyl-CoA, and palmitoyl-CoA, but not by lysophosphatidyl choline. Expression of CGI-58 in fibroblasts from humans with CDS increased the incorporation of radiolabeled fatty acids released from the lipolysis of stored triacylglycerols into phospholipids. CGI-58 is a CoA-dependent lysophosphatidic acid acyltransferase that channels fatty acids released from the hydrolysis of stored triacylglycerols into phospholipids. |
topic |
Chanarin-Dorfman Syndrome neutral lipid storage disorder α/β-hydrolase fold enzymes |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520304818 |
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