CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase

被引:79
作者
Montero-Moran, Gabriela [1 ,2 ]
Caviglia, Jorge M. [1 ,2 ]
McMahon, Derek [1 ,2 ]
Rothenberg, Alexis [2 ]
Subramanian, Vidya [2 ]
Xu, Zhi [1 ,2 ]
Lara-Gonzalez, Samuel [4 ]
Storch, Judith [1 ,2 ]
Carman, George M. [1 ,3 ]
Brasaemle, Dawn L. [1 ,2 ]
机构
[1] Rutgers State Univ, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA
[2] Rutgers State Univ, Dept Nutrit Sci, New Brunswick, NJ 08901 USA
[3] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA
[4] Rutgers State Univ, Dept Chem & Chem Biol, New Brunswick, NJ 08901 USA
基金
美国国家卫生研究院;
关键词
Chanarin-Dorfman Syndrome; neutral lipid storage disorder; alpha/beta-hydrolase fold enzymes; LIPID STORAGE DISEASE; ADIPOSE TRIGLYCERIDE LIPASE; CHANARIN-DORFMAN-SYNDROME; CRITICAL MICELLAR CONCENTRATIONS; HORMONE-SENSITIVE LIPASE; FATTY ACYL-COA; TRIACSIN-C; DROPLETS; LIPOLYSIS; TRIACYLGLYCEROL;
D O I
10.1194/jlr.M001917
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mutations in human CGI-58/ABHD5 cause Chanarin-Dorfman syndrome (CDS), characterized by excessive storage of triacylglycerol in tissues. CGI-58 is an alpha/beta-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.-Montero-Moran, G., J. M. Caviglia, D. McMahon, A. Rothenberg, V. Suramanian, Z. Xu, S. Lara-Gonzalez, J. Storch, G. M. Carman, and D. L. Brasaemle. CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase. J. Lipid Res. 2010. 51: 709-719.
引用
收藏
页码:709 / 719
页数:11
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