Rutgers Center for Lipid Research
Rutgers Center for Lipid Research
Montero-Moran G.,Rutgers Center for Lipid Research |
Caviglia J.M.,Rutgers Center for Lipid Research |
Caviglia J.M.,Columbia University |
McMahon D.,Rutgers Center for Lipid Research |
And 5 more authors.
Journal of Lipid Research | Year: 2010
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 fl uorescence 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 fi broblasts 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. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.
Lagakos W.S.,Rutgers University |
Lagakos W.S.,Rutgers Center for Lipid Research |
Gajda A.M.,Rutgers University |
Gajda A.M.,Rutgers Center for Lipid Research |
And 8 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2011
It has long been known that mammalian enterocytes coexpress two members of the fatty acidbinding protein (FABP) family, the intestinal FABP (IFABP) and the liver FABP (LFABP). Both bind long-chain fatty acids and have similar though not identical distributions in the intestinal tract. While a number of in vitro properties suggest the potential for different functions, the underlying reasons for expression of both proteins in the same cells are not known. Utilizing mice genetically lacking either IFABP or LFABP, we directly demonstrate that each of the enterocyte FABPs participates in specific pathways of intestinal lipid metabolism. In particular, LFABP appears to target fatty acids toward oxidative pathways and dietary monoacylglycerols toward anabolic pathways, while IFABP targets dietary fatty acids toward triacylglycerol synthesis. The two FABP-null models also displayed differences in whole body response to fasting, with LFABP-null animals losing less fat-free mass and IFABP-null animals losing more fat mass relative to wild-type mice. The metabolic changes observed in both null models appear to occur by nontranscriptional mechanisms, supporting the hypothesis that the enterocyte FABPs are specifically trafficking their ligands to their respective metabolic fates. © 2011 the American Physiological Society.
McCauliff L.A.,Rutgers Center for Lipid Research |
Xu Z.,Rutgers Center for Lipid Research |
Li R.,Rutgers Center for Lipid Research |
Kodukula S.,Rutgers Center for Lipid Research |
And 4 more authors.
Journal of Biological Chemistry | Year: 2015
Background: Niemann-Pick C2 (NPC2) protein is essential for intracellular cholesterol trafficking. Results: Several regions on the surface of NPC2 are integral to its cholesterol transfer properties, which include the promotion of membrane-membrane interactions. Conclusion: Rapid cholesterol transfer occurs via NPC2-mediated membrane interactions. Significance: NPC2 may promote rapid efflux of late endosomal/lysosomal cholesterol by functioning at intra-lysosomal membrane contact sites. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.