Effect of glutathione deficiency on the adipocyte sn-glycerol-3-phosphate acyltransferase. 1998

S C Jamdar, and E Soo, and W F Cao
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.

The present study investigates the effects of various glutathione (GSH) depleting agents on sn-glycerol-3-phosphate acyltransferase (GPAT) activity, the first committed step in adipose triacylglycerol formation. GPAT activity was measured in the presence of [14C]glycerol-3-phosphate and palmitoyl-CoA, using different subcellular fractions. Glutathione deficiency in animals was induced in the presence of diethylmaleate (DEM) or buthionine sulfoximine. In this respect, DEM (1.75 mmoles/kg) was more effective and caused over 75% decrease in GPAT activity within 4 h of DEM administration. Further studies indicated that this decrease in GPAT activity was mainly related to the microsomal form of GPAT, without any significant effect on mitochondrial GPAT activity. Adipocytes incubated with 2.5 mm DEM for 1 h at 37 degrees C also showed a reduction in the adipocyte glutathione content, which was accompanied by decreases in GPAT activity. The effect of DEM on adipocyte GPAT activity was partially reversible in the presence of cell permeable glutathione ethyl ester. Preincubation of adipose tissue homogenates with 2.5 mM DEM at 30 degrees C for 45 min also showed a significant loss of the GPAT activity. The presence of 5 mM dithiothreitol in the preincubation mixture offered a significant protection of the GPAT activity against DEM. However, glutathione was ineffective in this respect as it interfered with the utilization of palmitoyl-CoA in the GPAT assay. Therefore, on the basis of these three different approaches, the present studies suggest that the thiol environment offered by glutathione (in vivo and in vitro studies) or dithiothreitol (in a cell-free system) is critical for the maintenance of GPAT activity.

UI MeSH Term Description Entries
D008297 Male Males
D008298 Maleates Derivatives of maleic acid (the structural formula (COO-)-C
D008861 Microsomes Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) Microsome
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D005992 Glycerol-3-Phosphate O-Acyltransferase An enzyme that transfers acyl groups from acyl-CoA to glycerol-3-phosphate to form monoglyceride phosphates. It acts only with CoA derivatives of fatty acids of chain length above C-10. Also forms diglyceride phosphates. EC 2.3.1.15. Glycerolphosphate Acyltransferase,Stearyl-CoA Glycerophosphate Transstearylase,Acyl-CoA Sn-Glycerol-3-Phosphate-O-Acyltransferase,Glycerophosphate Acyltransferase,Acyl CoA Sn Glycerol 3 Phosphate O Acyltransferase,Acyltransferase, Glycerolphosphate,Acyltransferase, Glycerophosphate,Glycerol 3 Phosphate O Acyltransferase,Glycerophosphate Transstearylase, Stearyl-CoA,O-Acyltransferase, Glycerol-3-Phosphate,Sn-Glycerol-3-Phosphate-O-Acyltransferase, Acyl-CoA,Stearyl CoA Glycerophosphate Transstearylase,Transstearylase, Stearyl-CoA Glycerophosphate
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017667 Adipocytes Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals. Fat Cells,Lipocytes,Adipocyte,Cell, Fat,Cells, Fat,Fat Cell,Lipocyte
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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