Oleate stimulation of diacylglycerol formation from phosphatidylcholine through effects on phospholipase D and phosphatidate phosphohydrolase.
Hydrolysis of exogenous phosphatidylcholine (PtdCho) to 1,2-diacylglycerol by rat liver plasma membranes was stimulated by oleate concentrations as low as 0.1 mM. In the presence of 75 mM ethanol, the fatty acid also enhanced phosphatidylethanol (PtdEtOH) formation from PtdCho. These effects were also observed with linoleate and arachidonate, but not with saturated fatty acids or detergents, and were minimal in microsomes or mitochondria. Release of [3H]choline from exogenous Ptd[3H]Cho was stimulated by oleate, whereas phosphoryl[3H]choline formation was inhibited. Oleate and other unsaturated, but not saturated, fatty acids also stimulated the conversion of exogenous [14C]phosphatidic acid to [14C]diacylglycerol. These data are consistent with stimulatory effects of these fatty acids on both phospholipase D and phosphatidate phosphohydrolase in liver plasma membranes. The stimulatory effect of guanosine 5'-O-[3-thio]triphosphate) (20 microM) on PtdEtOH and diacylglycerol formation from PtdCho was enhanced by low concentrations of oleate. Phospholipase A2 also stimulated PtdEtOH and diacylglycerol formation from exogenous PtdCho. It is proposed that unsaturated fatty acids may play a physiological role in the regulation of diacylglycerol production through activation of phospholipase D and phosphatidate phosphohydrolase.
Siddiqui
R A
RA
Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville 37232.
Exton
J H
JH
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004075:Diglycerides / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology; D020404:Glycerophospholipids; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006868:Hydrolysis; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010711:Phosphatidate Phosphatase / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism*; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats
C011439:1,2-diacylglycerol; D004075:Diglycerides; D005227:Fatty Acids; D020404:Glycerophospholipids; D009829:Oleic Acids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; C051521:phosphatidylethanol; D019301:Oleic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010741:Phospholipases A; D054467:Phospholipases A2; D010711:Phosphatidate Phosphatase; D010739:Phospholipase D