Hepatic sn-glycerol-3-phosphate acyltransferases: Effect of monoacylglycerol analogs on mitochondrial and microsomal activities

Abstract

The regulation of cellular diacylglycerol levels may have important consequences for protein kinase C activity. Because monoacylglycerols were said to inhibit the committed step of glycerolipid synthesis, the sn-glycerol-3- p acyltransferase (glycerol- P acyltransferase), we determined (1) whether both the mitochondrial and the microsomal glycerol- P acyltransferase isoenzymes were inhibited by 1- and 2-mono-18:1-glycerols and their ether and amide analogs and (2) what the mechanism of inhibition was. 1- and 2-mono-18:1-glycerols, their ether and amide analogs, and l-mono-18:1-glycerol 3-phosphate were all competitive inhibitors of the microsomal glycerol- P acyltransferase activity. The relative K i values suggested that inhibition was strongest with the radyl group at the sn-1 position and that an oxygen bond is important at the sn-1 position. Although the monoacyl- and monoalkylglycerols were also competitive inhibitors of the mitochondrial glycerol- p acyltransferase, neither of the amide analogs was an inhibitor, suggesting that an oxygen bond is essential at both the sn-1 and sn-2 positions. Because monoradylglycerols inhibit several enzyme activities that contribute to the biosynthesis or the metabolism of diacylglycerol, these inhibitors may function within cells in part to regulate cellular diacylglycerol levels.