Inhibition of diacylglycerol acyltransferase by 2-bromooctanoate in cultured rat hepatocytes.
Triacylglycerol synthesis in cultured rat hepatocytes was inhibited by 2-bromooctanoate with a concomitant accumulation of diacylglycerols. 2-Bromooctanoate inhibition could be ascribed to its thioesterification by medium chain fatty acyl-CoA synthase (Raaka, B.M., and Lowenstein, J.M. (1979) J. Biol. Chem. 254, 6755-6762) with 2-bromooctanoyl-CoA acting as a competitive inhibitor of diacylglycerol acyltransferase. The Ki of 2-bromooctanoyl-CoA was 1.5 microM compared with a Km of 25 microM for the palmitoyl-CoA substrate. Diacylglycerol esterification was also inhibited by C12-C16 2-bromo fatty acids. However, inhibition of triacylglycerol synthesis by long chain 2-bromo fatty acids was accompanied by decreased overall neutral lipid synthesis as a result of inhibition of the long chain fatty acyl-CoA synthase. Since 2-bromooctanoate was a poor inhibitor of the long chain fatty acyl-CoA synthase, it appears to function selectively as an inhibitor of diacylglycerol acyltransferase in cultured rat hepatocytes.
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D002478:Cells, Cultured; D051048:Diacylglycerol O-Acyltransferase; D005990:Glycerol / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000096:biosynthesis
D002210:Caprylates; D010168:Palmitates; D014280:Triglycerides; C019279:2-bromooctanoic acid; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; D005990:Glycerol