Production Of malonyl-CoA Research Articles

Coordinate Suppression of Liver Acetyl-CoA Carboxylase and Fatty Acid Synthetase by Polyunsaturated Fat

Polyunsaturated fats (PUFA) suppressed hepatic fatty acid synthesis and the activities of lipogenic enzymes more effectively than did saturated fats. The activity of glycolytic enzymes—glucokinase, phosphofructokinase and pyruvate kinase—were not affected by PUFA. The absolute rate of liver fatty acid synthesis after meal ingestion was very similar to the maximal activities of acetyl-CoA carboxylase and fatty acid synthetase. When PUFA was supplemented to a fat-free diet, the activities of carboxylase and synthetase decreased similarly over 3 days. During the 3 days, the concentration of liver malonyl-CoA (after meal ingestion) did not significantly differ between the fat-free and PUFA dietary treatments. Apparently PUFA feeding caused a coordinate decrease in the utilization and production of malonyl-CoA which resulted in no net change in malonyl-CoA pool size. Thus the mechanism by which PUFA suppresses fatty acid synthesis appears to be by coordinately and specifically reducing the amount of carboxylase and fatty acid synthetase.lipogenesis polyunsaturated fats

Fatty acid biosynthesis in Erlich cells. The mechanism of short term control by exogenous free fatty acids.

We have examined the mechanism by which extracellular free fatty acids regulate fatty acid biosynthesis in Ehrlich ascites tumor cells. De novo biosynthesis in intact cells was inhibited by stearate greater than oleate greater than palmitate greater than linoleate. The amount of citrate and long chain acyl-CoA in the cells was not changed appreciably by the addition of free fatty acids to the incubation medium, indicating than free fatty acids do not regulate fatty acid biosynthesis by changing the total intracellular content of these metabolites. By measuring the incorporation of labeled free fatty acids into acyl-CoA, however, it was determined that the fatty acid composition of the acyl-CoA poolwas changed dramatically to reflect the composition of the exogenous free fatty acids. The relative inhibitory effects of different free fatty acids appear to depend on the ability of their acyl-CoA derivatives to regulate acyl-CoA carboxylase activity. The acyl-CoA concentration needed to produce 50% inhibition of purified Ehrlich cell carboxylase was found to be 0.68 mum for stearoyl-CoA, 1.6 mum for oleoyl-CoA, 2.2 mum for palmitoyl-CoA, 23 mum for myristoyl-CoA, 30 mum for lauroyl-CoA, and 37 mum for linoleoyl-CoA. In contrast to their effects on de novo synthesis, all of the free fatty acids added except stearate stimulated chain elongation in intact cells. Microsomal chain elongation, the major system for elongation in Ehrlich cells, also was regulated by the composition of the cellular acyl-CoA pool. Lauroyl-CoA, myristoyl-CoA, and palmitoyl-CoA were good substrates for elongation by isolated microsomes; oleoyl-CoA, and linoleoyl-CoA were intermediate; and stearoyl-CoA was a very poor substrate. We conclude that free fatty acids regulate fatty acid biosynthesis by changing the composition of the cellular acyl-CoA pool. These changes control the rate of malonyl-CoA production and, because of the acyl-CoA substrate specificity of the microsomal elongation system, modulate the amount of malonyl-CoA used for chain elongation.