The Concentration of Malonyl-Coenzyme A and the Control of Fatty Acid Synthesis in Vivo

作者：Robert W. Guynn, Dulce Veloso, Richard L. Veech · 发表于：Journal of Biological Chemistry · 年份：1972 · DOI：10.1016/s0021-9258(19)44633-4 · 被引用次数：182 · 研究领域：Mitochondrial Function and Pathology、Metabolism and Genetic Disorders、Diet and metabolism studies

An enzymatic method has been developed for the measurement of malonyl-CoA in perchloric acid extracts of liver. With this method the relative activities of acetyl-CoA carboxylase and fatty acid synthetase have been studied in vivo by comparing the diet-induced changes in malonyl-CoA concentrations with rates of 3H2O incorporation into fatty acids. Malonyl-CoA concentrations were low in the fat-fed or 48-hours starved animal (0.004 to 0.006 µmole per g wet weight) but approached normal-fed levels (0.013 µmole per g wet weight) within 3 hours of refeeding the starved animal. The highest concentrations of malonyl-CoA (0.025 µmole per g wet weight) were found in the meal-fed animal. The de novo rates of fatty acid synthesis in vivo varied between 0.02 µmole of C2 units per min per g wet weight of liver in the starved or fat-fed animals to 0.45 µmole, of C2 units per min per g in the meal-fed group. Malonyl-CoA concentrations and the rate of tritium incorporation into fatty acids were increased above starved values in all fed groups except that group fed a high fat diet. A number of intermediary metabolites which have been proposed as controllers of the rates of fatty acid synthesis have been measured in freeze-clamped liver. There was no correlation between the rate of fatty acid synthesis and the liver content of citrate, ATP, ADP, glucose, glucose 6-phosphate, or α-glycerophosphate. In addition, short term control did not appear to be exerted by free mitochondrial [NAD+]:[NADH]...