Conversion of Fatty Acids to Carbohydrate: Application of Isotopes to this Problem and Role of the Krebs Cycle as a Synthetic Pathway

Abstract

It was shown that fatty acid C become incorporated into glucose and that, in mammals, the major pathway by which such incorporation occurs is via acetyl-CoA, the Krebs cycle, decarboxylation of oxalacetate with the formation of phosphopyruvate, and the modified reversal of the Embden-Meyerhof scheme of glycolysis. A scheme was presented, and characterized mathematically, by which Krebs cycle C become available for synthetic reactions. From a survey of data it was shown that the Krebs cycle functioned as a synthetic as well as an oxidative pathway. It is quite clear, however, that fats cannot give rise to a net gain of carbohydrate in the same sense that carbohydrate yields a net gain of fat. Experiments with isotopes have served to illustrate a dynamic interrelation in which (1) acetate- and therefore fatty acids-contributes C to glucose formed via the Krebs cycle, or, in other words, acetate serves as a C source of glucose; (2) a non -acetate influx into the Krebs cycle makes possible the net formation of glucose via this cycle; (3) the interdependence of the above processes is reflected quantitatively in certain ratios, such as the one showing the recovery of labeled CO2 from carboxyl relative to that from methyl-labeled acetate.