Metabolic and Hormonal Control of Phosphoenolpyruvate Carboxykinase and Malic Enzyme in Rat Liver.

Because of the strongly exergonic nature of glycolysis, the formation of carbohydrate from lactate and pyruvate does not proceed readily by direct reversal of the Embden-MeyerhofCori pathway (1). Additional energy for glycogen synthesis may be supplied at three separate steps: by hydrolysis of a sugar phosphate at the step fructose diphosphate + fructose 6-phosphate; by the utilization of uridine triphosphate for the conversion of glucose l-phosphate to glycogen; and by the formation of dicarboxylic acids from pyruvate followed by utilization of guanosine triphosphatc for forming phosphopyruvate from oxaloacetate. These key reactions must be under metabolic control, for their continued cyclic operation would lead to dissipation of energy. The nature of the hormonal and metabolic controls on enzymes affecting hexose diphosphate (cf. (2-5)), glycogen (cf. (6lo)), and malatc (11) has been investigated, but no similar studies have been reported for the enzymes that might be involved in formation of phosphopyruvate. Utter (12) has studied the concentration and distribution of phosphoenolpyruvate carboxykinase and the triphosphopyridine nucleotide-linked malic enzyme relative to pyruvic kinase in the rat and chicken. The extensive isotopic studies of Hastings et cd. (13, 14), Lorber et al. (15), Hoberman and D’Adamo (16), and more recently Bloom and Foster (17) have not been in complete agreement as to the extent of participation of the indirect V~TSUS direct or reversal pathway for carbohydrate synthesis. It was of interest to study the activity of phosphoenolpyruvate carboxykinase and the malic enzyme under various conditions which are known to alter carbohydrate metabolism. This communication presents the results of such an investigation. The data indicate that conditions leading to excess glucogenesis enhance phosphopyruvic carboxykinase but depress malic enzyme activity. The results suggest that malic enzyme is not responsible for the enhanced 14CO~ incorporation into carbohydrate that occurs in the diabetic animal (18).