Effect of CO2 Concentration on Intermediates of the Embden-Myerhof Pathway and the Citric Acid Cycle in Isolated Perfused Rat Liver

Abstract

Abstract The effect of variation of total CO2 concentration at constant pH on the intermediates of the Embden-Meyerhof pathway and citric acid cycle in the isolated perfused liver has been studied. Total CO2 concentration of the perfusate was changed either from 10 to 34 mm or from 34 to 10 mm at pH 7.40 at the midpoint of 2-hour liver perfusions. In livers perfused with a medium containing 14 mm glycerol and 17 mm glucose, the liver concentration of glucose-6-P, fructose-6-P, fructose diphosphate, pyruvate, malate, and citrate was found to have increased when CO2 concentration was increased, and decreased when CO2 concentration was decreased, in a range of 6 to 59%, when compared to control values. The tissue concentration of 3-P-glycerate, P-enolpyruvate, and aspartate changed in an inverse manner, decreasing and increasing in a range of 12 to 104% as the CO2 concentration of the liver perfusate was increased and decreased, respectively. Livers perfused with a medium to which glucose (5.8 mm) was the only added substrate were found to have generally similar changes in metabolite concentrations with change in CO2 concentration. Citrate and pyruvate concentrations were, however, more markedly altered and the change in malate concentration was opposite in direction, with respect to the change in the CO2 concentration of the perfusate, and greater than that observed when both glycerol (14 mm) and glucose (17 mm) were present in the perfusate. Livers perfused with medium containing the combined higher concentrations of glycerol and glucose had higher absolute levels of glucose-6-P, fructose-6-P, fructose diphosphate, 3-P-glycerate, P-enolpyruvate, and pyruvate and lower malate, aspartate, and citrate concentrations at both CO2 concentrations. The results of this study support the concept that physiological changes in extracellular CO2 concentration markedly alter the concentration of metabolic intermediates associated directly with carbohydrate and lipid metabolism.