Citrate as an Intermediary in the Inhibition of Phosphofructokinase in Rat Heart Muscle by Fatty Acids, Ketone Bodies, Pyruvate, Diabetes and Starvation

Abstract

IN perfused rat heart, glycolysis is accelerated by anoxia and uncouplers of respiratory chain phosphorylation and inhibited by the respiration of fatty acids, ketone bodies and pyruvate^1–4. Measurements of the concentrations of hexose phosphates have led to the suggestion that these agents change the rate of glycolysis by altering the rate of the phosphofructokinase step^1–3. The rates of glycolysis and of the phosphofructokinase reaction are also diminished in hearts from alloxan diabetic or starved rats in which the release of fatty acids from glycerides for oxidation is enhanced^4,5. In extracts of guinea pig heart⁶ and of rabbit skeletal muscle⁷ the activity of phosphofructokinase is inhibited by increasing concentrations of ATP and stimulated by increasing concentrations of 5′ AMP, cyclic 3′,5′ AMP, ADP and inorganic phosphate. These observations suggest that anoxia and uncouplers of respiratory chain phosphorylation increase the rate of the phosphofructokinase reaction in muscle (and hence of glycolysis) by increasing the concentrations of 5′ AMP, ADP and inorganic phosphate and diminishing that of ATP.