Feedback Inhibition of Key Glycolytic Enzymes in Liver: Action of Free Fatty Acids

Increasing concentrations of sodium octanoate were progressively inhibitory to the activities of glucokinase, hexokinase, phosphofructokinase, and pyruvate kinase. Glucose-6-phosphate and 6-phosphogluconate dehydrogenases were also markedly inhibited. Other enzymes of carbohydrate metabolism such as lactate dehydrogenase, phosphohexose isomerase, and fructose-1,6-diphosphatase were not decreased. Among the key glycolytic enzymes, the inhibition of pyruvate kinase by the fatty acid was most marked. The biological significance of the inhibition of the key glycolytic enzymes is interpreted as a feedback inhibitory mechanism in regulation of fatty acid biosynthesis. The mechanism may function for rapid adaptation by which the organism can use the fatty acid level as a metabolic directional switch in decreasing glycolysis and turning on gluconeogenesis.

[1]  R. Kreisberg,et al.  Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[2]  P. D. Bewsher,et al.  Effects of Fat Mobilization on Liver Acetate Metabolism , 1966, Diabetes.

[3]  K. Taketa,et al.  The effect of palmityl coenzyme A on glucose 6-phosphate dehydrogenase and other enzymes. , 1966, The Journal of biological chemistry.

[4]  N. Ruderman,et al.  Non-hormonal factors in the control of gluconeogenesis. , 1966, Advances in enzyme regulation.

[5]  N. Stamm,et al.  Synchronous behavior pattern of key glycolytic enzymes: glucokinase, phosphofructokinase, and pyruvate kinase. , 1966, Advances in enzyme regulation.

[6]  O. Wieland,et al.  Effects of glucagon and long chain fatty acids on glucose production by isolated perfused rat liver. , 1966, Advances in enzyme regulation.

[7]  R. L. Singhal,et al.  Insulin: inducer of phosphofructokinase. The integrative action of insulin at the enzyme biosynthetic level. , 1965, Life sciences.

[8]  N. Stamm,et al.  Insulin: Inducer of Pyruvate Kinase , 1965, Science.

[9]  O. Wieland,et al.  Inhibition of glucose-6-phosphate dehydrogenase by long chain acyl-coenzyme A☆ , 1965 .

[10]  H. Krebs,et al.  ACCELERATION OF RENAL GLUCONEOGENESIS BY KETONE BODIES AND FATTY ACIDS. , 1965, The Biochemical journal.

[11]  R. L. Singhal,et al.  INSULIN: SUPPRESSOR OF BIOSYNTHESIS OF HEPATIC GLUCONEOGENIC ENZYMES. , 1965, Proceedings of the National Academy of Sciences of the United States of America.

[12]  H. Korchak,et al.  FREE FATTY ACIDS AS LIPOGENIC INHIBITORS. , 1964, Biochimica et biophysica acta.

[13]  P. Garland,et al.  Variations in tissue contents of coenzyme A thio esters and possible metabolic implications. , 1964, The Biochemical journal.

[14]  A. Freedman,et al.  Pyruvate Metabolism and Control: Factors Affecting Pyruvic Carboxylase Activity , 1964, Science.

[15]  C. Hales,et al.  Plasma glucose, non-esterified fatty acid and insulin concentrations in hypothalamic-hyperphagic rats. , 1964, The Biochemical journal.

[16]  S. R. Wagle Studies on pyruvate carboxylase activity in alloxan diabetic and normal animals. , 1964, Biochemical and biophysical research communications.

[17]  S. R. Wagle,et al.  Studies on gluconeogenesis. , 1964, Advances in enzyme regulation.

[18]  P. Ray,et al.  Metabolic and hormonal regulation of phosphopyruvate synthesis. , 1964, Advances in enzyme regulation.

[19]  A. Sols,et al.  Induced biosynthesis of liver glucokinase. , 1964, Advances in enzyme regulation.

[20]  H. Lardy,et al.  METABOLIC AND HORMONAL CONTROL OF PHOSPHOENOLPYRUVATE CARBOXYKINASE AND MALIC ENZYME IN RAT LIVER. , 1963, The Journal of biological chemistry.

[21]  J. Changeux,et al.  Allosteric proteins and cellular control systems. , 1963, Journal of molecular biology.

[22]  H. Morris,et al.  Comparative biochemistry of hepatomas. I. Carbohydrate enzymes in Morris hepatoma 5123. , 1961, Cancer research.

[23]  S. Weinhouse,et al.  Hepatic glucokinase in the fed, fasted, and alloxan-diabetic rat. , 1960, The Journal of biological chemistry.