Activation of Liver Pyruvate Kinase by Fructose 1,6-Diphosphate

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Abstract
The main kinetic characteristics of the stimulation of pyruvate kinase by FDP [fructose 1,6-diphosphate] are the homotropic co-operative interaction exhibited by both substrate (PEP) and effector (FDP), the abolition of the substrate-substrate interaction at high concentrations of FDP (heterotropic interaction) and the tenfold decrease in the apparent Km for PEP. The loss of FDP homotropic interaction at high concentrations of PEP was less clearly demonstrated but may certainly be present. These are clearly the characteristics of an allosteric system (Monod, Wyman and Changeux, 1965). In terms of the Monod allosteric model these data indicate a "positive K system", i.e. one in which both substrate and effector have differential affinities for the two hypothetical forms of the enzyme R and T. The absence of stimulation of muscle pyruvate kinase by FDP should make it of interest to compare its structure and properties with those of the liver enzyme. It is possible that muscle pyruvate kinase in situ has allosteric properties similar to those of yeast and liver pyruvate kinase, but that these are lost consequent to changes in quaternary structure during extraction and purification. The concentration at which FDP acts on liver enzyme is remarkably low, about 300-fold lower than is required for a comparable effect in yeast. However, the half-maximal concentration of FDP (0.5 [mu]M) is higher than the concentration reported by Burch (1965) to be present in rat liver (0.02 [mu]M). Since the high affinity of the liver enzyme for FDP is matched by a low intracellular concentration, it is probable that the FDP stimulation constitutes a switching mechanism for liver glycolysis, exerting a positive feed-forward effect as has been suggested for yeast by Hess et al. (1966).

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