Inhibition of phosphofructokinase by fructose 1,6-diphosphatase in mammalian systems: Protein-protein interaction or fructose 1,6-diphosphate trapping?

Abstract

The aim of the investigation was to discriminate between a direct inhibitory effect of fructose 1,6-diphosphatase (FDPase) (EC 3.1.3.11) on phosphofructokinase (PFK) (EC 2.7.1.11) and an inhibition of the PFK-catalyzed reaction by removal of FDP. The following results strongly support the second hypothesis, (i) Inhibition of PFK by FDPase directly follows the decrease of the actual concentrations of FDPase. (ii) FDPase has no inhibitory effect as long as the concentration of FDP is kept above 2 μ m. (iii) FDPase has no inhibitory effect when PFK activation is achieved by glucose 1,6-diphosphate, which is not split by FDPase. (iv) FDPase has an inhibitory effect when the activation is achieved by sedoheptulose 1,7-diphosphate, which is split by FDPase. (v) High concentrations of aldolase inhibited the PFK-catalyzed reaction. The degree of inhibition showed a similar correlation with the level of FDP in the assay system when FDPase instead of aldolase was used, (vi) FDP-equilibrated PFK, but not glucose 1,6-diphosphate-equilibrated PFK, is inactivated by FDPase. (vii) Muscle and liver PFK react in the same way with either muscle or liver FDPase.