Reciprocal regulation of fructose 1,6-bisphosphatase and phosphofructokinase by fructose 2,6-bisphosphate in swine kidney.
The effect of fructose 2,6-P2, AMP and substrates on the coordinate inhibition of FBPase and activation of PFK in swine kidney has been examined. Fructose 2,6-P2 inhibits the activity of FBPase and stimulates the activity of PFK in the presence of inhibitory concentrations of ATP. Under similar conditions 2.2 microM fructose 2,6-P2 was required for 50% inhibition of FBPase and 0.04 microM fructose 2,6-P2 restored 50% of the activity of PFK. Fructose 2,6-P2 also enhanced the allosteric activation of PFK by AMP and it increased the extent of inhibition of FBPase by AMP. Fructose 2,6-P2, AMP and fructose 6-P act cooperatively to stimulate the activity of PFK whereas the same latter two effectors and fructose 1,6-P2 inhibit the activity of FBPase. Taken collectively, these results suggest that an increase in the intracellular level of fructose 2,6-P2 during gluconeogenesis could effectively overcome the inhibition of PFK by ATP and simultaneously inactivate FBPase. When the level of fructose 2,6-P2 is low, a glycolytic state would be restored, since under these conditions PFK would be inhibited by ATP and FBPase would be active.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D005636:Fructosephosphates / Q000494:pharmacology / Q000502:physiology*; D007668:Kidney / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine
D005636:Fructosephosphates; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1; D005634:Fructose-Bisphosphate Aldolase