Activation of phosphofructokinase from rat tissues by 6-phosphogluconate and fructose 2,6-bisphosphate.
6-Phosphogluconate activates phosphofructokinase from liver, adipose tissue, kidney, and skeletal muscle by decreasing the apparent S0.5 for fructose 6-phosphate without affecting the maximum velocity. The response of phosphofructokinase to 6-phosphogluconate is hyperbolic, with apparent activation constants similar to concentrations of 6-phosphogluconate in tissues. Phosphofructokinase from these tissues is also activated by fructose 2,6-bisphosphate, but the apparent activation constants are much less than the concentrations of fructose 2,6-bisphosphate in tissues. Under most conditions, the effects of 6-phosphogluconate and fructose 2,6-bisphosphate are additive. However, with low concentrations of fructose 6-phosphate there is synergism between the effectors. Whereas fructose 2,6-bisphosphate overcomes the inhibition of phosphofructokinase by high concentrations of ATP, 6-phosphogluconate does not. Thus, the effectors probably act at different sites on the enzyme. The relative effect of 6-phosphogluconate is much greater on phosphofructokinase from the lipogenic tissues, adipose, and liver, than it is on the enzyme from kidney or skeletal muscle. Thus, the influence of 6-phosphogluconate on phosphofructokinase, which could coordinate the disposition of glucose 6-phosphate between the oxidative branch of the hexosemonophosphate pathway and glycolysis, may be important for lipogenesis.
D000227:Adenine Nucleotides / Q000494:pharmacology; D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005635:Fructosediphosphates / Q000494:pharmacology*; D005942:Gluconates / Q000494:pharmacology*; D006598:Hexosediphosphates / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000201:enzymology; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D005635:Fructosediphosphates; D005942:Gluconates; D006598:Hexosediphosphates; C027652:fructose 2,6-diphosphate; D010732:Phosphofructokinase-1; C008884:6-phosphogluconic acid