Hormonal control of fructose 2,6-bisphosphate concentration in isolated rat hepatocytes.
The ability of glucagon and of adrenaline to affect the concentration of fructose 2,6-bisphosphate in isolated hepatocytes was re-investigated because of important discrepancies existing in the literature. We were unable to detect a significant difference in the sensitivity of the hepatocytes with regard to the effect of glucagon to initiate the interconversion of phosphorylase, pyruvate kinase, 6-phosphofructo-2-kinase and fructose 2,6-bisphosphatase, and also to cause the disappearance of fructose 2,6-bisphosphate. In contrast, we have observed differences in the time-course of these various changes, since the interconversions of phosphorylase and of pyruvate kinase were at least twice as fast as those of 6-phosphofructo-2-kinase and of fructose 2,6-bisphosphatase. When measured in a cell-free system in the presence of MgATP, the cyclic AMP-dependent interconversion of pyruvate kinase was 5-10-fold more rapid than those of 6-phosphofructo-2-kinase and of fructose 2,6-bisphosphatase. These data indicate that 6-phosphofructo-2-kinase and fructose 2,6-bisphosphatase are relatively poor substrates for cyclic AMP-dependent protein kinase; they also support the hypothesis that the two catalytic activities belong to a single protein. Adrenaline had only a slight effect on the several parameters under investigation, except for the activation of phosphorylase. In the absence of Ca2+ ions from the incubation medium, however, adrenaline had an effect similar to that of glucagon.
D000818:Animals; D002474:Cell-Free System; D000242:Cyclic AMP / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D005635:Fructosediphosphates / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology*; D006598:Hexosediphosphates / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D025481:Phosphofructokinase-2; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005635:Fructosediphosphates; D006598:Hexosediphosphates; C027652:fructose 2,6-diphosphate; D005934:Glucagon; D000242:Cyclic AMP; D006005:Phosphorylases; D017853:Phosphotransferases (Alcohol Group Acceptor); D025481:Phosphofructokinase-2; D011770:Pyruvate Kinase; D010744:Phosphoric Monoester Hydrolases; D004837:Epinephrine