Hexose metabolism in pancreatic islets: enzyme-to-enzyme tunnelling of hexose 6-phosphates.
The fate of unlabelled D-glucose and D-[2-3H]glucose in pancreatic islets was simulated taking into account experimental values for glycolytic flux, intracellular concentration of D-glucose 6-phosphate and phosphoglucoisomerase activity. The model, which also takes into account the isotopic discrimination in velocity and intramolecular transfer of tritium between D-[2-3H]glucose 6-phosphate and D-[1-3H]fructose 6-phosphate in the reaction catalyzed by phosphoglucoisomerase, revealed that the predicted generation of 3HOH from D-[2-3H]glucose was much higher than the true experimental value. Such a discrepancy is reinforced by the consideration that the generation of 3HOH from D-[2-3H]glucose in islet cells is not solely attributable to the phosphoglucoisomerase-catalyzed detritiation of hexose 6-phosphates metabolized in the glycolytic pathway. In order to reconcile experimental and theoretical values for 3HOH production, it was found necessary to postulate enzyme-to-enzyme tunnelling of hexose 6-phosphates in the hexokinase/phosphoglucoisomerase/phosphofructokinase sequence. It is proposed that such a tunnelling may favour the anomeric specificity of D-glucose metabolism in islet cells, by restricting the anomerization of hexose 6-phosphates.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Bodur
H
H
D000818:Animals; D005947:Glucose / Q000378:metabolism; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism; D006600:Hexosephosphates / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D009097:Multienzyme Complexes; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D014867:Water / Q000378:metabolism
D006600:Hexosephosphates; D006601:Hexoses; D009097:Multienzyme Complexes; D014867:Water; D006593:Hexokinase; D010732:Phosphofructokinase-1; D005956:Glucose-6-Phosphate Isomerase; D005947:Glucose