Abstract
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.
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