Pancreatic islet discrimination of hexose anomers. I. Steady-state computer simulation.
Pancreatic islets detect glucose level by phosphorylating it and converting the glycolytic rate to a signal to secrete insulin. Insulin secretion is greater from the alpha- than from the beta-anomer when the D-glucose level is below 22 mM. D-mannose behaves similarly but at nearly twofold higher concentrations. Two explanations have been proposed: 1) glucokinase, which has the same anomeric preference, is the principal hexose phosphorylating enzyme and limits glycolytic rate. 2) Phosphofructokinase limits glycolysis and hexokinase is the principal enzyme phosphorylating hexose; hexosediphosphate activators of phosphofructokinase are more readily synthesized from alpha-anomers of hexose phosphates. We have simulated both alternatives with a detailed anomerically specific model of the hexose-metabolizing glycolytic enzymes. The pathway preference for alpha-anomer of both hexoses was adequately reproduced with anomerically active limiting glucokinase. The other mechanism did not reproduce the observed pathway preference.
Achs
M J
MJ
Department of Computer Science, University of Pennsylvania, Philadelphia 19104.
Garfinkel
D
D
D000818:Animals; D003198:Computer Simulation; D005947:Glucose / Q000378:metabolism / Q000502:physiology*; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism; D006601:Hexoses / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007536:Isomerism; D007700:Kinetics; D008954:Models, Biological; D010732:Phosphofructokinase-1 / Q000378:metabolism
D006601:Hexoses; D007328:Insulin; D006593:Hexokinase; D010732:Phosphofructokinase-1; D005947:Glucose