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Originally published In Press as doi:10.1074/jbc.M206730200 on November 19, 2002

J. Biol. Chem., Vol. 278, Issue 7, 4531-4535, February 14, 2003
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Anomeric Specificity of the Stimulatory Effect of D-Glucose on D-Fructose Phosphorylation by Human Liver Glucokinase*

Hassan Jijakli, Philippe Courtois, Hai-Xia Zhang, Abdullah Sener, and Willy J. MalaisseDagger

From the Laboratory of Experimental Medicine, Brussels Free University, B-1070 Brussels, Belgium

D-Glucose was recently reported to stimulate D-fructose phosphorylation by human B-cell glucokinase. The present study aims at investigating the anomeric specificity of such a positive cooperativity. The alpha -anomer of D-glucose was found to increase much more markedly than beta -D-glucose the phosphorylation of D-fructose by human liver glucokinase. Such an anomeric preference diminished at high concentrations of the D-glucose anomers, i.e. when the effect of the aldohexose upon D-fructose phosphorylation became progressively less marked. A comparison between the effects of the two anomers of D-glucose and those of equilibrated D-glucose upon D-fructose phosphorylation by human liver glucokinase indicated that the results obtained with the equilibrated aldohexose were not significantly different from those expected from the combined effects of each anomers of D-glucose. In isolated rat islets incubated for 60 min at 4 °C, alpha -D-glucose (5.6 mM), but not beta -D-glucose (also 5.6 mM), augmented significantly the conversion of D-[U-14C]fructose (5.0 mM) to acidic radioactive metabolites. Likewise, in islets prelabeled with 45Ca and perifused at 37 °C, D-fructose (20.0 mM) augmented 45Ca efflux and provoked a biphasic stimulation of insulin release from islets exposed to alpha -D-glucose (5.6 mM), while inhibiting 45Ca efflux and causing only a sluggish and modest increase in insulin output from islets exposed to beta -D-glucose (also 5.6 mM). The enhancing action of D-glucose upon D-fructose phosphorylation by glucokinase thus displays an obvious anomeric preference for alpha -D-glucose, and such an anomeric specificity remains operative in intact pancreatic islets.


* This work was supported by Grants 3.4567.97 and 3.4517.02 from the Belgian Foundation for Scientific Medical Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Laboratory of Experimental Medicine, Brussels Free University, 808 Route de Lennik, B-1070 Brussels, Belgium. Tel.: 32-2-5556237; Fax: 32-2-5556239; E-mail: malaisse@ulb.ac.be.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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