Anomeric specificity of the stimulatory effect of D-glucose on D-fructose phosphorylation by human liver glucokinase.
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 degrees C, alpha-D-glucose (5.6 mm), but not beta-D-glucose (also 5.6 mm), augmented significantly the conversion of D-[U-(14)C]fructose (5.0 mm) to acidic radioactive metabolites. Likewise, in islets prelabeled with (45)Ca and perifused at 37 degrees C, D-fructose (20.0 mm) augmented (45)Ca efflux and provoked a biphasic stimulation of insulin release from islets exposed to alpha-D-glucose (5.6 mm), while inhibiting (45)Ca 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.
Jijakli
Hassan
H
Laboratory of Experimental Medicine, Brussels Free University, B-1070 Brussels, Belgium.
Courtois
Philippe
P
Zhang
Hai-Xia
HX
Sener
Abdullah
A
Malaisse
Willy J
WJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000737:chemistry / Q000378:metabolism*; D005941:Glucokinase / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D010766:Phosphorylation; D051381:Rats
D005632:Fructose; D005941:Glucokinase; D005947:Glucose