Glucose-induced positive cooperativity of fructose phosphorylation by human B-cell glucokinase.
Human B-cell glucokinase displays sigmoidal kinetics towards D-glucose or D-mannose, but fails to do so towards D-fructose. Yet, D-glucose, D-mannose and 2-deoxy-D-glucose confer to the enzyme positive cooperativity towards D-fructose. For instance, in the presence of 5 mM D-[U-14C]fructose, its rate of phosphorylation is increased to 214.3 +/- 11.0%, 134.0 +/- 4.3% and 116.5 +/- 3.0% of paired control value by D-glucose, D-mannose and 2-deoxy-D-glucose (each 6 mM), respectively. D-glucose and, to a lesser extent, D-mannose also display reciprocal kinetic cooperativity. D-fructose, however, fails to affect D-glucose or D-mannose phosphorylation under conditions in which positive cooperativity is otherwise observed. These findings are relevant to the reciprocal effects of distinct hexoses upon their phosphorylation by B-cell glucokinase and, as such, to the metabolic and functional response evoked in pancreatic islet B-cells by these sugars, when tested either separately or in combination.
Scruel
O
O
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Sener
A
A
Malaisse
W J
WJ
D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005632:Fructose / Q000378:metabolism*; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008358:Mannose / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects
D005632:Fructose; D005941:Glucokinase; D005947:Glucose; D008358:Mannose