Dissimilar effects of D-mannoheptulose on the phosphorylation of alpha- versus beta-D-glucose by either hexokinase or glucokinase

Abstract

D-mannoheptulose inhibits D-glucose phosphorylation by hexokinase isoenzymes. The present study aims at investigating whether the pattern of such an inhibition differs in the case of alpha- versus beta-D-glucose. The phosphorylation of alpha- and beta-D-[U-14C]glucose was measured over 60-min incubation at 4 degrees C in the presence of bovine heart hexokinase and over 10 min at 24 degrees C in the presence of human liver glucokinase. The relative extent of the inhibitory action of D-mannoheptulose (0.02-10.0 mM) was always less marked with alpha- than beta-D-glucose. In the case of hexokinase, the experiments conducted at the high concentration of the D-glucose anomers (1.0 mM) revealed that D-mannoheptulose, at low concentrations (0.2-0.5 mM), may unexpectedly increase the phosphorylation of alpha-D-glucose. These findings thus document anomeric specificity in terms of the inhibitory action of D-mannoheptulose upon alpha- versus beta-D-glucose phosphorylation by either hexokinase or glucokinase.