Toxicity of 3‐O‐methyl glucose in yeast is due to its phosphorylation by glucokinase

Abstract

3-O-Methyl glucose inhibited the growth of S.cerevisiae on non-fermentable carbon sources only in strains possessing glucokinase. Accumulation of a phosphorylated derivative of 3-O-methyl glucose occurred only in strains carrying glucokinase. Phosphorylation of the sugar in vitro was observed with partially purified preparations of glucokinase but not with equivalent preparations of isoenzymes PI or PI1 of hexokinase. The K,,, value of glucokinase for 3-O-methyl glucose was 5 mM and the I',,,, was N l/100 of that found for glucose. A mutant resistant to 3-O-methyl glucose was isolated from a strain possessing only glucokinase. This mutant had only about 10% of the glucokinase found in the parental strain. 3-O-Methyl glucoseGlucokinase Phosphorylation (Yeast) Hexokinase

Metabolic Stability of 3‐O‐Methyl‐d‐Glucose in Brain and Other Tissues

“…1 B). These results are consistent with recent reports that methylglucose is a substrate, albeit a poor one, for phosphorylation by one of the three yeast isoenzymes of hexokinase (Gatley et al, 1984;Gancedo and Gancedo, 1985;Malaisse-Lagae et al, 1986;Siverio et al, 1986). This isoenzyme is found in commerciaI preparations of yeast hexokinase in variable amounts (Siverio et al, 1986).…”

“…Some recent reports, however, have questioned whether methylglucose is metabolically inert. Methylglucose has been reported to be phosphorylated by yeast and heart hexokinase (Gatley et al, 1984;Gancedo and Gancedo, 1985;Malaise-Lagae et al, 1986;Siverio et al, 1986). Also, on the basis of kinetic analysis of its uptake in brain, measured by positron emission tomography, the speculation was made that [ I 'C]methylglucose was phosphorylated in human brain (Brooks et al, 1986).…”