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Dissociated effects of 2-deoxy-D-glucose on D-[2-3H]glucose and D-[5-3H]glucose conversion into 3HOH in rat
B Manuel y Keenoy1, D Zähner, W J Malaisse
1Laboratoire de Médecine Expérimentale, Faculté de Médecine Erasme, Université Libre de Bruxelles, Belgium.
Abstract:
When rat erythrocytes were preincubated with 2-deoxy-D-glucose, the generation of both 3H-labelled acidic metabolites and 3HOH from D-[5-3H]glucose, the total production of L-lactate, and the generation of 14CO2, 14C-labelled acidic metabolites and 14C-labelled lactate from D-[1-14C]glucose or D-[U-14C]glucose were all lower than in erythrocytes preincubated in the absence of a hexose or in the presence of 3-O-methyl-D-glucose. However, preincubation with 2-deoxy-D-glucose failed to decrease the generation of 3H-labelled acidic metabolites and L-[3-3H]lactate from D-[2-3H]glucose, while decreasing the production of 3HOH more severely from D-[2-3H]glucose than from D-[5-3H]glucose. This may be attributable not solely to inhibition of D-glucose phosphorylation by 2-deoxy-D-glucose and 2-deoxy-D-glucose 6-phosphate, but also to inhibition by 2-deoxy-D-glucose 6-phosphate of hexose 6-phosphate interconversion in the reaction catalysed by phosphoglucoisomerase, as also observed with the purified enzyme. The generation of 3HOH from D-[2-3H]glucose should therefore be considered as a tool to assess the efficiency of interconversion of hexose 6-phosphates in the reaction catalysed by phosphoglucoisomerase, rather than to estimate D-glucose phosphorylation rate.
