The mechanism of red-cell hexokinase inhibition induced by oxidation of intracellular glutathione and its relation to drug sensitivity

Abstract

Reduced glutathione at 1 mM concentration is able to mantain rabbit red blood cell hexokinase (EC 2.7.1.1) in the reduced stated with fully catalytic activity. At higher concentrations a marked inhibition is observed. In contrast, oxidized glutathione is a strong inhibitor of reduced erythrocyte hexokinase at all the concentrations studied.Inactivation experiments show that some sulfhydryl groups reacting with oxidized glutathione are responsible for the enzyme inactivations. These findings suggest a cellular inter-relationship between redox and energetic metabolism coupled through glutathione at the hexokinase level.