Comparison of the inhibitory effects of mercuric chloride on cytosolic and mitochondrial hexokinase activities in rat brain, kidney and spleen.

Hg2+ (10-20 microM), at concentrations comparable to mercury levels reportedly occurring in mercury neurotoxicity (Minamata disease), effectively inhibited both cytosolic (IC50 for Hg2+ = 4.1 microM) and mitochondrial (IC50 for Hg2+ = 1.4 microM) rat brain hexokinases. Kidney (IC50 for Hg2+ approximately equal to 3 microM) and spleen hexokinases were less susceptible to inhibition by Hg2+. IC50 values for Hg2+ in inhibiting cytosolic and mitochondrial spleen hexokinases were 8.9 and 3.1 microM, respectively. In both brain and spleen, mitochondrial hexokinases were more susceptible to inhibition by Hg2+ than cytosolic forms, suggesting that the microenvironment of the mitochondrial membranes may exert some modulatory effects on the properties of hexokinases. These results also suggest that inhibition of glucose utilization may be an important mechanism of tissue damage in mercury poisoning.