Metabolic interaction of ethanol and sorbitol in relation to redox state of liver cytosol in hypo-, hyper-, and euthyroid rats

Abstract

Previous investigations have shown that sorbitol delays the rate of ethanol oxidation and conversely that ethanol inhibits the oxidation of sorbitol. These mutual effects have furthermore been found to be enhanced in hypothyroid rats and attenuated in hyperthyroid ones. In the present paper, these effects are demonstrated to be positively correlated with corresponding changes in the redox state of the liver cytosol. Simultaneous oxidation of ethanol and sorbitol elevated the hepatic lactate/pyruvate ratio in vivo from 18 to 71 in hypothyroid rats, from 16 to 53 in euthyroid ones, and from 23 to 33 in hyperthyroid animals. The increases were of the same order when ethanol was metabolized alone. The lactate/pyruvate ratio doubled when sorbitol was given to hypothyroid rats but tended to decrease in hyperthyroid rats. Experiments with liver homogenate indicated no competition between ethanol and sorbitol for the corresponding enzymes, alcohol and sorbitol dehydrogenase. NADH was found to inhibit competitively the rate of oxidation of ethanol and sorbitol in vitro at low levels of NAD +, but calculations showed that the degree of inhibition would probably be of minor importance in vivo. The mechanism by which ethanol and sorbitol inhibit each other's oxidation is suggested to be competition for free NAD +.