Rise of Coenzyme A‐Glutathione Mixed Disulfide during Hydroperoxide Metabolism in Perfused Rat Liver

The hepatic metabolism of an externally added hydroperoxide, t-butyl hydroperoxide, results in substantial decreases in CoASH and acetyl-CoA and a concomitant increase in CoA-disulfides. The principal CoA-disulfide which is formed under these conditions was identified as CoASSG, the mixed disulfide of coenzyme A and glutathione; CoASSCoA levels were unchanged. The perturbation in the coenzyme A system was absent when the hydroperoxide was infused into livers from rats maintained on a selenium-deficient diet. In these livers. Se-dependent glutathione peroxidase is lowered to less than 5% of control levels; the observed effects can be attributed to flux through Se-dependent GSH peroxidase.