The inactivation of isocitrate dehydrogenase by a lipid peroxide

The isocitrate dehydrogenases of rat liver were found extremely sensitive to inacvation by linoleic acid hydroperoxide. Lipid peroxide was much more effective than other peroxides and sulfhydryl reagents tested. Dehydrogenase activity of crude subcellular fractions was more sensitive than the activity of the purified enzyme. The inactivation was not catalyzed by heme compounds. Loss of enzyme activity was accompanied by a decrease in the SH content of the enzyme. Inactivation was facilitated at elevated pH. The binding of p -chloromercuribenzoate to the enzyme protected against peroxide. The SH groups of isocitrate dehydrogenase were more reactive with linoleic acid hydroperoxide than any SH groups so far tested. It was concluded that inactivation is probably due to SH destruction and that modification of an essential methionine residue is unlikely to be a contributory factor. The unique features of the inactivation of isocitrate dehydrogenase by lipid peroxide are discussed.