Enzyme inactivation and inhibition by gossypol

Three lactate dehydrogenase isozymes and malate dehydrogenase purified from mouse tissues were inactivated with time by low concentration of gossypol. The degree of enzyme inactivation is both gossypol- and enzyme-concentration-dependent. Under the same experimental conditions, lactate dehydrogenase-X and lactate dehydrogenase-5 were inactivated faster than lactate dehydrogenase-1. NADH was shown to partially protect the enzymes against inactivation by gossypol. The results of this study suggest that the enzymes are inactivated by the minor components in gossypol preparations. Isozymes of glutathione S-transferases were reversibly inhibited by gossypol. The inhibition of transferases by gossypol was shown to be competitive with respect to the 1-chloro-2,4-dinitrobenzene. It is proposed that the male antifertility effect of gossypol may be related to the selective inactivation of sperm-specific lactate dehydrogenase-X.