INVITRO INACTIVATION OF LACTATE-DEHYDROGENASE BY ORGANOCHLORINE INSECTICIDES

The inactivation of beef, rabbit, and salmon isozymes of lactate dehydrogenase by dieldrin, Kepone, mirex, o,p′-DDT, and p,p′-DDT was carefully investigated. Enzyme inactivation was only observed when the polychlorinated compounds were added in excess of their respective solubility limits. Partial solubilization of the organochlorine insecticides by the cosolvent, ethanol, or the surfactant Triton X-100 greatly decreases or totally eliminates this inactivation. The addition of bovine serum albumin to the reaction mixtures also diminishes the inactivating effect. Protein analysis of enzyme solutions to which stock solutions of the organochlorine insecticides were added show that, as precipitation of the compounds takes place, protein is physically removed from solution. The kinetic behavior of lactate dehydrogenase partially inhibited by oxamate or bromphenol blue differs fundamentally from that of the enzyme partially inactivated by the insecticides. Taken together, the results of the present work indicate that enzyme inactivation is not due to chemical inhibition, but rather to coprecipitation in which the enzyme is physically occluded by the precipitating organochlorine compounds. It is also shown that the muscle isozymes of lactate dehydrogenase are considerably more susceptible toward copreciptiation than the corresponding heart isozymes. The biochemical significance of the observed differential coprecipitation of the isozymes of lactate dehydrogenase by organochlorine insecticides is discussed in light of our experimental observations. © 1979.