Inhibition of human ceruloplasmin (ferroxidase) by cadmium

Abstract

Ceruloplasmin (Cp) is a human plasma protein with multiple physiological functions including ferroxidase and oxidase activities. Deficiency or inhibition of the enzyme may lead to some abnormalities, including iron deposition in several tissues and causes various pathological conditions in the body. Direct interaction of cadmium (Cd), a widespread, highly toxic environmental pollutant, with human Cp leads to reversible inhibition of the enzyme. Therefore, investigation of kinetic parameters of Cp in the presence of Cd will lead to a better understanding of mechanism by which Cd inhibit Cp activity. In the present study, Cd inhibited Cp in vitro progressively up to a concentration of 2 mM where about 75% of the enzyme activity was lost 10 min after addition of Cd. An inhibitory constant (ki) of about 1.1 mM was calculated from the slope replot. Fluoroscopic study also was carried out on the native and Cd-inhibited enzyme. Maximum emission spectrum of the inhibited enzyme showed an increased level of about 62% with regard to the native enzyme. Cd-induced enzyme inhibition was prevented by sulfhydryl compounds such as glutathione (1.2, 12 mM), and b-mercaptoethanol (12 mM). The data suggest that a conformational change in the native enzyme due to Cd binding caused enzyme inactivation and sulfhydryl groups on the enzyme probably are involved in inhibition by Cd.