Ceruloplasmin has a distinct active site for the catalyzing glutathione-dependent reduction of alkyl hydroperoxide

Ceruloplasmin, a blue multi-copper alpha(2)-glycoprotein found in the plasm a of all vertebrates, is capable of oxidizing aromatic amines and ferrous i ron. Here, we report that human ceruloplasmin exhibits an alkyl hydroperoxi de peroxidase activity, which is independent of the oxidase activity. The s ite-specific modification of the sulfhydryl of cysteine at position 699 in ceruloplasmin completely abolished the antioxidant activity, suggesting tha t ceruloplasmin is a peroxidase with a cysteinyl thiol as a functional nucl eophile. The crystal structure of human ceruloplasmin reveals that the doma in containing Cys-699 is apart from the multi-copper complex domains. Taken together, these data suggest that ceruloplasmin has a distinct active site for a glutathione-linked peroxidase activity apart from the copper complex site exerting ferroxidase activity.