Structure, oxidant activity, and cardiovascular mechanisms of human ceruloplasmin

Ceruloplasmin is the principal carrier of copper in human plasma. It is an abundant protein that participates in the acute phase reaction to stress, but its physiological function(s) is unknown. An antioxidant activity of ceruloplasmin has been described, but recent evidence suggests that the protein may also exhibit potent pro-oxidant activity and cause oxidative modification of low density lipoprotein (LDL). The pro-oxidant activity is highly dependent on the structure of the protein; removal of a single one of the seven integral copper atoms, or a specific proteolytic cleavage event, completely suppresses LDL oxidation. This newly described pro-oxidant activity may help to explain epidemiological studies indicating that ceruloplasmin is an independent risk factor for cardiovascular disease.