Ceruloplasmin: Structure and function of an essential ferroxidase

Abstract

This chapter discusses the structure and function of an essential ferroxidase—ceruloplasmin. Serum ceruloplasmin is secreted by the liver and is very abundant being present at the levels of 300–450 μg/ml. Only a few other proteins, such as albumin and transferring, are found at higher concentrations in the serum. This glycoprotein of approximately 135 kDa carries 90–95% of the copper in the serum. Ceruloplasmin has a long evolutionary history and is found in mammals, birds, and reptiles. Several functions are attributed to ceruloplasmin based on both in vitro and in vivo data, including roles in copper transport, antioxidant defense, and iron metabolism. The absence of ceruloplasmin leads to a striking degree of iron deposition in various tissues and to severe neuropathological changes. The chapter discusses the structure–function relationship of ceruloplasmin, compares its structure with those of other blue copper oxidases—the phenotype resulting from mutations in the ceruloplasmin gene—and examines the recent evidence for different forms of ceruloplasmin in mammals. The important role of ceruloplasmin in mobilizing iron out of the brain and its potential role in neurodegenerative disease is also focused in the chapter.