Radical reactions from missing ceruloplasmin
The importance of a ferroxidase as an endogenous antioxidant
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Ceruloplasmin has been believed to transport copper in the blood. However, recent studies of copper metabolism suggest that ceruloplasmin is important for iron, not copper, metabolism. Even though 95% of plasma copper is contained in ceruloplasmin, this copper does not exchange freely with tissue copper and copper does not regulate ceruloplasmin turnover. In fact, copper metabolism is normal in persons who lack ceruloplasmin. Instead, in the rare autosomal recessive condition aceruloplasminemia, the absence of ceruloplasmin profoundly influences the biological activity and distribution of tissue iron.
Ceruloplasmin has enzymatic activity as a plasma ferroxidase and mediates the oxidation of ferrous to ferric iron for insertion into apotransferrin. Transferrin-bound iron proceeds to the bone marrow for the synthesis of hemoglobin and erythropoiesis. Following the degradation of erythrocytes, ceruloplasmin releases iron from the reticuloendothelial system for recycling via transferrin. The sequestration of iron in transferrin has a major antioxidant protective mechanism preventing the direct interaction of iron with tissue components. The importance of this antioxidant property becomes dramatically apparent in the neurologic consequences of aceruloplasminemia. In this issue of Neurology, Miyajima et al. estimate the frequency of ceruloplasmin gene mutations in the Japanese and Tajima et …
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