Symposium: Prooxidant Effects of Antioxidant Vitamins Vitamin C-Driven Free Radical Generation from Iron1'2

Circulating free iron is lethal. Humans have two circulating iron binding proteins to soak up free iron to prevent it from generating toxic quantities of free radicals. These proteins are transferrin, a highaffinity, low-capacity protein (2 atoms of iron per mole cule of transferrin) for which there are receptors on the surface of every iron-requiring cell; and ferritin, a lower-affinity, high-capacity protein (maximum of 4500 atoms of iron per molecule of ferritin) for which there are receptors only on the surface of iron-storage cells such as RE (reticulo-endothelial) cells. Iron is trapped inside the ferritin protein shell as harmless Fe3. When there is a high serum level of reduced ascorbic acid, it drives through the pores of the ferritin protein shell to the inside surface, where it converts the Fe, to catalytic Fe2, which then leaks out of the pores of the ferritin protein shell and generates billions of free radicals. In normal individuals, per milliliter of serum, there are approximately 300,000 molecules of transferrin per molecule of ferritin. Ferritin protein is an acute phase reactant that sharply rises in the pres ence of inflammation of any kind, whereas transferrin is a reverse acute phase reactant that falls in the pres ence of inflammation of any kind. J. Nutr. 126: 1213S-1220S, 1996.