Redox-active metal ions are present in the cell in their free, uncomplexed state only in extremely low concentrations. They are instead sequestered by metal-ion storage and transport proteins, such as ferritin and transferrin for iron (see Chapter 1) and ceruloplasmin for copper. This arrangement prevents such metal ions from catalyzing deleterious oxidative reactions, but makes them available for incorporation into metalloenzymes as they are needed.
In vitro experiments have shown quite clearly that redox-active metal ions such as Fe 2 + /3+ or Cu +/2+ are extremely good catalysts for oxidation of sulfhydryl groups by O2 (Reaction 5.27).
In addition, in the reducing environment of the cell, redox-active metal ions catalyze a very efficient one-electron reduction of hydrogen peroxide to produce hydroxyl radical, one of the most potent and reactive oxidants known (Reactions 5.28 to 5.30).
Binding those metal ions in a metalloprotein usually prevents them from entering into these types of reactions. For example, transferrin, the iron-transport enzyme in serum, is normally only 30 percent saturated with iron. Under conditions of increasing iron overload, the empty iron-binding sites on transferrin are observed to fill, and symptoms of iron poisoning are not observed in vivo until after transferrin has been totally saturated with iron. 32 Ceruloplasmin and metallothionein may playa similar role in preventing copper toxicity. 6 It is very likely that both iron and copper toxicity are largely due to catalysis of oxidation reactions by those metal ions.
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