Copper—A Modern Bioelement

From the analysis of the evolution of copper-containing enzymes, it emerges that copper is a modern bioelement. It was not used as an enzyme cofactor before the advent of oxygen evolution. In the anoxic world, copper in the biosphere was in its reduced, Cu+ state, which formed insoluble copper sulfide, promoted by the abundance of hydrogen sulfide in the atmosphere. Once the world became oxic, Cu+ was oxidized to Cu2+, which is readily soluble in the aqueous phase. The ensuing bioavailability of copper led to the evolution of cuproenzymes and copper-responsive regulators of gene expression. Indeed, all known copper-containing enzymes catalyze redox reactions involving oxygen in one form or another. Copper detoxification systems, on the other hand, have an earlier, independent evolutionary origin. The redox-active nature of copper of course makes it an ideal cofactor for redox enzymes, but also pose special experimental problems, which are discussed.