Cuprous oxidase activity of yeast Fet3p and human ceruloplasmin: Implication for function

The Fet3 protein in Saccharomyces cerevisiae and mammalian ceruloplasmin are multicopper oxidases (MCO) that are required for iron homeostasis via their catalysis of the ferroxidase reaction, 4Fe²⁺+O₂+4H ⁺→4Fe³⁺+2H₂O. The enzymes may play an essential role in copper homeostasis since they exhibit a strikingly similar kinetic activity towards Cu¹⁺ as substrate. In contrast, laccase, an MCO that exhibits weak activity towards Fe²⁺, exhibits a similarly weak activity towards Cu¹⁺. Kinetic analyses of the Fet3p reaction demonstrate that the ferroxidase and cuprous oxidase activities are due to the same electron transfer site on the enzyme. These two ferroxidases are fully competent kinetically to play a major role in maintaining the cuprous-cupric redox balance in aerobic organisms.