Abstract
Cytochrome c oxidase is the terminal oxidase in cellular respiration. This membrane protein accepts electrons from ferrocytochrome c in the periplasmic space of the mitochondrion, one electron at a time, and transfers the reducing equivalents to the binuclear heme-iron copper site (the so-called Fea3, CuB site), where dioxygen binds and the O·O bond is subsequently cleaved (1). In this manner, the binuclear center is activated by the dioxygen, and the heme iron is oxidized by two oxidizing equivalents to form Fea3–oxyferryl, namely, Fea34+ = O2−, and the CuB site by two oxidizing equivalents to form the CuB2+–OH−/tyrosyl radical species (2). Subsequent inputs of addi-tional reducing equivalents from reduced cytochrome c to the low-potential CuA and Fea centers and the transfers of these electrons to the activated binuclear center are linked to proton pumping (3).