Kinetic trapping of oxygen in cell respiration

Michael Verkhovsky, Joel E. Morgan, Anne Puustinen, Marten Wikstrom

Nature 1996, 380 268-270

Summary: Cell respiration in eukaryotes is catalyzed by the mitochondrial enzyme cytochrome c oxidase. In bacteria there are many variants of this enzyme, all of which have a binuclear haem iron-copper center at which O2 reduction occurs, and a low-spin haem, which serves as the immediate electron donor to this center'. It is essential that the components of the cell respiratory system have a high affinity for oxygen because of the low concentrations of dissolved O2 in the tissues; however, the binding of O2 to the respiratory haem-copper oxidases is very weak. This paradox has been attributed to kinetic trapping during fast reactions of O₂ bound within the enzyme's binuclear haem iron-copper center. Our earlier work indicated that electron transfer from the low spin haem to the oxygen-bound binuclear center may be necessary for such kinetic oxygen trapping. Here we show that a specific decrease of this heme- heme- electron transfer rate in the respiratory haem- copper oxidase from Escherichia cold leads to a corresponding decrease in the enzyme's operational steady state affinity for O₂. This demonstrates directly that fast electron transfer between the heme groups is a key process in achieving the high affinity for oxygen in cell respiration.