Superoxide Radical Release into the Cytoplasm of Heart Cells by an NADH-Driven Oxygen Activator
It is now unequivocally accepted, mainly on the basis of indirect evidence1–4 that heart mitochondria (RHM) release small amounts of superoxide radicals as a physiological byproduct of respiration. The existence of this process indicates not only that the oxygen radical generator is able to establish an adequate redox couple with molecular oxygen but also its interaction with the physiological electron acceptor exhibits kinetic restraints, causing electron deviation from the normal pathway to oxygen at a nonphysiological site of the respiratory chain. In isolated, normally functioning mitochondria, the latter condition was found to be closely related to energy coupling since superoxide radical formation was only observed under conditions in which, due to a lack of ADP, mitochondria were hindered from ATP-synthesis (= state 4 conditions of respiration). Although such conditions are not likely to exist in highly active energy-consuming organs, there is convincing evidence that O 2 - formation occurs in the living heart2,3.
KeywordsHeart Mitochondrion Oxygen Radical Generator Cytosolic NADH Superoxide Radical Formation External NADH
Unable to display preview. Download preview PDF.
- 4.H. Nohl, The biochemical mechanism of the formation of reactive oxygen species in heart mitochondria, in: “Advances in Studies on Heart Metabolism”, B. M. Caldarera and P. Harris, eds, CLUEB, Bologna (1982).Google Scholar
- 6.H. Nohl, Identification of the site of adriamycin activation in the heart cell. Biochem. Pharmacol. in press (1988).Google Scholar
- 8.E. Bernt and H.ü. Bergmeyer, Anorganische Peroxide, in: “Methoden der enzyroatischen Analyse”, H.U. Bergmeyer, ed, Verlag Chemie, Weinheim (1974).Google Scholar