Relationship of Cardiolipin to Cytochrome c Oxidase Kinetics as Probed by Adriamycin
The interaction of cytochrome c oxidase with mitochondrial phospholipids recently has received a great deal of scrutiny (Dennis, 1986). Much of this work has been focused specifically on the functional relationship between cardiolipin and oxidase, however, this dependence is now being questioned (Watts et al., 1978; Powell and Abramovitch, 1985). Utilizing the observation that the anthracycline antibiotic, adriamycin, forms undissociable complexes with cardiolipin, investigations have been carried out using this drug to illustrate the involvement of this acidic phospholipid in various mitochondrial membrane-related processes (Goormaghtigh and Ruysschaert, 1984). Adriamycin first recognized for its antineoplastic activity (Gianni et al., 1983), has been shown to have cellular toxicological effects, causing cardiac toxicity (Demant and Wassermann, 1985) and impaired mitochondrial function (Praet et al., 1984). Ruysschaert and his co-workers (1982) demonstrated that this drug blocked mitochondrial electron flow by inactivating cytochrome c oxidase. Their data suggested that adriamycin sequestered closely associated cardiolipin molecules from the enzyme by forming an adriamycin-cardiolipin complex and thereby inhibiting oxidase activity.
KeywordsOxidase Activity Late Exponential Phase Anthracycline Antibiotic Mitochondrial Phospholipid Biphasic Kinetic
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