Effect of Hydrophobic Molecules on Mitochondria and Mitochondrial Proteins.
Final rept. 1 Aug 1989-31 Jan 1990
OKLAHOMA STATE UNIV STILLWATER DEPT OF MICROBIOLOGY
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Inhibition of electron transfer steps in mitochondrial respiration was studied. The effects of polyaromatic hydrocarbons such as benzene or acenaphthene, the local anesthetic dibucaine, and the cardiac beta-blocker propranolol on CO recombination to cytochrome oxidase following flash photolysis have been determined. The drugs and benzeneacenaphthene slow the rate of CO recombination. The energies of activation of CO recombination are altered. The most significant finding is the induction of bi-phasic kinetics by the drugs or solvents such as alcohol and the pH-dependence of those kinetics. A mechanism for the inhibition of CO recombination and the pH dependency of the kinetic parameters in both the control and drug-treated samples is discussed. The effects of local anesthetics dibucaine, tetracaine, and procaine and the beta blocker propranolol on ubiquinol-cytochrome c reductase activities has determined that dibucaine and propranolol inhibit electron transfer between cytochrome c1 and c at all pH values the drugs inhibit electron transfer between cytochrome b562 and cytochrome c1 at pH values below 6.5. This study elaborates on the pH-dependency of the inhibition of electron transport reactions since proteins exposed on the cytoplasmic face are to acidic conditions while those on matrix face are exposed to alkaline conditions during phosphorylation and proton translocation. Understanding of the pH-effects of inhibitions by hydrophobic compounds is essential to understand their deleterious effects.
- Anatomy and Physiology