Detrimental effects of methyl hydroperoxy-epoxy-octadecenoate on mitochondrial respiration: detoxication by rat liver mitochondria.
Methyl hydroperoxy-epoxy-octadecenoate (ML-X) inhibited state 3 respiration of rat heart and liver mitochondria with glutamate and malate as substrates. It also inhibited the NADH oxidase and NADH-ubiquinone-1 reductase activities of rat heart and liver submitochondrial particles (SMP). In liver mitochondria and SMP, these inhibitory effects of ML-X were transient, whereas in heart mitochondria and SMP, recovery of the respiratory activities did not occur. Results from high pressure liquid chromatography and 13C-NMR studies indicated that ML-X was converted to hydroperoxy-epoxy-octadecenoic acid (L-X) by incubation with liver mitochondria or SMP but not with heart mitochondria. Purified L-X apparently inhibited state 3 respiration of heart and liver mitochondria with glutamate and malate as substrates, but the amount required for 50% inhibition was 2-3 times larger than that of ML-X. Heart mitochondria adsorbed 36% of the added ML-X, while only 10% of the added L-X was adsorbed. These findings suggest that the recovery of the ML-X-inhibited respiratory activities of liver mitochondria and SMP occurs by conversion of ML-X to L-X, which is only weakly adsorbable on the mitochondrial membrane.
D000327:Adsorption; D000818:Animals; D004852:Epoxy Compounds / Q000378:metabolism / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone); D010101:Oxygen Consumption / Q000187:drug effects*; D011808:Quinone Reductases / Q000378:metabolism; D051381:Rats
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; C036362:methyl 9-hydroperoxy-12,13-epoxy-10-octadecenoic acid; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases