Methyl hydroperoxy-epoxy-octadecenoate as an autoxidation product of methyl linoleate: a new inhibitor-uncoupler of mitochondrial respiration.
A new peroxide compound (ML-X) was isolated from an autoxidation product of methyl linoleate and was determined as methyl 9-hydroperoxy-12, 13-epoxy-10-octadecenoate. This compound inhibited state 3 respiration of rat heart- and liver mitochondria when glutamate and malate were used as substrates, but not when the substrate was succinate. State 4 respiration of mitochondria was not affected when glutamate-malate was used as the substrate, but it was stimulated when the substrate was succinate. ML-X inhibited oxidative phosphorylation of the mitochondria and abolished the membrane potential formed by respiration or by added ATP. NADH oxidase activity of submitochondrial particles was inhibited by ML-X but succinate oxidase activity was not inhibited. NADH-acceptor reductase activities of submitochondrial particles were inhibited by ML-X to the same extents as by rotenone. These findings show that ML-X has dual effects on mitochondrial respiration as (1) an inhibitor of NADH dehydrogenase complex and (2) an uncoupler. Neither methyl linoleate monohydroperoxide nor methyl epoxy stearate has such effects. ML-X is a new type of inhibitor-uncoupler of mitochondrial respiration in which hydroperoxy- and epoxy groups co-operate.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004852:Epoxy Compounds / Q000302:isolation & purification* / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000302:isolation & purification*; D066298:In Vitro Techniques; D008041:Linoleic Acids / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D014475:Uncoupling Agents / Q000302:isolation & purification*
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D008041:Linoleic Acids; D014475:Uncoupling Agents; C005575:methyl linoleate; C036362:methyl 9-hydroperoxy-12,13-epoxy-10-octadecenoic acid; D009245:NADH Dehydrogenase