Arachidonic acid interaction with the mitochondrial electron transport chain promotes reactive oxygen species generation.
A study has been carried out on the interaction of arachidonic acid and other long chain free fatty acids with bovine heart mitochondria. It is shown that arachidonic acid causes an uncoupling effect under state 4 respiration of intact mitochondria as well as a marked inhibition of uncoupled respiration. While, under our conditions, the uncoupling effect is independent of the fatty acid species considered, the inhibition is stronger for unsaturated acids. Experiments carried out with mitochondrial particles indicated that the arachidonic acid dependent decrease of the respiratory activity is caused by a selective inhibition of Complex I and III. It is also shown that arachidonic acid causes a remarkable increase of hydrogen peroxide production when added to mitochondria respiring with either pyruvate+malate or succinate as substrate. The production of reactive oxygen species (ROS) at the coupling site II was almost double than that at site I. The results obtained are discussed with regard to the impairment of the mitochondrial respiratory activity as occurring during the heart ischemia/reperfusion process.
Cocco
T
T
Institute of Medical Biochemistry and Chemistry, University of Bari, Italy.
Di Paola
M
M
Papa
S
S
Lorusso
M
M
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D004579:Electron Transport; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism*
D009097:Multienzyme Complexes; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D019308:Palmitic Acid; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III