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000007755 0247_ $$2pmid$$apmid:19627079
000007755 0247_ $$2DOI$$a10.1021/ja904343c
000007755 0247_ $$2WOS$$aWOS:000269379200009
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000007755 041__ $$aeng
000007755 082__ $$a540
000007755 084__ $$2WoS$$aChemistry, Multidisciplinary
000007755 1001_ $$0P:(DE-HGF)0$$aBelikova, N.A.$$b0
000007755 245__ $$aHeterolytic reduction of fatty acid hydroperoxides by cytochrome c/cardiolipin complexes: antioxidant function in mitochondria
000007755 260__ $$aWashington, DC$$bAmerican Chemical Society$$c2009
000007755 300__ $$a11288 - 11289
000007755 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000007755 440_0 $$08502$$aJournal of the American Chemical Society$$v131$$x0002-7863$$y32
000007755 500__ $$aThis work was supported by grants from the NIH (U19-AI068021, HL70755, R03TW007320, 2RO1LM007994-05), the NSF (CC0449117), the PittGrid, and la Junta de Extremadura, Orden 2008050288 (A.K.S.A.).
000007755 520__ $$aCytochrome c (cyt c), a mitochondrial intermembrane electron shuttle between complexes III and IV, can, upon binding with an anionic phospholipid, cardiolipin (CL), act as a peroxidase that catalyzes cardiolipin oxidation. H(2)O(2) was considered as a source of oxidative equivalents for this reaction, which is essential for programmed cell death. Here we report that peroxidase cyt c/CL complexes can utilize free fatty acid hydroperoxides (FFA-OOH) at exceptionally high rates that are approximately 3 orders of magnitude higher than for H(2)O(2). Similarly, peroxidase activity of murine liver mitochondria was high with FFA-OOH. Using EPR spin trapping and LC-MS techniques, we have demonstrated that cyt c/CL complexes split FFA-OOH predominantly via a heterolytic mechanism, yielding hydroxy-fatty acids, whereas H(2)O(2) (and tert-butyl hydroperoxide, t-BuOOH) undergo homolytic cleavage. Computer simulations have revealed that Arg(38) and His(33) are important for the heterolytic mechanism at potential FFA-OOH binding sites of cyt c (but not for H(2)O(2) or t-BuOOH). Regulation of FFA-OOH metabolism may be an important function of cyt c that is associated with elimination of toxic FFA-OOH and synthesis of physiologically active hydroxy-fatty acids in mitochondria.
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000007755 588__ $$aDataset connected to Web of Science, Pubmed
000007755 650_2 $$2MeSH$$aAnimals
000007755 650_2 $$2MeSH$$aAntioxidants: metabolism
000007755 650_2 $$2MeSH$$aArmoracia: enzymology
000007755 650_2 $$2MeSH$$aCardiolipins: metabolism
000007755 650_2 $$2MeSH$$aCytochromes c: metabolism
000007755 650_2 $$2MeSH$$aFatty Acids: metabolism
000007755 650_2 $$2MeSH$$aHydrogen Peroxide: metabolism
000007755 650_2 $$2MeSH$$aMitochondria, Liver: enzymology
000007755 650_2 $$2MeSH$$aModels, Molecular
000007755 650_2 $$2MeSH$$aMurinae
000007755 650_2 $$2MeSH$$aOxidation-Reduction
000007755 650_2 $$2MeSH$$aProtein Binding
000007755 650_7 $$00$$2NLM Chemicals$$aAntioxidants
000007755 650_7 $$00$$2NLM Chemicals$$aCardiolipins
000007755 650_7 $$00$$2NLM Chemicals$$aFatty Acids
000007755 650_7 $$07722-84-1$$2NLM Chemicals$$aHydrogen Peroxide
000007755 650_7 $$09007-43-6$$2NLM Chemicals$$aCytochromes c
000007755 650_7 $$2WoSType$$aJ
000007755 7001_ $$0P:(DE-HGF)0$$aTyurina, Y.Y.$$b1
000007755 7001_ $$0P:(DE-HGF)0$$aBorisenko, G.$$b2
000007755 7001_ $$0P:(DE-HGF)0$$aTyurin, V.$$b3
000007755 7001_ $$0P:(DE-HGF)0$$aSamhan Arias, A.K.$$b4
000007755 7001_ $$0P:(DE-HGF)0$$aYanamala, N.$$b5
000007755 7001_ $$0P:(DE-HGF)0$$aFurtmüller, P.G.$$b6
000007755 7001_ $$0P:(DE-Juel1)VDB44599$$aKlein-Seetharaman, J.$$b7$$uFZJ
000007755 7001_ $$0P:(DE-HGF)0$$aObinger, C.$$b8
000007755 7001_ $$0P:(DE-HGF)0$$aKagan, V.E.$$b9
000007755 773__ $$0PERI:(DE-600)1472210-0$$a10.1021/ja904343c$$gVol. 131, p. 11288 - 11289$$p11288 - 11289$$q131<11288 - 11289$$tJournal of the American Chemical Society$$v131$$x0002-7863$$y2009
000007755 8567_ $$uhttp://dx.doi.org/10.1021/ja904343c
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