Cytochrome oxygen transfer

This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

Electron-transfer chains in plants differ in several striking aspects from their mammalian counterparts. Plant mitochondria are well known to contain alternative oxidase that couples oxidation of hydroquinones (e.g., ubiquinol) directly to reduction of oxygen. Semiquinones (anion-radicals) and superoxide ions are formed in such reactions. The alternative oxidase thus provides a bypass to the conventional cytochrome electron-transfer pathway and allows plants to respire in the presence of compounds such as cyanides and carbon monoxide. There are a number of studies on this problem (e.g., see Affourtit et al. 2000, references therein). 

Cavalieri E.L. and Rogan, E.G. (2002) Fluoro substitution of carcinogenic aromatic hydrocarbons models for understanding mechanisms of metabolic activation and of oxygen transfer catalyzed by cytochrome P450, in The Handbook of Environmental Chemistry, Vol. 3,... 

Oxometalloporphyrins were taken as models of intermediates in the catalytic cycle of cytochrome P-450 and peroxidases. The oxygen transfer from iodosyl aromatics to sulfides with metalloporphyrins Fe(III) or Mn(III) as catalysts is very clean, giving sulfoxides, The first examples of asymmetric oxidation of sulfides to sulfoxides with significant enantioselectivity were published in 1990 by Naruta et al, who used chiral twin coronet iron porphyrin 27 as the catalyst (Figure 6C.2) [79], This C2 symmetric complex efficiently catalyzed the oxidation... 

Thus, the isotope effect for the allylic oxidation of cyclohexene by cytochrome P 450 is about 5 and is the same for the reconstituted, NADPH-dependent and the peroxide-dependent paths. This similarity suggests that although product ratios may change from one oxygen donor to another, the mechanism of oxygen transfer may be invariant. Efforts to develop a clearer understanding of the relationships between the 02-dependent and peroxide-dependent pathways for oxygen transfer catalyzed by cytochrome P 450 are currently underway. 

The observation that cytochrome P 450 can be driven by hydroperoxides and related oxygen donors suggests that metalloporphyrins can be made to function as oxygen-transfer catalysts in simple model systems. 

Fig. 5.18 Schematic representation of the mechanism of haloperoxidases. In the presence of Cl", HOCI is formed that (a) diffuses from the active site and oxidizes substrates in the medium, although in some cases, (b) oxidation may occur within the active site. In the absence of Cl", thiol-ligated haloperoxidases can (c) catalyze oxygen transfer to their substrates in a cytochrome P450-like reaction...

The activation of oxygen in oxygen transfer reactions is usually mediated by a suitable transition metal catalyst which has to be sufficiently stable under the reaction conditions needed. But also non-metal catalysts for homogeneous oxidations have recently been of broad interest and several of them have been compiled in a recent review.2 Other examples for well known alkene oxidation reactions are the ozonolysis, hydroboration reactions or all biological processes, where oxygen is activated and transferred to the substrate. Examples for these reactions might be cytochrome P450 or other oxotransferases. Of these reactions, this contribution will focus on transition-metal mediated epoxidation and dihydroxylation. 

Cytochrome c transfers electrons to the cytochrome aa3 complex, which transfers the electrons to molecular oxygen, and the oxygen is reduced to water. Cytochromes a and a3 contain heme a and two different proteins containing copper. The energy released by the transfer of electrons from cytochrome c to oxygen is used to pump protons across the inner mitochondrial membrane. Every two electrons that are transferred from cytochrome c to oxygen produce one ATP. 

Mulder, P.P., Devanesan, P., van Alem, K., Lodder, G., Rogan, E.G., Cavalieri, E.L. (2003). Fluorobenzo(a)pyrenes as probes of the mechanism of cytochrome P450-catalyzed oxygen transfer in aromatic oxygenations. Free Radio. Biol. Med. 34 734-45. 

Warburg, O., Negelein, E., Haas, E. (1933). Spektroskopischer Nachweis des sauerstoffiiber-tradenden Ferments neben Cytochrom [Spectroscopic evidence of the oxygen-transferring ferment compared to cytochrome]. Biochemische Zeitschrift, 266, 1-8. 

Other membrane-bound enzymes are known to catalyze oxygen transfer. Among them, cytochrome-P450-dependent monooxygenases catalyze a large number of reaction including the epoxidation of alkenes by molecular oxygen... 

Cytochrome c transfers electrons from cytochrome Ci, the terminal component of complex III, to the four redox centers of the cytochrome oxidase complex. The transfer of four electrons from each of the four redox centers of the cytochrome oxidase complex to an oxygen molecule... 

J. M. Garrison, T. C. Bruice, Intermediates in the epoxidation of alkenes by cytochrome P-450 models. 3. Meclranism of oxygen transfer from substituted oxochromium(V) porphyrins to olefinic substrates, f. Am. Chem. Soc. Ill (1989) 191. 

W. A. Lee, T. C. Bruice, Homolytic and heterolytic oxygen-oxygen bond scissions accompanying oxygen transfer to iron(III) porphyrins by percarboxylic adds and hydroperoxides. A mechanistic criterion for peroxidase and cytochrome P-450, ]. Am. Chem. Soc. 107 (1985) 513. 

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