Cytochrome oxidation cycle

The electron transfer properties of the cytochromes involve cycling of the iron between the +2 and +3 oxidation states (Cytochrome)Fe + e" (Cytochrome)Fe ° = -0.3Vto+ 0.4V Different cytochromes have different side groups attached to the porphyrin ring. These side groups modify the electron density in the delocalized iz system of the porphyrin, which in turn changes the redox potential of the iron cation in the heme. 

Figure 1. Scheme for photochemical production of co-reductant to drive the oxidation of hydrocarbons by mimicking the cytochrome-P450 cycle. The SnP sensitized photoredox cycle is on the left the P 50 catalytic cycle is shown on the right. 

Its action has been postulated to be intraneuronal on the oxidation cycle at a phase above the cytochrome b level of the cytochrome oxidase system though its precise mechanism has not been elucidated. It is primarily a neurotoxin with a chemical structure that allows for easy penetration of the blood-brain barrier. 

Fig. 1.7 Cytochrome P450 cycle in drug oxidations RH, parent drug ROH, oxidized metabolite e, electron. (Reproduced with permission from Correia (1992).)...

Fig. 6. Photochemical cycles showing coupling of electron transfer to proton transfer, cytochrome oxidation and quinone exchange in (A) native reaction centers where two Cyt c are oxidized in the cycie, (B) reaction centers where uptake of the first proton is inhibited, and (C) reaction centers where uptake ofthe second proton is inhibited (shading indicates the quinone pool). Figure source (A) Paddock, Rongey, McPherson, Juth, Feher and Okamura (1994) Pathway of proton transfer in bacterial reaction centers role of aspartate-L21Z in proton transfers associated with reduction of quinone to dihydroquinone. Biochemistry 33 734 (B) Okamura and Feher (1992) Proton transfer in reaction centers from photosynthetic bacteria. Annu Rev Biochemistry. 61 868 (C) Feher, Paddock, Rongey and Okamura (1992) Proton transfer pathways in photosynthetic reaction centers studied by site-directed mutagenesis. In A Pullman, J Jortner and B Pullman (eds) Membrane Proteins Structures, Interactions and Models, p 485. Kluwer.

Aerobic organisms produce minor fluxes of superoxide ion during respiration and oxidative metabolism. Thus, up to 15% of the O2 reduced by cytochrome-c oxidase and by xanthine oxidase passes through the HOO /O2 - state.70 The reductase of the latter system is a flavoprotein i that probably reduces O2 to HOOH via a redox cycle similar to that outlined by Eqs. (7-19) - (7-22). Thus, the observed flux of O2 -, which is the carrier of the auto-oxidation cycle, is due to leakage during turnover of xanthine/xanthine oxidase (see Scheme 7-14 for a reasonable mechanistic pathway). 

Insects poisoned with rotenone exhibit a steady decline ia oxygen consumption and the iasecticide has been shown to have a specific action ia interfering with the electron transport iavolved ia the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD) by cytochrome b. Poisoning, therefore, inhibits the mitochondrial oxidation of Krebs-cycle iatermediates which is catalysed by NAD. 

N—Fe(IV)Por complexes. Oxo iron(IV) porphyrin cation radical complexes, [O—Fe(IV)Por ], are important intermediates in oxygen atom transfer reactions. Compound I of the enzymes catalase and peroxidase have this formulation, as does the active intermediate in the catalytic cycle of cytochrome P Q. Similar intermediates are invoked in the extensively investigated hydroxylations and epoxidations of hydrocarbon substrates cataly2ed by iron porphyrins in the presence of such oxidizing agents as iodosylbenzene, NaOCl, peroxides, and air. 

Two and twelve moles of ATP are produced, respectively, per mole of glucose consumed in the glycolytic pathway and each turn of the Krebs (citrate) cycle. In fat metaboHsm, many high energy bonds are produced per mole of fatty ester oxidized. Eor example, 129 high energy phosphate bonds are produced per mole of palmitate. Oxidative phosphorylation has a remarkable 75% efficiency. Three moles of ATP are utilized per transfer of two electrons, compared to the theoretical four. The process occurs via a series of reactions involving flavoproteins, quinones such as coenzyme Q, and cytochromes. 

In the third complex of the electron transport chain, reduced coenzyme Q (UQHg) passes its electrons to cytochrome c via a unique redox pathway known as the Q cycle. UQ cytochrome c reductase (UQ-cyt c reductase), as this complex is known, involves three different cytochromes and an Fe-S protein. In the cytochromes of these and similar complexes, the iron atom at the center of the porphyrin ring cycles between the reduced Fe (ferrous) and oxidized Fe (ferric) states. 

The second half of the cycle (Figure 21.12b) is similar to the first half, with a second molecule of UQHg oxidized at the Q site, one electron being passed to cytochrome C and the other transferred to heme bj and then to heme bfj. In this latter half of the Q cycle, however, the bn electron is transferred to the semiquinone anion, UQ , at the Q site. With the addition of two from... 

Cytochrome c oxidase contains two heme centers (cytochromes a and %) as well as two copper atoms (Figure 21.17). The copper sites, Cu and Cug, are associated with cytochromes a and respectively. The copper sites participate in electron transfer by cycling between the reduced (cuprous) Cu state and the oxidized (cupric) Cu state. (Remember, the cytochromes and copper sites are one-electron transfer agents.) Reduction of one oxygen molecule requires passage of four electrons through these carriers—one at a time (Figure... 

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. 

Moreover, an electron transfer chain could be reconstituted in vitro that is able to oxidize aldehydes to carboxylic acids with concomitant reduction of protons and net production of dihydrogen (213, 243). The first enzyme in this chain is an aldehyde oxidoreductase (AOR), a homodimer (100 kDa) containing one Mo cofactor (MOD) and two [2Fe—2S] centers per subunit (199). The enzyme catalytic cycle can be regenerated by transferring electrons to flavodoxin, an FMN-con-taining protein of 16 kDa (and afterwards to a multiheme cytochrome and then to hydrogenase) ... 

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