Flavoprotein redox potential

NADH and reduced substrate dehydrogenase-flavoproteins (FPH2) must be continually reoxidized for mitochondrial oxidations to proceed. This is achieved by the electron transport chain (respiratory chain) which is a series of redox carriers of graded redox potential in the inner mitochondrial membrane (Appendix 1) that catalyzes the net reactions ... 

Ubiquinone or Q (coenjyme Q) (Figure 12-5) finks the flavoproteins to cytochrome h, the member of the cytochrome chain of lowest redox potential. Q exists in the oxidized quinone or reduced quinol form under aerobic or anaerobic conditions, respectively. The structure of Q is very similar to that of vitamin K and vitamin E (Chapter 45) and of plastoquinone, found in chloroplasts. Q acts as a mobile component of the respiratory chain that collects reducing equivalents from the more fixed flavoprotein complexes and passes them on to the cytochromes. 

Electron mediators successfully used with oxidases include 2,6-dichlorophenolindophol, hexacyanoferrate-(III), tetrathiafulvalene, tetracyano-p-quinodimethane, various quinones and ferrocene derivatices. From Marcus theory it is evident that for long-range electron transfer the reorganization energies of the redox compound have to be low. Additionally, the redox potential of the mediator should be about 0 to 100 mV vs. standard calomel electrode (SCE) for a flavoprotein (formal potential of glucose oxidase is about -450 mV vs SCE) in order to attain rapid vectrial electron transfer from the active site of the enzyme to the oxidized form of the redox species. 

Flavoprotein dehydrogenases usually accept electrons from reduced pyridine nucleotides and donate them to a suitable electron acceptor. The oxidation-reduction midpoint potential of the FAD of the oxidase has been determined by ESR spectroscopy and shown to be -280 mV. The NADP+/ NADPH redox potential is -320 mV and that of the cytochrome b is -245 mV hence, the flavin is thermodynamically capable of accepting electrons from NADPH and transferring them to cytochrome b. As two electrons are transferred from NADPH, although O2 reduction requires only one electron, the scheme of electron transfer shown in Figure 5.8 has been proposed by Cross and Jones (1991). 

The flavodoxins are a group of FMN containing flavoproteins isolated from microorganisms which mediate electron transfer at a low redox potential between the... 

Due to the variety of enzymatic environments in which FAD/ FADH /FADHZ can be held, enzymes that contain them exhibit redox potentials ranging from -0.45 to + 0.15 V at pH 7 (Bugg, 1997). Xenobiotic compounds whose structures suggest they can be reduced via free radical mechanisms or via hydride transfers may be reduced by such flavoproteins. 

In Table IV (40-47), the available data on redox potentials of free nicotinamide, flavin, deazaflavin, representative flavoproteins, and reac-... 

As for chloroplast membranes, various compounds in mitochondrial membranes accept and donate electrons. These electrons originate from biochemical cycles in the cytosol as well as in the mitochondrial matrix (see Fig. 1-9) —most come from the tricarboxylic acid (Krebs) cycle, which leads to the oxidation of pyruvate and the reduction of NAD+ within mitochondria. Certain principal components for mitochondrial electron transfer and their midpoint redox potentials are indicated in Figure 6-8, in which the spontaneous electron flow to higher redox potentials is toward the bottom of the figure. As for photosynthetic electron flow, only a few types of compounds are involved in electron transfer in mitochondria—namely, pyridine nucleotides, flavoproteins, quinones, cytochromes, and the water-oxygen couple (plus some iron-plus-sulfur-containing centers or clusters). 

Flavocytochrome Fumarate Reductase. The flavocytochrome fumarate reductase (Fff) is a soluble periplasmic protein from Shewanella spp. that reduces fumarate but does not oxidize succinate, in contrast to the membrane-bound fumarate reductases that are related to succinate dehydrogenases, and transfer electrons from quinol to fumarate. It is a monomeric protein of 63.8 kDa that is composed of three domains. The N-terminal domain contains four c-type hemes, and the flavin domain contains noncovalently bound FAD and is related to flavoprotein subunits of membrane-bound fumarate reductases and succinate dehydrogenases. There is also a third domain in the flavocytochromes that has considerable flexibility and may be involved in controlling access of substrate to the active site. The macroscopic redox potentials of the fom hemes of Ffr are —102, —146, —196, and -23 8 mV, while that of FAD is —152 mV. The low redox potential of FAD in Ffr compared to that in membrane-bound fumarate reductase (—55 mV) may explain why it is unable to oxidize succinate. 

TheP7007P700 couple has a redox potential of+0.45 V [c/. redox-potential scale in Fig. 2]. The of the Aq/Aq" couple is probably less than -1 V if it is consistent with the in vitro redox-potential value of Chl/Chl of < -1.0 V. The initial charge separation into P700 and Ao would store approximately 1.5 eV out of 1.8 eV of energy of the absorbed 700-nm photon. The redox potential ofthe A,/A," couple is probably -0.8 V. The redox potentials ofthe iron-sulfur centers FeS-X, FeS-B and FeS-A have been experimentally determined to be -0.73, -0.58 and -0.53 V , respectively. The final electron acceptor in photosystem 1 is the [2Fe-2S]-type ferredoxin (Fd) present in the stroma region of the chloroplasts and having a redox potential of -0.4 V. Under iron-deficient growth conditions, a flavoprotein called flavodoxin is synthesized as a replacement acceptor for ferredoxin. 

A final distinction from nicotinamides is that the flavin coenzymes generally form tight non-dissociable non-covalent complexes with the apoenzyme. Nicotinamides are released at the end of each catalytic cycle and so are consumed as substrate as part of the redox stoichiometry. Because flavins are tightly bound to the apoprotein (/irD= 10 -10 " M) the coenzyme must be oxidised/reduced at the end each turnover before the enzyme complex again becomes catalytically active. Differential binding of flavin and dihydroflavin is responsible for the wide range of redox potentials for flavoproteins so that oxidation or reduction can be thermodynamically favourable. For example, D-amino acid oxidase binds FAD with a dissociation constant of 10 M but FADHj with one of 10 M which changes the reduction potential from —200 for the FAD/FADHj couple free in solution to 0 mV when bound to the enzyme. 

Electron transfer flavins, ETF flavoproteins (see Flavin enzymes) which mediate electron transport from reduced FADH to the cytochrome system. Flavoproteins oxidize those substrates of the Respiratory chain (see) whose oxidation does not involve pyridine nucleotides. However, the substrate must have a more positive redox potential than the NADH -I- H /NAD system. ETF from pork liver has 6 molecules flavin per atom of iron, and copper is also present. 

Reversed electron transport reversal of Oxidative phosphorylation (see) in which NAD is reduced by an ATP-dependent reverse transport of electrons. R.e.t. occurs in organisms that oxidize hydrogen donors whose redox potential (see Oxidation) is more positive than that of the pjmdine nucleotide coenzymes, and it operates in the oxidation of substrates not specific for NAD (see Respiratory chain), e.g. Succinate + NAD - Fumate + NADH + H. Tlie redox system succinate/fumarate (E o = -tO - 031V) is 325 mV more positive than the redox system NAJD / NADH + H (E o =-0.32 V) electrons are passed firom succinate to flavoprotein in the respiratory chain, then via NADH-dehydrogenase to NAD. R.e.t. has been shown in nitrate bacteria (Nitrobac-ter), insect flight muscle mitochondria and kidney mi-... 

These dithiol-flavoproteins transport electrons over a redox potential range considerably more reducing than is associated with free flavin and most other types of flavin enzymes. By acting in conjunction with the protein dithiol centre, flavin is transformed into a much more powerful reducing agent. 

Flavins are widely recognized by their ability of participate in both one- and two-electron transfer processes, since these compounds can exist in three different redox states oxidized (quinone), one-electron reduced (semiquinone) and two-electron reduced (hydroquinone). The redox potential for the complete reduction of oxidized flavins is about -200 mV, but this value may largely vary in flavoproteins, as a consequence of the protein activity site environment, ranging from —400 mV to +60 mV (Fraaije and Mattevi 2000). Flavins may transfer single electrons, hydrogen atoms and hydride ions. In addition, N5 and C4a of the oxidized flavin molecule are susceptible sites for... 

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