Flavoproteins electron-transferring

The struetures of eight flavoprotein electron transfer complexes will be examined (Table 1). Four of these involve flavin to heme electron transfer, three involve electron transfer between flavin and an iron-sulfur center and one involves flavin to flavin electron transfer. These eomplexes provide a variety of domain types and arrangements, cofactor types and interdomain interaetions that can help define the factors important for the electron... 

Stuehr DJ, Tejero J, Haque MM (2009) Structural and mechanistic aspects of flavoproteins electron transfer through the nitric oxide synthase flavoprotein domain. FEBS J 276 3959-3974... 

Access to three different redox states allows flavin coenzymes to participate in one-electron transfer and two-electron transfer reactions. Partly because of this, flavoproteins catalyze many different reactions in biological systems and work together with many different electron acceptors and donors. These include two-electron acceptor/donors, such as NAD and NADP, one- or two-elec-... 

All these intermediates except for cytochrome c are membrane-associated (either in the mitochondrial inner membrane of eukaryotes or in the plasma membrane of prokaryotes). All three types of proteins involved in this chain— flavoproteins, cytochromes, and iron-sulfur proteins—possess electron-transferring prosthetic groups. 

An iron sulfur-flavoprotein that transfers electrons directly to the dioxygenase, as in phthalate dioxygenase (class I)... 

A flavoprotein that transfers electrons to the ferredoxin, as in benzene dioxygenase (class II)... 

FeS Iron-sulfur protein ETF Electron-transferring flavoprotein Ep Elavoprotein Q Ubiquinone Cyt Cytochrome... 

Ma, Y.C., Funk, M., Dunham, W.R. and Komuniecki, R. (1993) Purification and characterization of electron-transfer flavoprotein rhodoquinone oxidoreduc-tase from anaerobic mitochondria of anaerobic mitochondria of the adult parasitic nematode, Ascaris suum. Journal of Biological Chemistry 268, 20360-20365. 

The handling of sulfate by protoaerobes depends upon the initial energised coupling to adenosine phosphate as APS, since sulfate is difficult to reduce. The reductase is a flavoprotein linked to Fe S electron transfer centres. Subsequently, released sulfite is reduced by a haem protein (SIR) in which haem is directly bound... 

R. Hille and R.F. Anderson, Coupled electron/proton transfer in complex flavoproteins — solvent kinetic isotope effect studies of electron transfer in xanthine oxidase and trimethylamine dehydrogenase. J. Biol. Chem. 276, 31193-31201 (2001). 

The primary function of flavoprotein NADPH-cytochrome P-450 reductase is the hydro-xylation of various substrates, which occurs during electron transfer from NADPH to cytochrome P-450 [1] ... 

While cytochrome P-450 catalyzes the interaction with substrates, a final step of microsomal enzymatic system, flavoprotein NADPH-cytochrome P-450 reductase catalyzes the electron transfer from NADPH to cytochrome P-450. As is seen from Reaction (1), this enzyme contains one molecule of each of FMN and FAD. It has been suggested [4] that these flavins play different roles in catalysis FAD reacts with NADPH while FMN mediates electron... 

Glutaric acidurias Type I Primary defect of glutarate oxidation Type II Defect of electron transfer flavoprotein Type I Severe basal ganglia/cerebellar disease with macrocephaly. Onset 1-2 years Type II Fulminant neurological syndrome of the neonate. Often with renal/hepatic cysts. Usually fatal Diet low in lysine and tryptophan Supplementation with coenzyme Q, riboflavin, carnitine... 

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. 

NADH-coenzyme Q (CoQ) oxidoreductase, transfers electrons stepwise from NADH, through a flavoprotein (containing FMN as cofactor) to a series of iron-sulfur clusters (which will be discussed in Chapter 13) and ultimately to CoQ, a lipid-soluble quinone, which transfers its electrons to Complex III. A If, for the couple NADH/CoQ is 0.36 V, corresponding to a AG° of —69.5 kJ/mol and in the process of electron transfer, protons are exported into the intermembrane space (between the mitochondrial inner and outer membranes). 

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). 

Over the years, there have been numerous reports of oxidase preparations that contain polypeptide components, additional to those described above. As yet no molecular probes are available for these, and so their true association with the oxidase is unconfirmed. There are many reports in the literature describing the role of ubiquinone as an electron transfer component of the oxidase, but its involvement is controversial. Quinones (ubiquinone-10) have reportedly been detected in some neutrophil membrane preparations, but other reports have shown that neither plasma membranes, specific granules nor most oxidase preparations contain appreciable amounts of quinone, although some is found in either tertiary granules or mitochondria. Still other reports suggest that ubiquinone, flavoprotein and cytochrome b are present in active oxidase preparations. Thus, the role of ubiquinone and other quinones in oxidase activity is in doubt, but the available evidence weighs against their involvement. Indeed, the refinement of the cell-free activation system described above obviates the requirement for any other redox carriers for oxidase function. 

Cytochrome P-450 has been characterized in four stable states [Fe, Fe " RH, Fe RH, (O2—Fe ) RH (metastable)] during its oxygenase reaction cycle. In the complete native system a flavoprotein and a redoxin (putidaredoxin) act as electron donors but also as effectors that complement the cytochrome. In the more complex microsomal system the sequence and intermediates are less well defined the electron-transfer chain contains two flavoproteins and one cytochrome, whose interactions with cytochrome P-450 are still the subject of great controversy. 

Gomes CM, Vicente JB,Wasserfallen A,Teixeira M. 2000. Spectroscopic studies and characterization of a novel electron-transfer chain from Escherichia coli involving a flavorubredoxin and its flavoprotein reductase partner. Biochemistry 39 16230-7. 

Most compounds oxidized by the electron transport chain donate hydrogen to NAD+, and then NADH is reoxidized in a reaction coupled to reduction of a flavoprotein. During this transformation, sufficient energy is released to enable synthesis of ATP from ADP. The reduced flavoprotein is reoxidized via reduction of coenzyme Q subsequent redox reactions then involve cytochromes and electron transfer processes rather than hydrogen transfer. In two of these cytochrome redox reactions, there is sufficient energy release to allow ATP synthesis. In... 

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