Coenzyme electron transfer

Iron Sulfur Compounds. Many molecular compounds (18—20) are known in which iron is tetrahedraHy coordinated by a combination of thiolate and sulfide donors. Of the 10 or more stmcturaHy characterized classes of Fe—S compounds, the four shown in Figure 1 are known to occur in proteins. The mononuclear iron site REPLACE occurs in the one-iron bacterial electron-transfer protein mbredoxin. The [2Fe—2S] (10) and [4Fe—4S] (12) cubane stmctures are found in the 2-, 4-, and 8-iron ferredoxins, which are also electron-transfer proteins. The [3Fe—4S] voided cubane stmcture (11) has been found in some ferredoxins and in the inactive form of aconitase, the enzyme which catalyzes the stereospecific hydration—rehydration of citrate to isocitrate in the Krebs cycle. In addition, enzymes are known that contain either other types of iron sulfur clusters or iron sulfur clusters that include other metals. Examples include nitrogenase, which reduces N2 to NH at a MoFe Sg homocitrate cluster carbon monoxide dehydrogenase, which assembles acetyl-coenzyme A (acetyl-CoA) at a FeNiS site and hydrogenases, which catalyze the reversible reduction of protons to hydrogen gas. 

FIGURE 18.19 The structures and redox states of the nicotinamide coenzymes. Hydride ion (H , a proton with two electrons) transfers to NAD to produce NADH. 

Flavin coenzymes can exist in any of three different redox states. Fully oxidized flavin is converted to a semiqulnone by a one-electron transfer, as shown in Figure 18.22. At physiological pH, the semiqulnone is a neutral radical, blue in color, with a A ax of 570 nm. The semiqulnone possesses a pAl of about 8.4. When it loses a proton at higher pH values, it becomes a radical anion, displaying a red color with a A ax of 490 nm. The semiqulnone radical is particularly stable, owing to extensive delocalization of the unpaired electron across the 77-electron system of the isoalloxazine. A second one-electron transfer converts the semiqulnone to the completely reduced dihydroflavin as shown in Figure 18.22. 

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-... 

Note that flavin coenzymes can carry out either one-electron or two-electron transfers. The succinate dehydrogenase reaction represents a net two-electron reduction of FAD. 

Thenoyltrifluoroacetone and carboxin and its derivatives specifically block Complex II, the succinate-UQ reductase. Antimycin, an antibiotic produced by Streptomyees griseus inhibits the UQ-cytochrome c reductase by blocking electron transfer between bn and coenzyme Q in the Q site. Myxothiazol inhibits the same complex by acting at the site. 

The redox properties of quinones are crucial to the functioning of living cells, where compounds called ubiquinones act as biochemical oxidizing agents to mediate the electron-transfer processes involved in energy production. Ubiquinones, also called coenzymes Q, are components of the cells of all aerobic organisms, from the simplest bacterium to humans. They are so named because of their ubiquitous occurrence in nature. 

Scheme 2 Mechanism of repair of cyclobutane pyrimidine dimers (CPD) by a CPD photolyase. 8-HDF 8-hydroxy-5-deazaflavin, ET electron transfer. FADH reduced and de-protonated flavin-coenzyme...

We next focus on the use of fixed-site cofactors and coenzymes. We note that much of this coenzyme chemistry is now linked to very local two-electron chemistry (H, CH3", CH3CO-, -NH2,0 transfer) in enzymes. Additionally, one-electron changes of coenzymes, quinones, flavins and metal ions especially in membranes are used very much in very fast intermediates of twice the one-electron switches over considerable electron transfer distances. At certain points, the chains of catalysis revert to a two-electron reaction (see Figure 5.2), and the whole complex linkage of diffusion and carriers is part of energy transduction (see also proton transfer and Williams in Further Reading). There is a variety of additional coenzymes which are fixed and which we believe came later in evolution, and there are the very important metal ion cofactors which are separately considered below. 

Haem, Fe Chlorophyll, Mg Coenzyme B12, Co Factor F-430, Ni Electron transfer in membranes and elsewhere Light capture and transduction in membranes Transfer of methyl, rearrangements of substrates Activation of carbon monoxide... 

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... 

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). 

The first of these new, electron transferring components was coenzyme Q (CoQ). Festenstein in R.A. Morton s laboratory in Liverpool had isolated crude preparations from intestinal mucosa in 1955. Purer material was obtained the next year from rat liver by Morton. The material was lipid soluble, widely distributed, and had the properties of a quinone and so was initially called ubiquinone. Its function was unclear. At the same time Crane, Hatefi and Lester in Wisconsin were trying to identify the substances in the electron transport chain acting between NADH and cytochrome b. Using lipid extractants they isolated a new quininoid coenzyme which showed redox changes in respiration. They called it coenzyme Q (CoQ). CoQ was later shown to be identical to ubiquinone. 

Scheme 2 Model of the membrane-bound electron transfer of Methanosarcina mazei G61 according to Ref. [29]. MP=methanophenazine dihydro-MP=dihydromethanophenazine CoM-SH=coenzyme M CoB-SH=coenzyme B p420=coenzyme F420 p42oH2=reduced form of the coenzyme F420...

Ferredoxins (Fds) are widespread in the three domains of life and an abundance of sequence data and structural information are available for Fds isolated from several sources. In particular, the bacterial type Fds are small electron-transfer proteins that posses cubane xFe-yS clusters attached to the protein matrix by Fe ligation of Cys via a conserved consensus ligating sequence. The archaeal type ferredoxins are water-soluble electron acceptors for the acyl-coenzyme A forming 2-oxoacid/ferredoxin oxidoreductase, a key enzyme involved in the central archaeal metabolic pathways. Fds have been distinguished according to the number of iron and inorganic sulphur atoms, 2Fe-2S, 4Fe-4S/3Fe-4S (Fig. Ib-d) and Zn-containing Fds. 

Figure 7.12 The process of p-oxidation of fatty acyl-CoA in mitochondria. This cycle of reactions converts all the carbon atoms in fatly acyl-CoA to acetyl-CoA which is oxidised in the Krebs cycle. In the first oxidation, hydrogen atoms are transferred to FAD and in the second to NAD. Both reduced coenzymes are oxidised via the electron transfer pathway.

The connections between the phases are provided by coenzymes, which become reduced in glycolysis, P-oxidation and the Krebs cycle and, subsequently, transfer hydrogen atoms or electrons into the electron transfer chain. These are ultimately oxidised by oxygen, and ATP is generated. 

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... 

Biosensors constructed for ethanol and D-glucose measurements in beverages were built using ferrocene compounds as electron transfer mediators between the coenzyme PQQ of immobilized enzymes glucose (GDH) and alcohol (ADH) dehydrogenases and a carbon electrode surface <2003JOM(668)83>. 

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