Oxidative phosphorylation scheme

Arbusov reaction of thienyl halides with phosphites in the presence of nickel catalyst [41, 42], or palladium catalyzed phosphorylation of thienyl halides [43], and some of them are commercially available (Scheme 22). 2,5-Diphosphorylthiophenes were synthesized by Arbusov reaction of thienyl halides with phosphites in the presence of nickel catalyst [44] or reaction of 2,5-dilithiothiophene with phosphorus halides followed by oxidation [45] (Scheme 23). 

Figure 20-8 Perspective of the metabolic scheme whereby carbohydrates, fats, and proteins in foodstuffs are oxidized to C02, showing the link between glycolysis, the citric acid cycle, and oxidative phosphorylation...

A quantitative description of oxidative phosphorylation within the cellular environment can be obtained on the basis of nonequilibrium thermodynamics. For this we consider the simple and purely phenomenological scheme depicted in Fig. 1. The input potential X0 applied to the converter is the redox potential of the respiratory substrates produced in intermediary metabolism. The input flow J0 conjugate to the input force X0 is the net rate of oxygen consumption. The input potential is converted into the output potential Xp which is the phosphate potential Xp = -[AG hoS -I- RT ln(ATP/ADP P,)]. The output flow Jp conjugate to the output force Xp is the net rate of ATP synthesis. The ATP produced by the converter is used to drive the ATP-utilizing reactions in the cell which are summarized by the load conductance L,. Since the net flows of ATP are large in comparison to the total adenine nucleotide pool to be turned over in the cell, the flow Jp is essentially conservative. 

This experimental verification entitles us to apply the theory of linear energy converters to oxidative phosphorylation.2 Kedem and Caplan have introduced a useful normalization of the straight and the cross coefficients of the scheme [equations (1) and (2)]. 

Fig. 7. Reaction scheme for oxidative phosphorylation with load and adenylate kinase. LP, conductance of phosphorylation Lt, load conductance and Z.Ak conductance of adenylate kinase reaction. For details see text.

For this simulation we took again the model as was used for the previous calculations of the steady state adenine nucleotides, namely, oxidative phosphorylation with an attached load plus the adenylate kinase reaction. The only modification introduced into this scheme now was to consider a fluctuating rather than a constant load conductance. In order to arrive at a realistic description, a stationary process with a Lorentzian... 

Fig. 10. Operational scheme of oxidative phosphorylation. For further details see text.

Note also that, from a physicochemical point of view, in all schemes reflecting A/ZII-dependent transport systems on both sides of the membrane, H+ ions may be taken for a catalyst, which intensifies the proceeding of definite processes, either oxidative phosphorylation, osmotic work or other types of work. 

As follows from this scheme, secondary reaction (oxidative phosphorylation) products are formed first due to the membrane catalysis effect after bound water dissociation to H+ and OH only the primary reaction (respiration) product—the water molecule—is formed with the help of H+ ions. Thus, the maximum yield of primary reaction products is observed only in the case of the maximum yield of the secondary reaction. 

NADH-ubiquinone reductase was isolated by Hatefi et al. in 1961 (27-B9). A procedure was developed for the resolution of the mitochondrial electron transport system into four enzyme complexes. Recently, a fifth fraction, which is capable of energy conservation and ATP-Pi exchange, was also isolated (30, 31). The overall scheme for the isolation of the five component enzyme complexes of the mitochondrial electron transport-oxidative phosphorylation system is given in Fig. 1. It is seen... 

Fig. 1.3. A scheme of oxidative phosphorylation according to the chemiosmotic coupling hypothesis.

Both groups of reactions are found in bacteria (14), all higher animals (i5), and plants (16) however, oxidative phosphorylation is responsible for 90 % of the oxygen consumed (i 7). Oxidative phosphorylation is driven by the respiratory electron-transport system that is embedded in the lipoprotein inner membrane of eukaryotic mitochondria and in the cell membrane of prokaryotes. It consists of four complexes (Scheme I). The first is composed of nicotinamide adenine dinucleotide (NADH) oxidase, flavin mononucleotide (FMN), and nonheme iron-sulfur proteins 18,19), and it transfers electrons from NADH to ubiquinone. The second is composed of succinate dehydrogenase (SDH), flavin adenine dinucleotide (FAD), and nonheme iron-sulfur proteins (20), and it transfers electrons from succinate to ubiquinone 21, 22). The third is composed of cytochromes b and c, and nonheme iron-sulfur proteins (23), and it transfers electrons from ubiquinone (UQ) to cytochrome c 24). The fourth complex consists of cytochrome c oxidase [ferrocytochrome c 0 oxidoreductase EC 1.9.3.1 25)] which transfers electrons from cytochrome c to O2 26, 27). 

The energy input is accomplished by a proton gradient/flux for the oxidation of a phosphate base [HO transfer from HOP(O)O )2]. The oxidized product is stabilized by the nucleophilic addition of ADP to give ATP. Scheme 8-9 outlines the several steps of the energy-input and energy-output cycles in oxidative phosphorylation. The net transduction is the neutralization (via a singleelectron transfer) of a hydroxide adduct [HOP(O)(O )2] (the one-electron reductant) by a hydronium ion (H3O+)... 

Nessi et al. (Nl) succeeded in rupturing the PMN membrane by adding heparin to the cell suspension. The oxygen consumption, which was measured by a photometric method, could be stimulated by the addition of ADP. An oxygen curve in stage 3, an acceptor control index, and an oxidative phosphorylation quotient with different substrates were obtained according to the scheme of Chance and Williams (Cl). 

The dehydration of (/ )-2-hydroxyglutarate to glutaconate has been studied by Buckel and co-workers (229, 2S0), who have found that the syn elimination of ( )-2-hydroxyglutarate requires a prior activation of the enzyme from cell-free extracts of A. fermentans by ATP, NADH, and MgCl2. The enzymic reaction requires a dithiol, acetyl phosphate, and CoASH, as well as strictly anaerobic conditions, because the active enzyme is irreversibly inactivated on contact with oxygen. Evidence was presented that the adenylation of the protein may be a requisite for activation. Based on preliminary EPR studies and the inactivation of the enzymic reaction by hydroxylamine and uncouplers of oxidative phosphorylation (such as azide, arsenate, and 2,4-dinitrophenol), Schweiger and Buckel postulated a radical mechanism for 2-hydroxyglutarate dehydration via the hydroxyl radical (Scheme 53) (229). Hence, the ATP/NADH-dependent ac-... 

Quinones are firmly established in photosynthesis models. But how about vitamins E and K How do quinones work in animals First of all they transport electrons in a similar way as in photosynthesis (Metzler, 1977 Voet, 1990). Second, tocopherol is known to act as an antioxidant or radical quencher. The radical chain starting with the decomposition of unsaturated lipid peroxides, for example, is inhibited by tocopherol, which produces long-lived semiquinone radicals (Scheme 7.2.10). Vitamin E prevents, for example, sterility in rats fed rancid lipids. Vitamin E in connection with carotenes is also used as a stabilizer for diet margarines containing large amounts of essential fatty acids. Another possible activity of tocopherol is participation in oxidative phosphorylation a hydroquinone is mono-esterified with phosphoric acid to form a quinol phosphate and then oxidized to the quinone. The cationic quinone-phosphate adduct then reacts with anionic phosphate to form pyrophosphate (Scheme 7.2.10), (Wang, 1969 Breslow, 1980 Isler and Brubacher, 1982). 

EXAMPLE 10.13 Which compounds are recycled during the operation of the overall scheme of oxidative phosphorylation ... 

Chlorfenapyr (52 1995, Pirate , ACC/BASF) [119], a potent uncoupler of mitochondrial oxidative phosphorylation [120], is based on a trifluoromethyl substituted pyrrole (Scheme 35.3). 

With this procedure ot-alkylated (83), brominated (84), formylated (85), silylated (87 and 89), phosphorylated (88) and hydroxylated (90)198.199 phosphetane oxides have been prepared. Usually the products are present as a single diastereomer, with retention of configuration at the phosphorus atom and with the new substituent installed in the equatorial position, in anti disposition to the menthyl group, as confirmed by X-ray crystallography. Cl- and C2-symmetric phosphetane dioxides or diboranes (88, 89 and 91) have also been obtained. Further elaboration has allowed the preparation of derivatives with multiple stereogenic centres (86). Most of the phosphetane oxides of Scheme 2.30 have been reduced to the parent phosphines... 

On the basis of these observations, Martins has proposed a scheme in which vitamin K influences electron transfer between NAD, flavoprotein, and cytochrome b. This view was further supported when a reductase was discovered that catalyzes the oxidation of NADH in the presence of vitamin K. It has not yet been established whether the reduced vitamin K can be oxidized in turn by the respiratory chain. The mechanism by which vitamin K affects oxidative phosphorylation is not clear. 

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