NADH-dehydrogenase complex

NADH is oxidized by NADH dehydrogenase (complex I), delivering its electrons into the chain and returning as NAD to enzymes that require it. The electrons are passed along a series of protein and lipid carriers that serve as the wire. These include, in order ... 

NADH dehydrogenase (complex I) accepts electrons from NADH... 

Espositi, M.D., Ghelli, A., Batta, M., Cortes, D., and Estornell, E. Natural substances (acetogenins) from the family Annonaceae are potent inhibitors of mitochondrial NADH dehydrogenase (complex I). Biochem.., 301, 161, 1994. 

NAD-linked dehydrogenases remove two hydrogen atoms from their substrates. One of these is transferred as a hydride ion ( II ) to NAD+ the other is released as H+ in the medium (see Fig. 13-15). NADH and NADPH are water-soluble electron carriers that associate reversibly with dehydrogenases. NADH carries electrons from catabolic reactions to their point of entry into the respiratory chain, the NADH dehydrogenase complex described below. NADPH generally supplies electrons to anabolic reactions. Cells maintain separate pools of NADPH and NADH, with different redox potentials. This is accomplished by holding the ratios of [reduced form]/[oxidized form] relatively high for NADPH and relatively low for NADH. Neither NADH nor NADPH can cross the inner mitochondrial membrane, but the electrons they carry can be shuttled across indirectly, as we shall see. 

Shuttle systems convey reducing equivalents from cytosolic NADH to mitochondrial NADH. Reducing equivalents from all NAD-linked dehydrogenations are transferred to mitochondrial NADH dehydrogenase (Complex I). 

Oxidation-Reduction Reactions The NADH dehydrogenase complex of the mitochondrial respiratory chain promotes the following series of oxidation-reduction reactions, in which Fe3+ and Fez+ represent the iron in iron-sulfur centers, Q is ubiquinone, QH2 is ubiquinol, and E is the enzyme ... 

For each of the three reactions catalyzed by the NADH dehydrogenase complex, identify (a) the electron donor, (b) the electron acceptor, (c) the conjugate redox pair, (d) the reducing agent, and (e) the oxidizing agent. 

By disrupting the mitochondrial inner membrane with detergents, Yousef Hatefi, David Green, and others found that all of the major electron carriers except for cytochrome c and UQ occur in the form of four large complexes (fig. 14.8). The isolated NADH dehydrogenase complex (complex I)... 

Complex I The NADH Dehydrogenase Complex. The NADH dehydrogenase complex is the largest complex in the mitochondrial inner membrane. It has some 26 different polypeptides, including approximately seven iron-sulfur centers and a flavoprotein with bound FMN. NADH probably reacts with the FMN, reducing it to FMNH2, and the reduced flavin then transfers electrons to an iron-sulfur center (fig. 14.9). Electrons then move from one iron-sulfur center to another, and eventually to UQ. 

Fig. 3.13. Complex I. A, the map shows how Complex I can be dissected into subcomplexes. Treatment with chaotropic agents splits the Complex into three fractions an iron-sulphur protein (ISP), a flavoprotein (NADH dehydrogenase) complex, and a hydrophobic residue. The figure shows the polypeptide composition and the flavin and iron content of these subcomplexes. ISP can be further split into three FeS-containing fractions by trichloroacetate. See text for details and references. B, the topography of the components mapped in A has been studied by Ragan et al. [290,296]. The NADH-binding site is in the flavoprotein fraction [297]. This, as well as the FeS protein complex (ISP), are possibly buried in the membrane and shielded from phospholipids by the hydrophobic residue (HR). Adapted from Refs. 290, 296.

NAD does not show fluorescence, whereas in NAD or NADH dehydrogenase complexes the fluorescence at 340 nm is reduced after irradiation at 280 nm. In the excitation spectrum of NADH-enzyme complexes increased fluorescence of the coenzyme is recorded after irradiation at 340 nm (Figs. 

Then what will happen if NADH dehydrogenase complex (NADH active site) is inhibited and TCA cycle is still running. We can guess probable results by thought experiment as follows ... 

A scheme improving hydrogen yield was proposed for the hydrogen production by fermentation and the improvement using facultative anaerobic bacteria is shown to be expectable to get the maximum yield. But actual experiments are still under preparation. Although we have to wait the decision of feasibility in future experiments, it is need to pay efforts to find strains lacking the NADH dehydrogenase complex in the wild or mutant strains. 

Complex I, also referred to as the NADH dehydrogenase complex, catalyzes the transfer of electrons from NADH to UQ. The major sources of NADH include several reactions of the citric acid cycle (see pp. 284-287), and fatty acid oxidation (Chapter 12). Composed of at least 25 different polypeptides, complex I is the largest protein component in the inner membrane. In addition to one molecule of FMN, the complex contains seven iron-sulfur centers (Figure 10.2). Iron-sulfur centers, which may consist of two or four iron atoms complexed with an equal number of sulfide ions, mediate 1-electron transfer reactions. Proteins that contain iron-sulfur centers are often referred to as nonheme iron proteins. Although the structure and function of complex I are still poorly understood, it is believed that NADH reduces FMN to FMNH2. Electrons are then transferred from FMNH2 to an iron-sulfur center, 1 electron at a time. After transfer from one iron-sulfur center to another, the electrons are eventually donated to UQ (Figure 10.3). 

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