NADH coenzyme Q reductase

NADH coenzyme Q reductase defect (complex I) Succinate coenzyme Q reductase defect (complex II) Coenzyme Q cytochrome C reductase defect (complex III)... 

Iron centers undergo cyclic oxidoreduction between ferrous and ferric states, as shown here. Complex I is also called NADH-coenzyme Q reductase because the electrons are used to reduce coenzyme Q. The passage through Complex I can be blocked by the compounds rotenone and amytal and the artificial electron acceptor methylene blue can accept electrons from FMNH2 Figure 15.9. 

A protein complex capable of rapidly reducing coenzyme Q in the presence of succinate (succinic coenzyme Q reductase), NADH (NADH coenzyme Q reductase), and cytochrome c (cytochrome c coen-... 

Respiratory-chain disorders (with mitochondrial myopathy) Lactic Various, including cytochromes b, aa, cytochrome c oxidase, NADH-coenzyme Q reductase 15.6... 

Abnormalities of the respiratoiy chain. These are increasingly identified as the hallmark of mitochondrial diseases or mitochondrial encephalomyopathies [13]. They can be identified on the basis of polarographic studies showing differential impairment in the ability of isolated intact mitochondria to use different substrates. For example, defective respiration with NAD-dependent substrates, such as pyruvate and malate, but normal respiration with FAD-dependent substrates, such as succinate, suggests an isolated defect of complex I (Fig. 42-3). However, defective respiration with both types of substrates in the presence of normal cytochrome c oxidase activity, also termed complex IV, localizes the lesions to complex III (Fig. 42-3). Because frozen muscle is much more commonly available than fresh tissue, electron transport is usually measured through discrete portions of the respiratory chain. Thus, isolated defects of NADH-cytochrome c reductase, or NADH-coenzyme Q (CoQ) reductase suggest a problem within complex I, while a simultaneous defect of NADH and succinate-cytochrome c reductase activities points to a biochemical error in complex III (Fig. 42-3). Isolated defects of complex III can be confirmed by measuring reduced CoQ-cytochrome c reductase activity. 

As its name implies, this complex transfers a pair of electrons from NADH to coenzyme Q a small, hydrophobic, yellow compound. Another common name for this enzyme complex is NADH dehydrogenase. The complex (with an estimated mass of 850 kD) involves more than 30 polypeptide chains, one molecule of flavin mononucleotide (FMN), and as many as seven Fe-S clusters, together containing a total of 20 to 26 iron atoms (Table 21.2). By virtue of its dependence on FMN, NADH-UQ reductase is a jlavoprotein. 

Electrons enter the ETC at respiratory Complexes I and II. The electrons from NADH enter at respiratory Complex I (RC I, NADH dehydrogenase) with the concomitant oxidation of NADH to NAD+. The electrons carried by FADH2 are transferred to RC II (succinate dehydrogenase) as the FADH2 is oxidized to FAD and succinate is reduced to fumarate. These electrons from RC I and II are transferred to the quinone form of coenzyme Q (CoQ), which delivers them to RC III (UQ-cytochrome c reductase). Cytochrome c then accepts the electrons from RC III, and the reduced cytochrome c is reoxidized as it delivers the electrons to RC IV, cytochrome c oxidase. The electrons are then used by RC IV to reduce molecular oxygen to water. 

The electrons from FMNH2 are transferred to the next electron carrier, coenzyme Q, via the iron-sulfur centers of the NADH-CoQ reductase. The iron-sulfur centers consist of iron atoms paired with an equal number of acid-labile sulfur atoms. The respiratory chain iron-sulfur clusters are of the Fe2S2 or Fe4S4 type. The iron atom, present as nonheme iron, undergoes oxidation-reduction cycles (Fe + Fe + -t- e ). In the Fe4S4 complexes, the centers... 

Electron transport chain Present in the mitochondrial membrane, this linear array of redox active electron carriers consists of NADH dehydrogenase, coenzyme Q, cytochrome c reductase, cytochrome c, and cytochrome oxidase as well as ancillary iron sulfur proteins. The electron carriers are arrayed in order of decreasing reduction potential such that the last carrier has the most positive reduction potential and transfers electrons to oxygen. 

A. Rotenone binds avidly to the flavoprotein NADH CoQ reductase, complex I (also called NADH dehydrogenase). The central portion of the rotenone structure resembles the isoalloxazine ring of the FMN molecule, and when it binds to complex I, rotenone prevents the transfer of electrons from NADH to coenzyme Q. 

Do respiratory inhibitors have a connection with respiratory complexes Many of the workings of the electron transport chain have been elucidated by experiments using respiratory inhibitors. These inhibitors specifically block the transfer of electrons at specific points in the respiratory complexes. Fixamples are GO and CN", both of which block the hnal step of the electron transport chain, and rotenone, which blocks the transfer of electrons from NADH reductase to coenzyme Q. When such a blockage occurs, it causes electrons to pile up behind the block, giving a reduced carrier that cannot be oxidized. By noting which carriers become trapped in a reduced state and which ones are trapped in an oxidized state, we can establish the hnk between carriers. 

Discuss the role of coenzyme Q as a mobile electron carrier between NADH-Q oxidoreductase and cytochrome reductase (Complex 111). 

The involvement of coenzyme Q (CoQ) as an intermediate carrier in some plasma membrane-associated redox activities, such as NADH-ferricyanide and NADH-diferric transferrin reductases and NADH-oxygen oxidoreductase, has been demonstrated (Sun et ai, 1992). CoQ is also required for the maintenance of NADH-AFR reductase, and this distinguishes NADH-AFR reductase from other redox activities related to cis electron transport (i.e., with both donor and acceptor sites located on the same side of the plasma membrane) such as NADH-cytochrome... 

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