NADH-coenzyme Q

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. 

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). 

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

NADH cytochrome bj Adenylate kinase NADH-coenzyme Q Pyruvate dehydrogenase... 

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. 

See also Electron Transport, NADH, Coenzyme Q, Amytal... 

See also NADH, Coenzyme Q, Inhibitors and Artificial Electron Acceptors... 

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-... 

Hodnick WE, Bohmont CW, Capps C, Pardini RS. Inhibition of mitochondrial NADH-oxidase (NADH-Coenzyme Q oxidoreductase) enzyme system by flavonoids a structure-activity study. Biochem Pharmacol 1987 36 2873-2874. Hodnick WE, Duval DL, Pardini RS. Inhibition of mitochondrial respiration and cyanide-stimulated generation of reactive oxygen species by selected flavonoids. Biochem Pharmacol 1994 47 573-580. 

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

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