Coenzymes Q

The ready reversibility of this reaction is essential to the role that qumones play in cellular respiration the process by which an organism uses molecular oxygen to convert Its food to carbon dioxide water and energy Electrons are not transferred directly from the substrate molecule to oxygen but instead are transferred by way of an electron trans port chain involving a succession of oxidation-reduction reactions A key component of this electron transport chain is the substance known as ubiquinone or coenzyme Q... 

Two and twelve moles of ATP are produced, respectively, per mole of glucose consumed in the glycolytic pathway and each turn of the Krebs (citrate) cycle. In fat metaboHsm, many high energy bonds are produced per mole of fatty ester oxidized. Eor example, 129 high energy phosphate bonds are produced per mole of palmitate. Oxidative phosphorylation has a remarkable 75% efficiency. Three moles of ATP are utilized per transfer of two electrons, compared to the theoretical four. The process occurs via a series of reactions involving flavoproteins, quinones such as coenzyme Q, and cytochromes. 

Deriva.tives, The most important derivatives of 1,2,3,4-benzenetetrol are the ubiquiaones, eg, coenzyme Q, which are dimethoxytoluquiaones with polyisoprenoid side chains (61). They occur ia plants and animals. Mice with hereditary muscular dystrophy have a deficiency of coenzyme Q ia their heart and hind leg muscles. Therapeutic adrninistration of coenzyme Q /7339-63-5] produces physical improvement and a significantly prolonged lifespan (212). Coenzyme Q also has been used to treat deafness when adrninistered either orally or parenteraHy (213). 

The preparation of coenzyme Q usually iavolves either 2,3-dimethoxy-5-methylbenzoquinone or hydroquiaone as the starting material. Treatment of the hydroquiaone with geranyl bromide followed by oxidation affords (61, n = 2) (214). A facile and efficient preparation of ubiquiaone-10 (61, n = 10) has been developed (215). 

The decline in immune function may pardy depend on a deficiency of coenzyme Q, a group of closely related quinone compounds (ubiquinones) that participate in the mitochondrial electron transport chain (49). Concentrations of coenzyme Q (specifically coenzyme Q q) appear to decline with age in several organs, most notably the thymus. 

Coenzyme Q (Section 24.14) Naturally occurring group of related quinones involved in the chemistry of cellular respiration. Also known as ubiquinone. 

FIGURE 20.14 The succinate dehydrogenase reaction. Oxidation of succinate occurs with reduction of [FAD]. Reoxidation of [FADH9] transfers electrons to coenzyme Q. 

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. 

The final step of the reaction involves the transfer of two electrons from iron-sulfur clusters to coenzyme Q. Coenzyme Q is a mobile electron carrier. Its isoprenoid tail makes it highly hydrophobic, and it diffuses freely in the hydrophobic core of the inner mitochondrial membrane. As a result, it shuttles electrons from Complexes I and II to Complex III. The redox cycle of UQ is shown in Figure 21.5, and the overall scheme is shown schematically in Figure 21.6. 

FIGURE 21.5 (a) The three oxidation states of coenzyme Q. (b) A space-filling model of coenzyme Q. 

In the third complex of the electron transport chain, reduced coenzyme Q (UQHg) passes its electrons to cytochrome c via a unique redox pathway known as the Q cycle. UQ cytochrome c reductase (UQ-cyt c reductase), as this complex is known, involves three different cytochromes and an Fe-S protein. In the cytochromes of these and similar complexes, the iron atom at the center of the porphyrin ring cycles between the reduced Fe (ferrous) and oxidized Fe (ferric) states. 

It should be emphasized here that the four major complexes of the electron transport chain operate quite independently in the inner mitochondrial membrane. Each is a multiprotein aggregate maintained by numerous strong associations between peptides of the complex, but there is no evidence that the complexes associate with one another in the membrane. Measurements of the lateral diffusion rates of the four complexes, of coenzyme Q, and of cytochrome c in the inner mitochondrial membrane show that the rates differ considerably, indicating that these complexes do not move together in the membrane. Kinetic studies with reconstituted systems show that electron transport does not operate by means of connected sets of the four complexes. 

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. 

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