Coenzyme Q-10 CoQ

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). 

The first of these new, electron transferring components was coenzyme Q (CoQ). Festenstein in R.A. Morton s laboratory in Liverpool had isolated crude preparations from intestinal mucosa in 1955. Purer material was obtained the next year from rat liver by Morton. The material was lipid soluble, widely distributed, and had the properties of a quinone and so was initially called ubiquinone. Its function was unclear. At the same time Crane, Hatefi and Lester in Wisconsin were trying to identify the substances in the electron transport chain acting between NADH and cytochrome b. Using lipid extractants they isolated a new quininoid coenzyme which showed redox changes in respiration. They called it coenzyme Q (CoQ). CoQ was later shown to be identical to ubiquinone. 

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. 

Figure 4-5. The structure of coenzyme Q (CoQ), or ubiquinone. Hydrogen atoms can bind, one at a time, as indicated by the arrows.

The hydrogens are accepted by FAD, which is covalently bound to the apoprotein via a histidine residue. In many flavoproteins, the flavin nucleotide is bound to the apoprotein not covalently but rather via ionic linkages with the phosphate group. The reducing equivalents of FADH2 are passed on to coenzyme Q (CoQ or Q) via the iron-sulfur centers. Thus, the overall reaction catalyzed by complex II is... 

Coenzyme Q (CoQ), also called ubiquinone, is the only electron carrier in the respiratory chain that is not a protein-bound prosthetic group. It is a carrier of hydrogen atoms, that is, protons plus electrons. The oxidized qulnone form of CoQ can accept a single electron to form a semlqulnone, a charged free radical denoted by CoQ -. Addition of a second electron... 

A FIGURE 8-16 Oxidized and reduced forms of coenzyme Q (CoQ), which carries two protons and two electrons. 

Each complex contains one or more electron-carrying prosthetic groups iron-sulfur clusters, flavins, heme groups, and copper ions (see Table 8-2). Cytochrome c, which contains heme, and coenzyme Q (CoQ) are mobile electron carriers. 

Coenzyme Q (CoQ) - CoQ is a benzoquinone linked to a number of isoprene units (usually 10 in mammalian cells and 6 in bacteria). The isoprenoid tail gives the molecule its apolar character, which allows CoQ to diffuse rapidly through the inner mitochondrial membrane. CoQ has the ability to accept electrons in pairs and pass them one at a time through a semiquinone intermediate to Complex III (see here). This cycle is referred to as... 

Coenzyme Q (CoQ) is a quinone found in the cells of all aerobic organisms. It is also called ubiquinone because it is ubiquitous (found everywhere) in nature. Its function is to carry electrons in the electron-transport chain. The oxidized form of CoQ accepts a pair of electrons from a biological reducing agent such as NADH and ultimately transfers them to O2. 

One of the major sites of superoxide generation is Coenzyme Q (CoQ) in the mitochondrial electron transport chain (Fig. 24.5). The one-electron reduced form of CoQ (CoQH ) is free within the membrane and can accidentally transfer an electron to dissolved O2, thereby forming superoxide. In contrast, when O2 binds to cytochrome oxidase and accepts electrons, none of the Q2 radical intermediates are released from the enzyme, and no ROS are generated. 

Ubiquinone One of a scries of quinones, collectively called coenzyme Q (CoQ), u.scd ill biological rcduclioiis of tixygcn. 

Complex I The hrst complex, NADH-CoQ oxidoreductase, catalyzes the first steps of electron transport, namely the transfer of electrons from NADH to coenzyme Q (CoQ). This complex is an integral part of the inner mitochondrial membrane and includes, among other suhunits, several proteins that contain an iron-sulfur cluster and the flavoprotein that oxidizes NADH. (The total number of subunits is more than 20. This complex is a subject of active research, which has proven to he a challenging task because of its complexity. It is particularly difficult to generalize about the nature of the iron—sulfur clusters because they vary from species to species.) The flavoprotein has a flavin coenzyme, called flavin mononucleotide, or FMN, which differs from FAD in not having an adenine nucleotide (Figure 20.4). 

One mechanism that has been proposed to explain the hepatotoxicity of 1,1,2-trichloroethane is the generation of free radical intermediates from reactive metabolites of 1,1,2-trichloroethane (acyl chlorides). Free radicals may stimulate lipid peroxidation which, in turn, may induce liver injury (Albano et al. 1985). However, Klaassen and Plaa (1969) found no evidence of lipid peroxidation in rats given near-lethal doses of 1,1,2-trichloroethane by intraperitoneal injection. Takano and Miyazaki (1982) determined that 1,1,2-trichloroethane inhibits intracellular respiration by blocking the electron transport system from reduced nicotinamide adenine dinucleotide (NADH) to coenzyme Q (CoQ), which would deprive the cell of energy required to phosphorylate adenosine diphosphate (ADP) and thereby lead to depletion of energy stores. 

The first electron carrier in the electron transport chain is an enzyme that contains a tightly bound coenzyme. The coenzyme has a structure similar to FAD. The enzyme formed by the combination of this coenzyme with a protein is called flavin mononucleotide (FMN). Two electrons and one ion from NADH plus another H ion from a mitochondrion pass to FMN, then to an iron-sulfur (Fe—S) protein, and then to coenzyme Q (CoQ). CoQ is also the entry point into the electron transport chain for the two electrons and two H ions from FADH2. As NADH and FADH2 release their hydrogen atoms and electrons, NAD and FAD are regenerated for reuse in the citric acid cycle. 

Nature makes much use of this type of reversible oxidation-reduction to transport a pair of electrons from one substance to another in enzyme-catalyzed reactions. Important compounds in this respect are the compounds called ubiquinones (from ubiquitous + quinone—these quinones are found within the inner mitochondrial membrane of every living cell). Ubiquinones are also called coenzymes Q (CoQ). 

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... 

Nature makes use of the benzoquinone-hydroquinone redox couple in reversible oxidation reactions. These processes are part of the comphcated cascade by which oxygen is used in biochemical degradations. An important series of compounds used for this purpose are the ubiquinones (a name coined to indicate their ubiquitous presence in nature), also collectively called coenzyme Q (CoQ, or simply Q). The ubiquinones are substimted p-benzoquinone derivatives bearing a side chain made up of 2-methylbutadiene units (isoprene Sections 4-7 and 14-10). An enzyme system that utilizes NADH (Real Life 8-1 and 25-2) converts CoQ into its reduced form (QH2). 

Quinones of various types play important roles in cells. One of these quinones is coenzyme Q (CoQ). It is synthesized by most organisms, including humans. Coenzyme Q is also called ubiquinone a pun on its apparently ubiquitous occurrence in nature. Ubiquinone is a 1,4-quinone. Its ring... 

Electron transport begins when NADH transfers hydrogen ions and electrons to complex I and forms the oxidized coenzyme NAD. The hydrogen ions and electrons are transferred to the mobile electron carrier coenzyme Q (CoQ), which carries electrons to complex II. The overall reaction in complex I is written as follows ... 

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