Coenzyme electron transport chain

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... 

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. 

The TCA cycle can now be completed by converting succinate to oxaloacetate. This latter process represents a net oxidation. The TCA cycle breaks it down into (consecutively) an oxidation step, a hydration reaction, and a second oxidation step. The oxidation steps are accompanied by the reduction of an [FAD] and an NAD. The reduced coenzymes, [FADHg] and NADH, subsequently provide reducing power in the electron transport chain. (We see in Chapter 24 that virtually the same chemical strategy is used in /3-oxidation of fatty acids.)... 

Situated as it is between glycolysis and the electron transport chain, the TCA cycle must be carefully controlled by the ceil. If the cycle were permitted to run unchecked, large amounts of metabolic energy could be wasted in overproduction of reduced coenzymes and ATP conversely, if it ran too slowly, ATP would not be produced rapidly enough to satisfy the needs of the cell. Also, as just seen, the TCA cycle is an important source of precursors for biosynthetic processes and must be able to provide them as needed. 

As we have seen, the metabolic energy from oxidation of food materials—sugars, fats, and amino acids—is funneled into formation of reduced coenzymes (NADH) and reduced flavoproteins ([FADHg]). The electron transport chain reoxidizes the coenzymes, and channels the free energy obtained from these reactions into the synthesis of ATP. This reoxidation process involves the removal of both protons and electrons from the coenzymes. Electrons move from NADH and [FADHg] to molecular oxygen, Og, which is the terminal acceptor of electrons in the chain. The reoxidation of NADH,... 

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. 

FIGURE 24.11 The acyl-CoA dehydrogenase reaction. The two electrons removed in this oxidation reaction are delivered to the electron transport chain in the form of reduced coenzyme Q (UQH9). 

As its name implies, the citric acid cycle is a closed loop of reactions in which the product of the hnal step (oxaloacetate) is a reactant in the first step. The intermediates are constantly regenerated and flow continuously through the cycle, which operates as long as the oxidizing coenzymes NAD+ and FAD are available. To meet this condition, the reduced coenzymes NADH and FADH2 must be reoxidized via the electron-transport chain, which in turn relies on oxygen as the ultimate electron acceptor. Thus, the cycle is dependent on the availability of oxygen and on the operation of the electron-transport chain. 

Ubiquinones (coenzymes Q) Q9 and Qi0 are essential cofactors (electron carriers) in the mitochondrial electron transport chain. They play a key role shuttling electrons from NADH and succinate dehydrogenases to the cytochrome b-c1 complex in the inner mitochondrial membrane. Ubiquinones are lipid-soluble compounds containing a redox active quinoid ring and a tail of 50 (Qio) or 45 (Q9) carbon atoms (Figure 29.10). The predominant ubiquinone in humans is Qio while in rodents it is Q9. Ubiquinones are especially abundant in the mitochondrial respiratory chain where their concentration is about 100 times higher than that of other electron carriers. Ubihydroquinone Q10 is also found in LDL where it supposedly exhibits the antioxidant activity (see Chapter 23). 

The microbes use two general strategies to synthesize ATP respiration and fermentation. A respiring microbe captures the energy released when electrons are transferred from a reduced species in the environment to an oxidized species (Fig. 18.1). The reduced species, the electron donor, sorbs to a complex of redox enzymes, or a series of such complexes, located in the cell membrane. The complex strips from the donor one or more electrons, which cascade through a series of enzymes and coenzymes that make up the electron transport chain to a terminal enzyme complex, also within the cell membrane. 

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. 

FAD is a coenzyme for a large number of oxidation reactions, largely of carbohydrates. Correspondingly, FADH2 is a coenzyme for a number of reduction reactions. Certain of the reactions of FAD and FADH2 are involved in the electron transport chain in mitochondria, associated with the synthesis of ATP. We shall see examples in chapter 17. 

As noted earlier, coenzymes are frequently altered structurally in the course of an enzymatic reaction. However, they are usually reconverted to their original structure in a subsequent reaction, as opposed to being further metabolized. One turn of the citric acid cycle converts NAD+ into NADH, FAD into FADH2, and acetyl-SCoA into CoASH. Coenzyme A is consumed in the metabolism of pyruvate (see below) but regenerated in the citric acid cycle. Both NADH and FADH2 are reconverted into NAD+ and FAD by the electron transport chain. 

In this reaction, pyruvic acid is oxidized to carbon dioxide with formation of acetyl-SCoA and NAD+ is reduced to NADH. As noted in chapter 15, this reaction requires the participation of thiamine pyrophosphate as coenzyme. Here too the NADH formed is converted back to NAD+ by the electron transport chain. As noted above, the acetyl-SCoA is consumed by the citric acid cycle and CoASH is regenerated. 

Electron transport chain a series of multienzyme complexes organized in the inner layer of the mitochondrial membrane that catalyze the transport of electrons from reduced coenzymes to molecular oxygen coupled to the synthesis of ATP. 

Coenzyme QIO (21) is one of the essential enzymes in the mitochondrial electron transport chain, participating in the aerobic respiration cycle. The role of Co-QlO as a cardioprotective substance and an antioxidant are well studied. Recently, it was found that Co-QlO is also capable of attenuating the intracellular deposition of Ap in transgenic AD mouse models. Additionally, the same group reported that Co-QlO administration also led to reduction of preexisting plaque burden in the same model. Such properties are suggestive of a potential therapeutic role for Co-QlO in AD. 

Most compounds oxidized by the electron transport chain donate hydrogen to NAD+, and then NADH is reoxidized in a reaction coupled to reduction of a flavoprotein. During this transformation, sufficient energy is released to enable synthesis of ATP from ADP. The reduced flavoprotein is reoxidized via reduction of coenzyme Q subsequent redox reactions then involve cytochromes and electron transfer processes rather than hydrogen transfer. In two of these cytochrome redox reactions, there is sufficient energy release to allow ATP synthesis. In... 

What has been achieved by the participation of coenzyme systems and the electron transport chain is twofold. First, there is no need for the substrate AH2 to react with oxygen. Second, it provides common routes for the oxidation of many different organic compounds, rather than a specific route for every compound, a vast variety of which will be present in... 

Figure 7-4. The electron transport chain. Electrons enter from NADH to complex I or succinate dehydrogenase, which is complex II. Electrons derived from glycolysis through the glycerol-3-phosphate shuttle, complex I, and complex II join at coenzyme Q and are transferred to oxygen as shown. As electrons pass through complexes I, III, and IV, protons are transported across the membrane, creating a pH gradient.

Recently introduced insecticide/acaricides, pyrimidifen and fenaza-quin (Figure 3.13), also inhibit the mitochondrial electron transport chain by binding with complex I at coenzyme site Q. 

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