Mitochondrial Electron Transport Chains

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. 

FIGURE 21.3 % J and % values for the components of the mitochondrial electron transport chain. Values indicated are consensus values for animal mitochondria. Black bars represent %r red bars,. ... 

The Stoichiometry of Proton Pumping by the Mitochondrial Electron-Transport Chain 129... 

Complexes of the Mitochondrial Electron-Transport Chain Complex I (NADH Ubiquinone Oxidoreductase)... 

Polymorphonuclear leucocytes (PMNs) employ a system comprising myeloperoxidase, hydrogen peroxide, and a halide factor to kill microorganisms and tumour cells. This process is sometimes loosely called the respiratory burst , which refers to the sudden rise in oxygen consumption by the phagocytosing neutrophils that is independent of the mitochondrial 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). 

FIGURE 32-7 Sources of free radical formation which may contribute to injury during ischemia-reperfusion. Nitric oxide synthase, the mitochondrial electron-transport chain and metabolism of arachidonic acid are among the likely contributors. CaM, calcium/calmodulin FAD, flavin adenine dinucleotide FMN, flavin mononucleotide HtT, tetrahydrobiopterin HETES, hydroxyeicosatetraenoic acids L, lipid alkoxyl radical LOO, lipid peroxyl radical NO, nitric oxide 0 "2, superoxide radical. 

Figure 5.17 The mitochondrial electron-transport chain. (From Voet and Voet, 2004. Reproduced with permission from John Wiley Sons., Inc.)...

NADH reoxidized by mitochondrial electron transport chain... 

Iron is also a key constitnent of many enzymes involved in electron transfer reactions, inclnding those involved in the mitochondrial electron transport chain conpled to the synthesis of ATP. 

Mitochondria have their own limited genome, the remnants of the genome of the microorganism from which they are derived. Mitochondrial genes code for 13 proteins that are synthesized in the mitochondria and are critical parts of the mitochondrial electron transport chain. 

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. 

Electrons are removed from NADH and delivered to the mitochondrial electron transport chain where they ultimately are transferred to oxygen (see Chapter 7). 

Furthermore, Marshall et al. developed the extractable MBF tracer 7 -[ F] fluoro-6, 7 -dihydrorotenone (p F]FDHR) [72]. p F]FDHR is a derivative of the neutral and lipophilic lead compound rotenone that binds to the complex I of the mitochondrial electron transport chain [73-76]. It was prepared from 7 -tosyl-oxy-6, 7 -dihydroroten-12-ol (DHR-ol-OTos) in two steps. After nucleophilic substitution of DHR-ol-OTos with p F]fluoride, the intermediate was oxidized with manganese dioxide to yield the target compound [ F]FDHR (Fig. 11). 

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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