Cytochrome antioxidants

FIGURE 17.3 Scheme of the detection principle of antioxidant activity using a cytochrome c functionalized gold electrode. A0I is the antioxidant under investigation. (From [213], with permission.)... 

Skulachev [117] proposed that the released cytochrome c oxidizes superoxide and, by this, exhibits an antioxidant function. This proposal was supported by recent experimental findings by Atlante et al. [118], who suggested that cytochrome c released from mitochondria by oxygen species protected mitochondria through a feedback-like process oxidizing superoxide. The most important physiological inhibitor of apoptosis is multifunctional protein Bcl-2,... 

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

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 administration of Qio or quercetin to rats protected against endotoxin-induced shock in rat brain [252]. It was found that the pretreatment with these antioxidants diminished the shock-induced increase in brain MDA and nitric oxide levels. Interesting data have been obtained by Yamamura et al. [253] who showed that ubiquinone Qi0 is able to play a double role in mitochondria. It was found that on the one hand, Q10 enhanced the release of hydrogen peroxide from antimycin A- or calcium-treated mitochondria, but on the other hand, it inhibited mitochondrial lipid peroxidation. It was proposed that Q10 acts as a prooxidant participating in redox signaling and as an antioxidant suppressing permeability transition and cytochrome c release. 

Similar to some other antioxidants, pyrrolopyrimidines do not contain active free radical scavenging groups such as phenolic or thiolic substituents. At present, at least two different mechanisms of their antioxidant activity have been proposed [307], It was suggested that pyrrolopyrimidines, which are electron donating compounds, can be oxidized by hydroxyl or peroxyl radicals or hydroxylated by cytochrome P-450 forming phenolic metabolite... 

Fouchecourt, M.O. and J.L. Riviere. 1995. Activities of cytochrome P450-dependent monooxygenases and antioxidant enzymes in different organs of Norway rats (Rattus norvegicus) inhabiting reference and contaminated sites. Chemosphere 3L4375A386. 

Witte P, Beuerle F, Hartnagel U, Lebovitz R, Savouchkina A, Sali S, Guldi D, Chionakis N, Hirsch A (2007) Water-solubility, antioxidant activity and cytochrome C binding of four families of exohedral adducts of C60 and C7Q. Org. Biomol. Chem. 5 3599-3613. 

The synthesis of ROS can be catalyzed by iron ions, for example. Reaction of O2 with FMN or FAD (see p. 32) also constantly produces ROS. By contrast, reduction of O2 by cytochrome c-oxidase (see p. 140) is clean, as the enzyme does not release the intermediates. In addition to antioxidants (B), enzymes also provide protection against ROS superoxide dismutase [1] breaks down ( dispropor-tionates ) two superoxide molecules into O2 and the less damaging H2O2. The latter is in turn disproportionated into O2 and H2O by heme-containing catalase [2]. 

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