Quinone biotransformation reactions

Studies on metabolic stability using hepatocyte suspensions are not feasible for automation/HTS, but these studies do provide rather complete profiles of hepatic biotransformation without the supplements of cofactors and cosubstrates. The use of S9 in metabolic stability studies can be evaluated in a manner similar to that used for the microsomal assays, but with the possible addition of a broader panel of cofactors or cosubstrates. These include NADPH for CYP/FMO-mediated reactions, NADH for xanthine oxidoreductase and quinone oxidoreductase 2, NADPH-dependent reductions by carbonyl reductases, and NADPH/NADH-dependent reductions catalyzed by aldo-keto reductases, uridine 5 -diphosphate... 

The reductive biotransformation of drugs has been one of the least studied reactions, and many of the enzymes that are involved have not been well characterized. Some of the enzymes that catalyze reductive reactions of drugs are the cytochrome P450s, molybdenum reductases, alcohol dehydrogenases, carbonyl reductases, NADPH cytochrome P450 reductase, NAD(P)H— quinone oxidoreductases, and enzymes of the intestinal microflora (Matsunaga et al., 2006 Rosemond and Walsh, 2004). 

In extension to the above experiments the usefulness of the laccase/[G2]-PEG5k-[G2] complex for biotransformations of highly hydrophobic substrates is evaluated with BP and HBT. The reaction is followed by UV-Vis spectroscopy. Figure 7. It is seen that, despite the notable difference in the intensities, the spectral characteristics of reaction mixtures with BP (Figure 7A) are rather similar to those of mixtures without BP (Figure 7B). Obviously HBT is not spectroscopically suitable as mediator for the analysis of laccase mediated transformations of BP, since previous studies have shown that it can also be oxidized by laccase, and the reaction produces) possess absorption maxima in the same spectral region as the BP quinones (19, 20). 

The PAHs are substances capable of promoting several deleterious effects on organisms. The genotoxicity and mutagenicity of the PAHs can be established by different ways such as the adducts formation originated by the binding of their metabolites, resulted from the biotransformation via CYP with the DNA by the ROS production, from the quinone reaction, product of the PAHs metabolization via CYP, with the O2 among others. 

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