Enzymatic oxidation of xenobiotic chemicals
Abstract
Studies with biomimetic models can yield considerable insight into mechanisms of enzymatic catalysis. The discussion above indicates how such information has been important in the cases of flavoproteins, hemoproteins, and, to a lesser extent, the copper protein dopamine beta-hydroxylase. Some of the moieties that we generally accept as intermediates (i.e., high-valent iron oxygen complex in cytochrome P-450 reactions) would be extremely hard to characterize were it not for biomimetic models and more stable analogs such as peroxidase Compound I complexes. Although biomimetic models can be useful, we do need to keep them in perspective. It is possible to alter ligands and aspects of the environment in a way that may not reflect the active site of the protein. Eventually, the model work needs to be carried back to the proteins. We have seen that diagnostic substrates can be of considerable use in understanding enzymes and examples of elucidation of mechanisms through the use of rearrangements, mechanism-based inactivation, isotope labeling, kinetic isotope effects, and free energy relationships have been given. The point should be made that a myriad of approaches need to be applied to the study of each enzyme, for there is potenti...Continue Reading
References
Citations
Characterisation of praziquantel metabolism by rat liver microsomes using cytochrome P450 inhibitors
Induction of CYP isoenzymes in various organs of rats by 3-methylcholanthrene or beta-naphthoflavone
P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues
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