Cytochrome oxidase activity induction

The kinetics of induction of cytochrome oxidase activity in Saccharo-myces carlsbergensis [99] can be seen to give an initially linear plot (Fig. 4). The oxidase appearing on induction exhibits the same K as... 

Fig. 4. Induction of cytochrome oxidase activity (as k second" per gram of protein per milliliter) in anaerobically grown, stationary-phase yeast cells. From Chen and Chara-lampous [99].

Saito et al. (134) found that the cytosolic nitroreductase activity was due to DT-diaphorase, aldehyde oxidase, xanthine oxidase plus other unidentified nitroreductases. As anticipated, the microsomal reduction of 1-nitropyrene was inhibited by 0 and stimulated by FMN which was attributed to this cofactor acting as an electron shuttle between NADPH-cytochrome P-450 reductase and cytochrome P-450. Carbon monoxide and type II cytochrome P-450 inhibitors decreased the rate of nitroreduction which was consistent with the involvement of cytochrome P-450. Induction of cytochromes P-450 increased rates of 1-aminopyrene formation and nitroreduction was demonstrated in a reconstituted cytochrome P-450 system, with isozyme P-448-IId catalyzing the reduction most efficiently. 

Disulfoton induced the liver MFO system in animals (Stevens et al. 1973). In the same study, exposure to disulfoton orally for 3 days also increased ethylmorphine N-demethylase and NADPH oxidase activities, but had no effect on NADPH cytochrome c reductase. Thus, the induction of the MFO system required repeated dosing with relatively high doses. Furthermore, these changes are not specific for disulfoton exposure, and these subtle liver effects require invasive techniques in humans to obtain liver tissue for performance of these enzyme assays. 

Melancon, M.J., C.R. Elcombe, M.J. Vodicnik and J.J. Lech. Induction of cytochromes P450 and mixed-function oxidase activity by polychlorinated biphenyls and beta-naphthoflavone in carp (Cyprinus carpio). Comp. Biochem. Physiol. 69C 219-226, 1981. 

While the hydroxylases of the adrenals and other steroid producing tissues show some (variable) catalytic activity towards xenobiotics (e.g., benzo[a]pyrene) (17) this is probably fortuitous in nature and it seems that, in general, the enzymes are quite specific for their respective steroid substrates. Furthermore, the steroid hydroxylases of the endocrine system are not susceptible to the inductive effects of xenobiotics as are the cytochrome P-450-mediated oxidases of the liver and other tissues (17,18) indeed, this is not unexpected, since if they responded to the external environment in this way their critical homeostatic role would rapidly be compromized. 

The experimental results given above clearly indicate that cytochrome P-450 is the oxygen-activating catalyst of a wide variety of mixed-function oxidations in tissues of vertebrate animals. Spectrophoto-metric measurements and determinations of the photochemical action spectra did not reveal any significant differences between the pigments from different sources. Yet the substrate specificity of these mixed-function oxidase systems is pronounced, as shown by studies on the induction of microsomal hydroxylase activity toward different xenobiotics (27) and on the affinity of different C-21 methyl corticosteroids toward... 

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