Cytochrome P450 irreversible

Minamiyama, Y., Takemura, S., Imaoka, S., Funae, Y., Tanimoto, Y., Inoue, M., Irreversible inhibition of cytochrome P450 by nitric oxide. J. Pharmacol. Exp. Then 283 (1997),... 

Aldehydes are oxidized to carboxylic acids. A major enzyme responsible for this oxidation is aldehyde dehydrogenase (see Aldehyde Dehydrogenases section in this chapter) (79) however, other enzymes such as AO and cytochromes P450 can also mediate the oxidation of aldehydes as discussed (discussed earlier in this chapter). Ketones are not substrates for aldehyde dehydrogenase for the same reason that tertiary alcohols cannot be oxidized by ALD. Unlike the oxidation of alcohols, the oxidation of aldehydes is irreversible. Aldehydes are usually toxic and therefore there are aldehyde dehydrogenases in virtually all cells and in most compartments within cells. 

Cytochrome P450 3A4-mediated bioactivation of raloxifene irreversible... 

Irreversible Cytochrome P450 Inhibition Common Substructures and Implications for Drug Development... 

Human liver preparations metabolize ethylene dibromide to water-soluble and irreversibly protein- and DNA-bound metabolites by both cytochrome P450 and glutathione S-transferase (GST) enzymes (Wiersma et al., 1986). DNA adduct formation occurs also in isolated human hepatocytes (Cmarik et al., 1990). 

In rats, the conversion of vinyl bromide to reactive metabolites occurs primarily in hepatocytes. Irreversible binding of such metabolites to proteins and RNA has been established both with rat-liver microsomes in vitro and in rats in vivo. They can also alkylate the cytochrome P450 prosthetic group of phenobarbital-treated rat-liver microsomes. Exposure of rats to vinyl bromide causes a decrease in hepatic cytochrome P450 (lARC, 1986). 

Testing for the cytochrome P450 liver enzyme really created a lot of understanding. The DNA test results were explained in a very clear way by an environmental health specialist, and it made us realize that my situation was inborn and irreversible, and that we had to learn to live with it. My various ailments — which over the years had been given all sorts of names — all really fell into place after the DNA test results. It was important for me to consistently avoid chemical substances and to try to detoxify as much as possible in order to achieve improvement and prevent eventual organ damage. 

Chen Q, Ngui JS, Doss GA, et al. Cytochrome P450 3A4-mediated bioactivation of raloxifene irreversible enzyme inhibition and thiol adduct formation. Chem Res Toxicol 2002 15(7) 907-914. 

The second type of drug inhibition results from irreversible (or quasi-irreversible ) inhibition of cytochrome P450 and often involves metabolism-dependent inhibition or suicide inactivation of cytochrome P450 (Ortiz de Montellano 1995). 

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