Cytochrome P450 reductase inhibition

Voznesensky, A.I. and Schenkman, J.B. (1992) Inhibition of cytochrome P450 reductase by polyols has an electrostatic nature. European Journal of Biochemistry, 210, 741—746. 

McGuire, J., Anderson, D. J., MacDonald, B. J., Narayanasami, R., Bennett, B. M., Inhibition of NADPH-cytochrome P450 reductase and glyceryl trinitrate biotransformation by diphenyleneiodonium sulfate. 

Marinello AJ, Berrigan MJ, Struck RF, et al. 1981. Inhibition of NADPH-Cytochrome P450 reductase by cylophosphamide and its metabolites. Biochem Biophys Res Commun 99 399-406. 

BPI has also been shown to inhibit cytochrome P450 reductase [156], Cohen, Gallop and coworkers demonstrated that DPI as well as the bis(2-thienyl)iodonium triflate inhibit superoxide anion formation in vivo in rabbit aorta [157]. It was proposed that the physiological activity of iodonium species is due to their... 

Zhang H, Hamdane D, Im SC, Waskell L (2008) Cytochrome b5 inhibits electron transfer from NADPH-cytochrome P450 reductase to ferric cytochrome P450 2B4. J Biol Chem 283 217-5225... 

Szczesna-Skorupa E, Kemper B (2011) Progesterone receptor membrane component 1 inhibits the activity of drug-metabolizing cytochromes P450 and binds to cytochrome P450 reductase. Mol Pharmacol 79 340-350... 

Transon C, Leemann T, Dayer P. In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1996 50(3) 209-215. 

In cell cultures, the expression of the reductase mRNA, like the tdc and stric-tosidine synthase sts) genes, was found to be induced by elicitors and down-regulated by auxins. GlOH was found to be localized in provacuolar membranes and not in the endoplasmic reticulum like many other cytochrome P450 enzymes. Interestingly, this enzyme is inhibited by the end product, alkaloid catharanthine, but not by vindoline and vinblastine. Therefore, feedback regulation may also operate in vivo, provided that the catharanthine and GlOH are within the same cellular compartment (Facchini and De Luca, 2008). 

Moreover, intracellular accumulation and cytochrome P450 catalyzed bioactivation of p-lactams such as cephaloridine overwhelms of the GSH redox cycle by inhibiting glutathione reductase activity [35, 56], depletion of GSH and accumulation of GSSG [35, 42, 49,56]. Most of GSSG formed is subsequently reduced by glutathione reductase and GSH is regenerated with concomitant oxidation (consumption) of NADPH to NADP+ [104]. 

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