Oxidation of nonionic detergents by cytochrome P450 enzymes.

Hosea NA, Guengerich FP
Arch Biochem Biophys. 1998 353 (2): 365-73

PMID: 9606971 · DOI:10.1006/abbi.1998.0659

Nonionic phenolic detergents are commonly used in the purification of membrane-associated proteins. Triton N-101 was shown to be oxidized by NADPH-fortified human liver microsomes and recombinant human cytochromes P450 (P450). Oxidation was monitored using HPLC and the fluorescence properties of Triton N-101 and other alkylphenol ethoxylate detergents, which are similar to those of anisole. Human liver microsomes and recombinantly expressed reconstituted P450 3A4-oxidized Triton N-101 in a concentration-dependent manner which could be inhibited by ketoconazole, a P450 3A4-selective inhibitor. Triton N-101 inhibition of testosterone oxidation by human liver microsomes was of a mixed nature but mainly non-competitive. Electrospray ionization mass spectrometry and tandem mass spectrometry indicated that the major product formed was hydroxylated on the alkyl moiety. Human liver microsomes also oxidized other Tritons (X-100 and X-114), Emulgens 911 and 913, and Tergitol NP-10 to a similar extent. P450s 1A1, 1A2, and 2C9 also oxidized Triton N-101 but to a lesser extent than P450 3A4. We conclude that Triton N-101 and similar nonionic detergents are oxidized by P450 3A4 and some other P450s.

MeSH Terms (16)

Catalysis Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System Detergents Humans In Vitro Techniques Microsomes, Liver Mixed Function Oxygenases Nonoxynol Octoxynol Oxidation-Reduction Poloxalene Polyethylene Glycols Spectrometry, Fluorescence Spectrophotometry, Atomic Testosterone

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