Nicotine-N'-Oxidation by Flavin Monooxygenase Enzymes.

ABSTRACT:

Background

The major mode of metabolism of nicotine is by hydroxylation via cytochrome P450 (CYP) 2A6, but it can also undergo glucuronidation by UDP-glucuronosyltransferases and oxidation by flavin monooxygenases (FMO). The goal of this study was to examine the potential importance of FMOs in nicotine metabolism and assess the potential impact of missense polymorphisms in active FMOs on nicotine-N'-oxide (NOX) formation.

Methods

Urine samples from 106 current Chinese smokers were analyzed for nicotine metabolites by mass spectrometry. Wild-type FMOs 1-5 and their most prevalent nonsynonymous variants were cloned and overexpressed in HEK293 cells, and were tested in oxidation reactions against nicotine.

Results

A strong inverse correlation was observed b

SUBMITTER: Perez-Paramo YX 

PROVIDER: S-EPMC6363832 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature