Identification of Active Flavin-Containing Monooxygenase Isoform 2 in Human Lung and Characterization of Expressed Protein

• DOI: 10.1124/dmd.30.1.34
• Publication Date: 2003-01-16T00:26:29Z
• Authors: Sharon K. Krueger; Sarah R. Martin; Mei-Fei Yueh; Clifford B. Pereira; David E. Williams
• Keywords: Flavin-containing monooxygenase; Specific activity

Full-length human (hFMO2.1) and monkey (mFMO2) flavin-containing monooxygenase proteins, which share 97% sequence identity, were produced by baculovirus-mediated expression in insect cells assayed for <i>S</i>-oxygenation under conditions known to affect FMO activity. Both enzymes demonstrated maximal activity at pH 9.5; but hFMO2.1 retained significantly more than mFMO2 did 9.0 higher. also the presence of magnesium all detergents tested. Although had residual after heating 45°C mFMO2, some conditions, both less 10% control activity, whereas expressed rabbit FMO2 over 50% Screening NADPH-oxygenation hFMO2.1, indicated that substituted thioureas with a small cross-sectional area (2.4–4.3 Å) are good substrates, 1,3-diphenylthiourea (11.2 was not oxygenated. We confirmed lung tissue from heterozygous individual (<i>hFMO2*1</i>/<i>hFMO2*2A</i>) Western analysis <i>S</i>-oxygenation. These microsomes heat-associated loss similar hFMO2.1. The heat sensitivity may partially explain why post mortem samples has previously been unreported. Individuals have <i>FMO2*1</i>allele-encoding full-length exhibit altered drug metabolism lung.