Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin-containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined t...

The metabolism of dipropyl disulfide (DPDS), an Allium sulfur compound, was investigated in rat liver cell subfractions and in an isolated perfused rat liver. DPDS is oxidized to dipropyl thiosulfinate (DPDSO) by rat microsomes. The contribution of cytochrome P450 enzymes (CYPs) or flavin-containing monooxygenases (FMO) to the formation of DPDSO from its precursor was investigated. In rat micro...

Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming reactive sulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with GSH and drive oxidative stress through a redox cycle. For this reason, thiourea S-oxygenation is an example of FMO-dependent bioactivation of a xenobiotic. Functional FMO2 is expressed in the lung of 26% of individuals of African descent ...

10-Chloromethyl-11-demethyl-12-oxo-calanolide (F18), an analog of calanolide A, is a novel potent nonnucleoside reverse transcriptase inhibitor against HIV-1. Here, we report the metabolic profile and the results of associated biochemical studies of F18 in vitro and in vivo. The metabolites of F18 were identified based on liquid chromatography-electrospray ionization mass spectrometry and/or nu...

Multiple drug resistance (MDR) in Mycobacterium tuberculosis (mTB), the causative agent for tuberculosis (TB), has led to increased use of second-line drugs, including ethionamide (ETA). ETA is a prodrug bioactivated by mycobacterial and mammalian flavin-containing monooxygenases (FMOs). FMO2 is the major isoform in the lungs of most mammals, including primates. In humans a polymorphism exists ...

The flavin-containing monooxygenases (FMOs) are a family of five microsomal enzymes important for the oxidative metabolism of environmental toxicants, natural products, and therapeutics. With the exception of FMO5, the FMO are encoded within a single gene cluster on human chromosome 1q23-25. As part of the human genome effort, an FMO-like gene, FMO6, was identified between FMO3 and FMO2 (GenBan...

Multiple drug resistance (MDR) in Mycobacterium tuberculosis (mTB), the causative agent for tuberculosis (TB), has led to increased use of second-line drugs, including ethionamide (ETA). ETA is a prodrug bioactivated by mycobacterial and mammalian flavin-containing monooxygenases (FMOs). FMO2 is the major isoform in the lungs of most mammals, including primates. In humans a polymorphism exists ...

We have studied the intriguing gas-phase dimerization of the B12In(-) (n = 9, 8) anions to B24I2n(2-) dianions by means of density functional theory calculations. The dimerization of B12I9(-) to B24I18(2-) has been detected experimentally in a previous study (Phys. Chem. Chem. Phys., 2011, 13, 5712) utilizing electrospray ionization ion trap mass spectrometry (ESI-IT-MS), whereas the formation ...

Incubations with human liver and gut microsomes revealed that the antibiotic, clindamycin, is primarily oxidized to form clindamycin sulfoxide. In this report, evidence is presented that the S-oxidation of clindamycin is primarily mediated by CYP3A. This conclusion is based upon several lines of in vitro evidence, including the following. 1) Incubations with clindamycin in hepatic microsomes fr...

The expression of flavin-containing monooxygenases (FMOs) in dog liver microsomes was suggested by a high methimazole S-oxidase activity. When the reaction was catalyzed by dog liver microsomes, apparent V(max) and K(m) values were 6.3 nmol/min/mg and 14 microM, respectively. This reaction was highly inhibited (73%) in the presence of imipramine, but it was also weakly affected by trimethylamin...