Human Flavin-Containing Monooxygenase Form 2 S-Oxygenation: Sulfenic Acid Formation from Thioureas and Oxidation of Glutathione
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- 作者：Marilyn C. Henderson ; Sharon K. Krueger ; Jan F. Stevens ; and David E. Williams
- 刊名：Chemical Research in Toxicology
- 出版年：2004
- 出版时间：May 2004
- 年：2004
- 卷：17
- 期：5
- 页码：633 - 640
- 全文大小：167K
- 年卷期：v.17,no.5(May 2004)
- ISSN：1520-5010
文摘
Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming reactivesulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with GSH and drive oxidativestress 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% ofindividuals of African descent and 5% of Hispanics but not in Caucasians or Asians. We havepreviously demonstrated that human FMO2.1 protein expressed in Sf9 microsomes has highactivity toward a series of thioureas that are known or suspected lung toxicants includingthiourea, 1-phenylthiourea, and ethylenethiourea. We now show by HPLC and LC-MS that1-phenylthiourea and 
chars/alpha.gif" BORDER=0>-naphthylthiourea are converted to their sulfenic acids. GSH in theincubations at concentrations of 0.5-1.0 mM completely eliminated the sulfenic acid withresultant production of GSSG. These results indicate that individuals with the FMO2*1 allelemay be at enhanced risk of pulmonary damage upon exposure to thioureas.
chars/alpha.gif" BORDER=0>-naphthylthiourea are converted to their sulfenic acids. GSH in theincubations at concentrations of 0.5-1.0 mM completely eliminated the sulfenic acid withresultant production of GSSG. These results indicate that individuals with the FMO2*1 allelemay be at enhanced risk of pulmonary damage upon exposure to thioureas.