Quantification of Flavin-containing Monooxygenases 1, 3, and 5 in Human Liver Microsomes by UPLC-MRM-Based Targeted Quantitative Proteomics and Its Application to the Study of Ontogeny

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Yao ChenMichael Zhuo Wang

Abstract

Flavin-containing monooxygenases (FMOs) have a significant role in the metabolism of small molecule pharmaceuticals. Among the five human FMOs, FMO1, FMO3, and FMO5 are the most relevant to hepatic drug metabolism. Although age-dependent hepatic protein expression, based on immunoquantification, has been reported previously for FMO1 and FMO3, there is very little information on hepatic FMO5 protein expression. To overcome the limitations of immunoquantification, an ultra-performance liquid chromatography (UPLC)-multiple reaction monitoring (MRM)-based targeted quantitative proteomic method was developed and optimized for the quantification of FMO1, FMO3, and FMO5 in human liver microsomes (HLM). A post-in silico product ion screening process was incorporated to verify LC-MRM detection of potential signature peptides before their synthesis. The developed method was validated by correlating marker substrate activity and protein expression in a panel of adult individual donor HLM (age 39-67 years). The mean (range) protein expression of FMO3 and FMO5 was 46 (26-65) pmol/mg HLM protein and 27 (11.5-49) pmol/mg HLM protein, respectively. To demonstrate quantification of FMO1, a panel of fetal individual donor HLM (gestational age 14...Continue Reading

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Oct 21, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Souzan B YanniDhiren R Thakker
May 13, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Scott Michaels, Michael Zhuo Wang
May 1, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kuan-wei PengMichael Zhuo Wang

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Citations

Jun 16, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Steven Leeder, Bernd Meibohm
Jun 15, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robert S Foti, Deepak K Dalvie
Aug 19, 2017·The Journal of Pharmacology and Experimental Therapeutics·Meijuan XuBhagwat Prasad
Dec 2, 2020·Expert Opinion on Drug Metabolism & Toxicology·Siavosh Naji-TalakarBhagwat Prasad
Dec 29, 2020·Frontiers in Genetics·Beatriz Carvalho HenriquesKatherine J Aitchison

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