scholarly journals Cytochrome P450 2E1/2A6-Selective Inhibition by Halogenated Anilines on Metabolic Activation of Dimethylnitrosamine in Human Liver Microsomes

2006 ◽  
Vol 52 (5) ◽  
pp. 623-627 ◽  
Author(s):  
Yohei Ohashi ◽  
Taka-aki Kato ◽  
Katsuya Yamada ◽  
Takaharu Mizutani ◽  
Ken-ichi Saeki
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Metabolic Activation ◽  
Selective Inhibition ◽  
Human Liver Microsomes ◽  
Cytochrome P450 2E1

scholarly journals Exploring the Interactome of Cytochrome P450 2E1 in Human Liver Microsomes with Chemical Cross-Linking Mass Spectrometry

2021 ◽  
Author(s):  
Dmitri R. Davydov ◽  
Bikash Dangi ◽  
Guihua Yue ◽  
Bhagwat Prasad ◽  
Viktor G. Zgoda
Keyword(s):  
Mass Spectrometry ◽  
Cytochrome P450 ◽  
Protein Interactions ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cross Linking ◽  
Cytochrome P450 2E1 ◽  
Protein Protein Interactions ◽  
Chemical Cross Linking

This study aimed on exploration of the system-wide effects of the alcohol-induced increase in the content of cytochrome P450 2E1 (CYP2E1) in the human liver on drug metabolism. Using membrane incorporation of purified CYP2E1 modified with photoreactive crosslinkers benzophenone-4-maleimide (BPM) and 4-(N-succinimidylcarboxy)benzophenone (BPS), we explored the array of its protein-protein interactions (proteome) in human liver microsomes (HLM) with chemical cross-linking mass spectrometry (CXMS). Exposure of bait-incorporated HLM samples to light was followed by isolation of the His-tagged bait protein and its cross-linked aggregates on Ni-NTA agarose. Analyzing the individual bands of SDS-PAGE slabs of thereby isolated protein with the toolset of untargeted proteomics, we detected the cross-linked dimeric and trimeric complexes of CYP2E1 with other drug-metabolizing enzymes. Among the most extensively cross-linked partners of CYP2E1 are cytochromes P450 2A6, 3A4, 2C9, and 4A11. We also detected the conjugates of CYP2E1 with UDP-glucuronosyltransferases (UGTs) 1A6, 1A9, 2B4, 2B15, and 2B17. These results demonstrate the exploratory power of the proposed CXMS strategy and corroborate the concept of tight functional integration in the human drug-metabolizing ensemble through protein-protein interactions of the constituting enzymes. Of particular interest is the observation of efficient cross-linking of CYP2E1 with CYP4A11. This enzyme plays a central role in the synthesis of vasoactive eicosanoids and its interactions with alcohol-inducible CYP2E1 may shed light on the mechanisms of alcohol-induced hypertension.

Selective Inhibition of Cytochrome P450 2D6 by Sarpogrelate and Its Active Metabolite, M-1, in Human Liver Microsomes

2013 ◽  
Vol 42 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Doo-Yeoun Cho ◽  
Soo Hyeon Bae ◽  
Joeng Kee Lee ◽  
Yang Weon Kim ◽  
Bom-Taeck Kim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Metabolite ◽  
Human Liver ◽  
Liver Microsomes ◽  
Selective Inhibition ◽  
Human Liver Microsomes ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

Benzene metabolism by human liver microsomes in relation to cytochrome P450 2E1 activity

1994 ◽  
Vol 15 (9) ◽  
pp. 1799-1806 ◽  
Author(s):  
Mark J. Seaton ◽  
Paul M. Schlosser ◽  
James A. Bond ◽  
Michele A. Medinsky
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cytochrome P450 2E1
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