Crystal Structures of Human Cytochrome P450 3A4 Bound to Metyrapone and Progesterone

Science ◽  
2004 ◽  
Vol 305 (5684) ◽  
pp. 683-686 ◽  
Author(s):  
P. A. Williams
1995 ◽  
Vol 270 (10) ◽  
pp. 5014-5018 ◽  
Author(s):  
Aditya P. Koley ◽  
Jeroen T. M. Buters ◽  
Richard C. Robinson ◽  
Allen Markowitz ◽  
Fred K. Friedman

ACS Omega ◽  
2021 ◽  
Author(s):  
Tunde L. Yusuf ◽  
Segun D. Oladipo ◽  
Sizwe Zamisa ◽  
Hezekiel M. Kumalo ◽  
Isiaka A. Lawal ◽  
...  

2011 ◽  
Vol 1 (1) ◽  
pp. 1 ◽  
Author(s):  
Marie Louise Hiort Hermann ◽  
Mette Tingleff Skaanild

Human cytochrome P450 3A7 (CYP3A7) and cytochrome P450 3A4 (CYP3A4) are hepatic metabolising enzymes which participates in the biotransformation of endo- and exogenous substances in foetuses and neonates respectively. These CYP3A enzymes display an inverse relationship: CYP3A7 is the dominant enzyme in the foetal liver, whereas the expression of CYP3A4 is low. After parturition there is a shift in the expression, thus CYP3A7 is down regulated, while the level of CYP3A4 gradually increases and becomes the dominant metabolising CYP3A enzyme in the adult. The minipig is increasingly being used as a model for humans in biomedical studies, because of its many similarities with the human physiology and anatomy. The aim of this study was to examine whether, as in humans, a shift is seen in the hepatic expression of a CYP3A7- like enzyme to cytochrome P450 3A29 (CYP3A29) (an orthologue to the human CYP3A4) in minipigs. This was elucidated by examining the hepatic mRNA expression of CYP3A7 and CYP3A29 in 39 foetuses and newborn Göttingen minipigs using quantitative real time polymerase chain reaction (qPCR). Furthermore the immunochemical level of CYP3A7-LE and CYP3A29 was measured in liver microsomes using western blotting. The expression of CYP3A29 was approximately 9- fold greater in neonates compared to foetuses, and a similar difference was reflected on the immunochemical level. It was not possible to detect a significant level of foetal CYP3A7 mRNA, but immunoblotting showed a visible difference depending on age. This study demonstrates an increase in the expression of CYP3A29, the CYP3A4 orthologue in perinatal minipigs as in humans, which suggests that the minipig could be a good model when testing for human foetal toxicity towards CYP3A4 substrates.


2017 ◽  
Vol 8 ◽  
Author(s):  
Danilo Degregorio ◽  
Serena D'Avino ◽  
Silvia Castrignanò ◽  
Giovanna Di Nardo ◽  
Sheila J. Sadeghi ◽  
...  

2010 ◽  
Vol 48 (1) ◽  
pp. 429-435 ◽  
Author(s):  
Yuka Kimura ◽  
Hideyuki Ito ◽  
Ryoko Ohnishi ◽  
Tsutomu Hatano

2020 ◽  
Vol 724 ◽  
pp. 138187
Author(s):  
Nai-Rong Liu ◽  
Kai Yang ◽  
Wen-Ting Li ◽  
Zhi-Hua Pang ◽  
Qing Zhang ◽  
...  

2006 ◽  
Vol 126 (3) ◽  
pp. 383-393 ◽  
Author(s):  
Nikolay P. Vasilev ◽  
Mattijs K. Julsing ◽  
Albert Koulman ◽  
Cailean Clarkson ◽  
Herman J. Woerdenbag ◽  
...  

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