Drug metabolism enzyme expression

Runge-Morris, M., Feng, Y, Zangar, R.C. Novak, R.F. (1996) Effects of hydrazine, phenelzine, and hydralazine treatment on rat hepatic and renal drug-metabolizing enzyme expression. DrugMetab. Disp., 24, 734-737... 

Lash, L.H., Putt, D.A., and Cai, H. (2008) Drug metabolism enzyme expression and activity in primary cultures of human proximal tubular cells. Toxicology 244, 56-65. 

From the above, it is clear that the gut wall represents more than just a physical barrier to oral drug absorption. In addition to the requirement to permeate the membrane of the enterocyte, the drug must avoid metabolism by the enzymes present in the gut wall cell as well as counter-absorptive efflux by transport proteins in the gut wall cell membrane. Metabolic enzymes expressed by the enterocyte include the cytochrome P450, glucuronyltransferases, sulfotransferases and esterases. The levels of expression of these enzymes in the small intestine can approach that of the liver. The most well-studied efflux transporter expressed by the enterocyte is P-gp. 

CYP3A is usually considered the most important of all drug-metabolizing enzymes as it accounts for nearly 40% of the total CYP enzymes expressed in the liver [15] and... 

The original humanized mice bear the expression hPXR exclusively in the liver [10]. As both drug-metabolizing enzymes and xenobiotic receptors are also highly expressed in the intestinal tracts, it is conceivable that mouse models with the humanized receptors expressed in both the liver and the intestine would represent a... 

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