Comparison of the substrate kinetics of pig CYP3A29 with pig liver microsomes and human CYP3A4

Abstract

CYP (cytochrome P450) 3A29 in pigs could be an important candidate gene responsible for xenobiotic metabolism, similar to CYP3A4 in humans. Accordingly, the tissue expression of CYP3A29 mRNA in domestic pigs has been determined by a real-time PCR. The enzymatic properties of CYP3A29, CYP3A4 and PLM (pig liver microsomes) were compared by kinetic analysis of TST (testosterone) 6β-hydroxylation and NIF (nifedipine) oxidation. CYP3A29 mRNA was highly expressed in the liver and small intestines of domestic pigs. The CYP3A29 enzyme expressed in Sf9 cells had the same TST-metabolizing activity as human CYP3A4 based on their roughly equal in vitro intrinsic clearance values. The affinity of CYP3A29 for NIF was lower than that of CYP3A4 but higher than that of PLM. KET (ketoconazole) was a more potent inhibitor of TST 6β-hydroxylation and NIF oxidation activities of CYP3A29 than TAO (troleandomycin). These findings indicate that pig CYP3A29 is similar to human CYP3A4 in both extent of expression and activity. The results reported in this paper provide a basis for future in vitro toxicity and metabolism studies.