title: Expression of Bama Minipig and Human CYP3A Enzymes: Comparison of the Catalytic Characteristics with Each Other and Their Liver Microsomes.
abstract: Minipigs represent a good animal model because of the physiologic and anatomic similarities they share with humans. Three cytochrome P450 (CYP) 3A isozymes, CYP3A22, CYP3A29, and CYP3A46, have recently been reported to be expressed in Bama minipigs, which have limited data relating to their metabolic characteristics. In the present study, Bama minipig CYP3A22, CYP3A29, and CYP3A46 were recombinantly expressed and their metabolic manners were compared with those of human CYP3A4 and CYP3A5 and also human and Bama minipig liver microsomes. The results indicated Bama minipigs and human CYP3A enzymes showed similar metabolic kinetics and metabolite profiles using testosterone, midazolam, and nifedipine as substrates. However, the differences in amino acid sequences change the elimination velocity and metabolic preference of CYP3A enzymes to their substrates. It was demonstrated that CYP3A29, CYP3A4, and CYP3A5 were the most active enzymes for all reactions, whereas CYP3A46 was the least active enzyme. Substrate-dependent metabolism characteristics between human and Bama minipig CYP3A isoenzymes exist.
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Yicong
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Haitao
authors.initials: H
authors.lastname: Shang
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Lei
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Haihong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Kenan
authors.initials: K
authors.lastname: Guo
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Huidi
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.) yuls@zju.edu.cn weihong63528@163.com.
authors.forename: Lushan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.) yuls@zju.edu.cn weihong63528@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.affiliation: Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P.R. China (Y.B., Q.Y., J.L., H.H., H.J., L.Y., S.Z.); Clinical Pharmacology Research Laboratory, First Affiliated Hospital of Soochow University, Suzhou, P.R. China (Y.B.); and Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, P.R. China (H.S., K.G., H.W.).
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D000818:Animals; D055162:Biocatalysis; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology*; D061987:Sf9 Cells; D013552:Swine; D013556:Swine, Miniature
chemical_list: D051544:Cytochrome P-450 CYP3A