title: Physiological Content and Intrinsic Activities of 10 Cytochrome P450 Isoforms in Human Normal Liver Microsomes.
abstract: Due to a lack of physiologic cytochrome P450 (P450) isoform content, P450 activity is typically only determined at the microsomal level (per milligram of microsomal protein) and not at the isoform level (per picomole of P450 isoform), which could result in the misunderstanding of variations in P450 activity between individuals and further hinder development of personalized medicine. We found that there were large variations in protein content, mRNA levels, and intrinsic activities of the 10 P450s in 100 human liver samples, in which CYP2E1 and CYP2C9 showed the highest expression levels. P450 gene polymorphisms had different effects on activity at two levels: CYP3A5*3 and CYP2A6*9 alleles conferred increased activity at the isoform level but decreased activity at the microsomal level; CYP2C9*3 had no effect at the isoform level but decreased activity at the microsomal level. The different effects at each level stem from the different effects of each polymorphism on the resulting P450 protein. Individuals with CYP2A6*1/*4, CYP2A6*1/*9, CYP2C9*1/*3, CYP2D6 100C>T TT, CYP2E1 7632T>A AA, CYP3A5*1*3, and CYP3A5*3*3 genotypes had significantly lower protein content, whereas CYP2D6 1661G>C mutants had a higher protein content. In conclusion, we first offered the physiologic data of 10 P450 isoform contents and found that some single nucleotide polymorphisms had obvious effects on P450 expression in human normal livers. The effects of gene polymorphisms on intrinsic P450 activity at the isoform level were quite different from those at the microsomal level, which might be due to changes in P450 protein content.
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Wei
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Yang-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.).
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Qian
authors.affiliation: Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, China (H.-F.Z., N.G., X.T., Y.F., J.Z., Q.W., J.G., H.-L.Q.); and State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China (H.-H.W., J.-Y.W., Y.-J.Z., Y.Z, X.-H.Q.) qiaohl@zzu.edu.cn 13911734119@163.com 13683167093@163.com.
authors.forename: Hai-Ling
authors.initials: HL
authors.lastname: Qiao
mesh_terms: D000367:Age Factors; D002853:Chromatography, Liquid; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D004364:Pharmaceutical Preparations; D020033:Protein Isoforms; D003577:Cytochrome P-450 Enzyme System