Kobayashi K, Abe S, Nakajima M, Shimada N, Tani M, Chiba K, Yamamoto T
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Drug Metab Dispos. 1999 Dec;27(12):1429-33.
The role of cytochrome P-450s (CYPs) in S-mephobarbital N-demethylation was investigated by using human liver microsomes and cDNA-expressed CYPs. Among the 10 cDNA-expressed CYPs studied (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), only CYP2B6 could catalyze S-mephobarbital N-demethylation. The apparent K(m) values of human liver microsomes for S-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 microM). The N-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920, p<.001). Orphenadrine (300 microM), a CYP2B6 inhibitor, inhibited the N-demethylase activity of S-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzes S-mephobarbital N-demethylation in human liver microsomes.
利用人肝微粒体和cDNA表达的细胞色素P-450（CYPs）研究了CYPs在S-美芬妥英N-脱甲基反应中的作用。在所研究的10种cDNA表达的CYPs（CYP1A1、CYP1A2、CYP2A6、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP2E1和CYP3A4）中，只有CYP2B6能够催化S-美芬妥英N-脱甲基反应。人肝微粒体对S-美芬妥英N-脱甲基反应的表观K(m)值与cDNA表达的CYP2B6的表观K(m)值相近（约250 microM）。10个人肝微粒体中S-美芬妥英的N-脱甲基酶活性与免疫可检测的CYP2B6水平密切相关（r = 0.920，p<0.001）。CYP2B6抑制剂邻甲苯海明（300 microM）将人肝微粒体中S-美芬妥英的N-脱甲基酶活性抑制至对照活性的29%。因此，似乎CYP2B6主要催化人肝微粒体中S-美芬妥英的N-脱甲基反应。
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