咖啡因、副黄嘌呤、可可碱和茶碱经cDNA表达的人CYP1A2和CYP2E1的生物转化作用

Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1.

作者信息

Gu L, Gonzalez F J, Kalow W, Tang B K

机构信息

Department of Pharmacology, University of Toronto, Canada.

出版信息

Pharmacogenetics. 1992 Apr;2(2):73-7. doi: 10.1097/00008571-199204000-00004.

DOI:10.1097/00008571-199204000-00004

PMID:1302044

Abstract

Six human cytochrome P450s expressed in HepG2 cells using vaccinia virus cDNA-directed expression, were used to study the biotransformation of caffeine and its metabolites. CYP1A2 alone was responsible for caffeine 3-demethylation and paraxanthine 7-demethylation; in addition, 1A2 catalysed virtually all reactions related to caffeine and its metabolites. The metabolic profile of caffeine biotransformation by CYP1A2 averaged 81.5% for paraxanthine, 10.8% for theobromine and 5.4% for theophylline formation. It remained quite uniform when caffeine concentrations were varied. The most striking finding was that CYP2E1 (the ethanol-inducible form) had major influences upon caffeine metabolism: in particular, it catalysed the formation of theophylline and theobromine from caffeine. Thus, the in vivo metabolite profiling of caffeine may reveal CYP2E1 activities in addition to the previously documented activities of CYP1A2, polymorphic N-acetyltransferase and xanthine oxidase.

摘要

利用痘苗病毒cDNA定向表达在HepG2细胞中表达的六种人细胞色素P450，用于研究咖啡因及其代谢物的生物转化。仅CYP1A2负责咖啡因的3-去甲基化和副黄嘌呤的7-去甲基化；此外，1A2催化了几乎所有与咖啡因及其代谢物相关的反应。CYP1A2对咖啡因生物转化的代谢谱平均为：副黄嘌呤形成占81.5%，可可碱形成占10.8%，茶碱形成占5.4%。当咖啡因浓度变化时，其代谢谱保持相当一致。最显著的发现是CYP2E1（乙醇诱导型）对咖啡因代谢有重大影响：特别是，它催化咖啡因形成茶碱和可可碱。因此，咖啡因的体内代谢物谱分析除了可揭示先前记录的CYP1A2、多态性N-乙酰转移酶和黄嘌呤氧化酶的活性外，还可能揭示CYP2E1的活性。