BIOTRANSFORMATION OF CAFFEINE, PARAXANTHINE, THEOBROMINE AND THEOPHYLLINE BY CDNA-EXPRESSED HUMAN CYP1A2 AND CYP2E1

被引：314

作者：

GU, L ^{[1
]}

GONZALEZ, FJ ^{[1
]}

KALOW, W ^{[1
]}

TANG, BK ^{[1
]}

机构：

[1] UNIV TORONTO,DEPT PHARMACOL,MED SCI BLDG,TORONTO M5S 1A8,ONTARIO,CANADA

来源：

PHARMACOGENETICS | 1992年 / 2卷 / 02期

关键词：

D O I：

10.1097/00008571-199204000-00004

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：73 / 77

页数：5

共 18 条

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