INTERSPECIES VARIATIONS IN CAFFEINE METABOLISM RELATED TO CYTOCHROME-P4501A ENZYMES

被引：111

作者：

BERTHOU, F

GUILLOIS, B

RICHE, C

DREANO, Y

JACQZAIGRAIN, E

BEAUNE, PH

机构：

[1] HOP NECKER ENFANTS MALAD,INSERM,U75,F-75730 PARIS 15,FRANCE

[2] HOP ROBERT DEBRE,PHARMACOL LAB,PARIS,FRANCE

来源：

XENOBIOTICA | 1992年 / 22卷 / 06期

关键词：

D O I：

10.3109/00498259209053129

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. Interspecies (including man, monkey, rabbit, rat and mouse) variations in caffeine metabolism by liver microsomes were studied. While N-3 demethylation was the major pathway in man (81% of total dimethylxanthines), N-7 demethylation was predominant in monkey (89%), and the three demethylation pathways were about equal in mouse, rabbit and rat. 2. Three monooxygenase activities (methoxyresorufin O-demethylase, phenacetin O-deethylase and acetanilide 4-hydroxylase) correlated significantly with the rate of metabolism of caffeine. 3. P4501A1 and 1A2 enzymes were immunodetected in different species. P4501A2 was the only isoform detected in liver of man, rat and mouse, while no polypeptide immunorelated to P4501A was detected in monkey and only a minor band of P4501A1 was detected in rat and rabbit. 4. All in vitro data indicate that paraxanthine formation is mediated mainly by P4501A2 in mammals while theophylline formation is mediated mainly by cytochromes P-450 other than those of the 1A family.

引用

页码：671 / 680

页数：10

共 36 条

[1] ARNAUD MJ, 1984, CAFFEINE PERSPECTIVE, P3
[2] EXPRESSION OF P1-450 AND P3-450 DNA CODING SEQUENCES AS ENZYMATICALLY ACTIVE CYTOCHROMES-P-450 IN MAMMALIAN-CELLS
BATTULA, N
SAGARA, J
GELBOIN, HV
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (12) : 4073 - 4077
[3] COMPARISON OF CAFFEINE METABOLISM BY SLICES, MICROSOMES AND HEPATOCYTE CULTURES FROM ADULT HUMAN-LIVER
BERTHOU, F
RATANASAVANH, D
RICHE, C
PICART, D
VOIRIN, T
GUILLOUZO, A
[J]. XENOBIOTICA, 1989, 19 (04) : 401 - 417
[4] BERTHOU F, 1991, DRUG METAB DISPOS, V19, P561
[5] CAFFEINE AND THEOPHYLLINE METABOLISM IN NEWBORN AND ADULT HUMAN HEPATOCYTES - COMPARISON WITH ADULT-RAT HEPATOCYTES
BERTHOU, F
RATANASAVANH, D
ALIX, D
CARLHANT, D
RICHE, C
GUILLOUZO, A
[J]. BIOCHEMICAL PHARMACOLOGY, 1988, 37 (19) : 3691 - 3700
[6] Bonati M., 1984, CAFFEINE PERSPECTIVE, P48
[7] SPECIES VARIATION IN THE RESPONSE OF THE CYTOCHROME P-450-DEPENDENT MONOOXYGENASE SYSTEM TO INDUCERS AND INHIBITORS
BOOBIS, AR
SESARDIC, D
MURRAY, BP
EDWARDS, RJ
SINGLETON, AM
RICH, KJ
MURRAY, S
DELATORRE, R
SEGURA, J
PELKONEN, O
PASANEN, M
KOBAYASHI, S
ZHIGUANG, T
DAVIES, DS
[J]. XENOBIOTICA, 1990, 20 (11) : 1139 - 1161
[8] HUMAN CYTOCHROME P-450PA (P-450IA2), THE PHENACETIN O-DEETHYLASE, IS PRIMARILY RESPONSIBLE FOR THE HEPATIC 3-DEMETHYLATION OF CAFFEINE AND N-OXIDATION OF CARCINOGENIC ARYLAMINES - (AROMATIC-AMINES HETEROCYCLIC AMINES CARCINOGEN METABOLISM)
BUTLER, MA
IWASAKI, M
GUENGERICH, FP
KADLUBAR, FF
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) : 7696 - 7700
[9] CAMPBELL ME, 1987, DRUG METAB DISPOS, V15, P237
[10] DISLERATH LM, 1985, J BIOL CHEM, V260, P9057

← 1 2 3 4 →