Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans

被引：59
|
作者：
Kitamura, S
Sugihara, K
Nakatani, K
Ohta, S
Oh-Hara, T
Ninomiya, S
Green, CE
Tyson, CA
机构：
[1] Hiroshima Univ, Sch Med, Inst Pharmaceut Sci, Minami Ku, Hiroshima 7348551, Japan
[2] Daiichi Pure Chem Co Ltd, ADME TOX Res Inst, Tokai, Ibaraki 3191182, Japan
[3] SRI Int, Menlo Park, CA 94025 USA
来源：
IUBMB LIFE | 1999年 / 48卷 / 06期
关键词：
aldehyde oxidase; cytosolic hydroxylase; human liver; 7-hydroxymethotrexate; interindividual variation; interspecies variation; methotrexate;
D O I：
10.1080/152165499306487
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
This study deals with individual and species variations in the converting activity of methotrexate (MTX) to 7-hydroxymethotrexate in animals acid humans. When MTX 7-hydroxylase was assayed in six human liver cytosols, a 38-fold range of intersubject variation of the activity was observed. The variations were correlated to the concentrations of aldehyde oxidase activity in human subjects assayed with benzaldehyde as a substrate, Species differences of Liver MTX 7-hydroxylase activity were also observed, The activity was highest in rabbits, followed by rats, hamsters, and monkeys but was undetectable in dogs. Strain differences of MTX 7-hydroxylase activity based on aldehyde oxidase activity were also observed in rats and mice. The results suggest that aldehyde oxidase functions as MTX: 7-hydroxylase in livers of animals and humans, and the observed differences of MTX 7-hydroxylase activity are due to variations in the amount of aldehyde oxidase present.
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页码：607 / 611
页数：5
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