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Variation of Hepatic Methotrexate 7‐Hydroxylase Activity in Animals and Humans
Author(s) -
Kitamura Shigeyuki,
Sugihara Kazumi,
Nakatani Keiko,
Ohta Shigeru,
OhHara Toshinari,
Ninomiya ShinIchi,
Green Carol E.,
Tyson Charles A.
Publication year - 1999
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/713803569
Subject(s) - aldehyde oxidase , chemistry , enzyme , biochemistry , specific activity , oxidase test , methotrexate , endocrinology , medicine , pharmacology , biology , xanthine oxidase
This study deals with individual and species variations in the converting activity of methotrexate (MTX) to 7‐hydroxymethotrexate in animals and humans. When MTX 7‐hydroxylase was assayed in six human liver cytosols, a 48‐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.