Journal of the Mass Spectrometry Society of Japan
Online ISSN : 1880-4225
Print ISSN : 1340-8097
ISSN-L : 1340-8097
REVIEW
Application of Deuterium Isotope Effects to the Xenobiotic Metabolism Study
Norio KURIHARA
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1998 Volume 46 Issue 3 Pages 157-172

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Abstract
Deuterium substitution of certain hydrogen atoms in a molecule may change its metabolism rate in various biological systems. Some of the deuterium labeled pesticides were metabolized in some in vitro systems, such as rat liver microsomes and purified P450 reconstituted systems, in a slower rate than the unlabeled counterpart. This sometimes caused a substantial bioactivity-insecticidal activity, etc.-enhancement. Metabolic reactions of lindane, DDT analogs, diuron analogs and methoxychlor are discussed. Measurement of isotope effect values would provide us various information on the biological and biochemical reactions. There are examples of metabolic reaction mechanism studies of oxidative O-demethylations of methoxy-compounds, oxidative N-demethylations of N-methylamine derivatives and benzene ring hydroxylations using specifically deuteriated aromatic compounds. These studies revealed some details of relevant metabolic reaction pathways, the information that cannot be obtained by other methods. Analysis of very large isotope effect values observed in some metabolic reactions of xenobiotics, such as indene derivatives, revealed a branched metabolic pathway. Also, a tunnel effect in metabolic reactions was proposed for some xenobiotic metabolism that exhibited a very large observed isotope effect value, for example metabolic oxygenation of linoleic acid and methane. Mass spectrometric analysis is an essential means in all these studies.
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© 1998 by The Mass Spectrometry Society of Japan
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