Premium
Kinetic isotope effects and ‘metabolic switching’ in cytochrome P450‐catalyzed reactions
Author(s) -
Miwa Gerald T.,
Lu Anthony Y. H.
Publication year - 1987
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.950070506
Subject(s) - kinetic isotope effect , substrate (aquarium) , enzyme , chemistry , cytochrome p450 , catalysis , metabolism , active site , stereochemistry , kinetic energy , metabolic pathway , isotope , cytochrome , biochemistry , biology , physics , ecology , deuterium , quantum mechanics
Abstract The mechanistic significance of a kinetic isotope effect on a cytochrome P‐450catalyzed reaction depends, fundamentally, on the nature of the interaction of the substrate with the active site of the enzyme as well as on the nature of the chemistry of the reaction catalyzed. Consequently, kinetic isotope effects can be used to extract information on the topology of the enzyme and the mechanism of substrate oxidation. Kinetic isotope effect studies are sometimes accompanied by ‘metabolic switching’ or a change in metabolic pathway, catalyzed either by the same enzyme or by a different enzyme. For the specific case where ‘metabolic switching’ gives rise to a change in regional specificity for the cytochrome P‐450 catalyzed metabolism of a compound, this change can be explained in terms of the topological constraints on substrate binding imposed by the active site of the enzyme.