Role of human glutathione-S-transferases in the inactivation of reactive metabolites of clozapine Adapted from: Role of human glutathione-S-transferases in the inactivation of reactive metabolites of clozapine
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Reconstitution of the interplay between cytochrome P450 and human glutathione S-transferases in clozapine metabolism in yeast.
Clozapine, an often-prescribed antipsychotic drug, is implicated in severe adverse drug reactions (ADRs). Formation of reactive intermediates by cytochrome P450s (CYPs) has been proposed as a possible explanation for these ADRs. Moreover, a protective role for human glutathione S-transferases (hGSTs) was recently shown using purified enzymes. We investigated the interplay between CYP bioactivat...
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Resistance of the weanling rat to acetaminophen (AP AP)-induced hepatotoxicity is manifested with regard to a surge in APAP-glutathione (OSH) conjugate formation in the liver [Allameh et al. Mech Aging Dev 95(1997)71]. The present study was conducted to assess the role of this detoxification pathway in APAPinduced lipid per6xidationin the liver. Lipid peroxidation measured as thiobarbituric...
متن کاملRole of Residue 87 in the Activity and Regioselectivity of Clozapine Metabolism by Drug Metabolizing Bm3 M11: Application for Structural Characterization of Clozapine Gsh Conjugates
In the present study, a site-saturation mutagenesis library of drug metabolizing BM3 M11 with all 20 amino acids at position 87 was applied as biocatalyst for the production of stable and reactive metabolites of clozapine. Clozapine is an atypical antipsychotic drug where formation of reactive metabolites is considered to be responsible for several adverse drug reactions. Reactive intermediates...
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Class-Pi of glutathione s-transferases (GST-Pi) is the specific form of GSTs that are known to participate particularly in the mechanisms of resistance to drugs and carcinogens. This class of the enzyme is referred to as class-P or class-Pi or class π. The accepted terminology in this review article is class-Pi. In this article following a brief description of identified molecular forms of GSTs...
متن کاملRole of residue 87 in the activity and regioselectivity of clozapine metabolism by drug-metabolizing CYP102A1 M11H: application for structural characterization of clozapine GSH conjugates.
In the present study, a site-saturation mutagenesis library of drug-metabolizing CYP102A1 M11H with all 20 amino acids at position 87 was applied as a biocatalyst for the production of stable and reactive metabolites of clozapine. Clozapine is an atypical antipsychotic drug in which formation of reactive metabolites is considered to be responsible for several adverse drug reactions. Reactive in...
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تاریخ انتشار 2013