Effect of Human Glutathione S-Transferases on Glutathione-Dependent Inactivation of Cytochrome P450-Dependent Reactive Intermediates of Diclofenac

2013 ◽  
Vol 26 (11) ◽  
pp. 1632-1641 ◽  
Author(s):  
Sanja Dragovic ◽  
Jan Simon Boerma ◽  
Nico P. E. Vermeulen ◽  
Jan N. M. Commandeur
Keyword(s):  
Cytochrome P450 ◽  
Reactive Intermediates ◽  
Dependent Inactivation ◽  
Glutathione S Transferases

Differential Time-Dependent Inactivation of P450 3A4 and P450 3A5 by Raloxifene: A Key Role for C239 in Quenching Reactive Intermediates

2007 ◽  
Vol 20 (12) ◽  
pp. 1778-1786 ◽  
Author(s):  
Josh T. Pearson ◽  
Jan L. Wahlstrom ◽  
Leslie J. Dickmann ◽  
Santosh Kumar ◽  
James R. Halpert ◽  
...  
Keyword(s):  
Reactive Intermediates ◽  
Time Dependent ◽  
Dependent Inactivation

scholarly journals Cytochrome P450 enzymes: understanding the biochemical hieroglyphs

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 178 ◽  
Author(s):  
John T. Groves
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Reactive Intermediates ◽  
Heme Iron ◽  
Cytochrome P450 Enzymes ◽  
Steroid Biosynthesis ◽  
Reaction Cycle ◽  
Cyp Enzymes ◽  
Protein Architecture ◽  
Recent Advances

Cytochrome P450 (CYP) enzymes are the primary proteins of drug metabolism and steroid biosynthesis. These crucial proteins have long been known to harbor a cysteine thiolate bound to the heme iron. Recent advances in the field have illuminated the nature of reactive intermediates in the reaction cycle. Similar intermediates have been observed and characterized in novel heme-thiolate proteins of fungal origin. Insights from these discoveries have begun to solve the riddle of how enzyme biocatalyst design can afford a protein that can transform substrates that are more difficult to oxidize than the surrounding protein architecture.

scholarly journals Monitoring Insecticide Susceptibility in Aedes Aegypti Populations from the Two Biggest Cities, Ouagadougou and Bobo-Dioulasso, in Burkina Faso: Implication of Metabolic Resistance

2020 ◽  
Vol 5 (2) ◽  
pp. 84
Author(s):  
Moussa Namountougou ◽  
Dieudonné Diloma Soma ◽  
Mahamoudou Balboné ◽  
Didier Alexandre Kaboré ◽  
Mahamadi Kientega ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Aedes Aegypti ◽  
West Africa ◽  
Insecticide Resistance ◽  
Burkina Faso ◽  
Urban Areas ◽  
Mortality Rates ◽  
Metabolic Resistance ◽  
Bobo Dioulasso ◽  
Glutathione S Transferases

In West Africa, Aedes aegypti remains the major vector of dengue virus. Since 2013, dengue fever has been reemerging in Burkina Faso with annual outbreaks, thus becoming a major public health problem. Its control relies on vector control, which is unfortunately facing the problem of insecticide resistance. At the time of this study, although data on phenotypic resistance were available, information related to the metabolic resistance in Aedes populations from Burkina Faso remained very scarce. Here, we assessed the phenotypic and the metabolic resistance of Ae. aegypti populations sampled from the two main urban areas (Ouagadougou and Bobo-Dioulasso) of Burkina Faso. Insecticide susceptibility bioassays to chlorpyriphos-methyl 0.4%, bendiocarb 0.1% and deltamethrin 0.05% were performed on natural populations of Ae. aegypti using the WHO protocol. The activity of enzymes involved in the rapid detoxification of insecticides, especially non-specific esterases, oxidases (cytochrome P450) and glutathione-S-transferases, was measured on individual mosquitos. The mortality rates for deltamethrin 0.05% were low and ranged from 20.72% to 89.62% in the Bobo-Dioulasso and Ouagadougou sites, respectively. When bendiocarb 0.1% was tested, the mortality rates ranged from 7.73% to 71.23%. Interestingly, in the two urban areas, mosquitoes were found to be fully susceptible to chlorpyriphos-methyl 0.4%. Elevated activity of non-specific esterases and glutathione-S-transferases was reported, suggesting multiple resistance mechanisms involved in Ae. aegypti populations from Bobo-Dioulasso and Ouagadougou (including cytochrome P450). This update to the insecticide resistance status within Ae. aegypti populations in the two biggest cities is important to better plan dengue vectors control in the country and provides valuable information for improving vector control strategies in Burkina Faso, West Africa.

scholarly journals The nature of chemical innovation: new enzymes by evolution

2015 ◽  
Vol 48 (4) ◽  
pp. 404-410 ◽  
Author(s):  
Frances H. Arnold
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Reactive Intermediates ◽  
Transfer Reactions ◽  
Amino Acid Substitutions ◽  
Chemical Catalysis ◽  
Nitrene Transfer ◽  
Enzyme Systems ◽  
Natural Enzyme ◽  
And Function

AbstractI describe how we direct the evolution of non-natural enzyme activities, using chemical intuition and information on structure and mechanism to guide us to the most promising reaction/enzyme systems. With synthetic reagents to generate new reactive intermediates and just a few amino acid substitutions to tune the active site, a cytochrome P450 can catalyze a variety of carbene and nitrene transfer reactions. The cyclopropanation, N–H insertion, C–H amination, sulfimidation, and aziridination reactions now demonstrated are all well known in chemical catalysis but have no counterparts in nature. The new enzymes are fully genetically encoded, assemble and function inside of cells, and can be optimized for different substrates, activities, and selectivities. We are learning how to use nature's innovation mechanisms to marry some of the synthetic chemists’ favorite transformations with the exquisite selectivity and tunability of enzymes.

scholarly journals Polymorphisms of cytochrome P450 1A1, glutathione s-transferases M1 and T1 genes in ouangolodougou (Northern Ivory Coast)

2010 ◽  
Vol 33 (3) ◽  
pp. 434-437 ◽  
Author(s):  
Alfredo Santovito ◽  
Claudio Burgarello ◽  
Piero Cervella ◽  
Massimiliano Delpero
Keyword(s):  
Cytochrome P450 ◽  
Ivory Coast ◽  
Cytochrome P450 1A1 ◽  
Glutathione S Transferases

scholarly journals Reactive Intermediates in Cytochrome P450 Catalysis

2013 ◽  
Vol 288 (24) ◽  
pp. 17074-17081 ◽  
Author(s):  
Courtney M. Krest ◽  
Elizabeth L. Onderko ◽  
Timothy H. Yosca ◽  
Julio C. Calixto ◽  
Richard F. Karp ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Reactive Intermediates
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