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L. F. Chasseaud

Bio: L. F. Chasseaud is an academic researcher. The author has contributed to research in topics: Glutathione reductase & Enzyme. The author has an hindex of 1, co-authored 1 publications receiving 302 citations.

Papers
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Journal ArticleDOI
TL;DR: Rat-liver supernatant catalyses the reaction of a number of other alphabeta-unsaturated compounds, including aldehydes, ketones, lactones, nitriles and nitro compounds, with glutathione: separate enzymes may be responsible for these reactions.
Abstract: 1. Rat-liver supernatant catalyses the reaction of diethyl maleate with glutathione. 2. Evidence is presented that the enzyme involved is different from the known glutathione-conjugating enzymes, glutathione S-alkyltransferase, S-aryltransferase and S-epoxidetransferase. 3. Rat-liver supernatant catalyses the reaction of a number of other alphabeta-unsaturated compounds, including aldehydes, ketones, lactones, nitriles and nitro compounds, with glutathione: separate enzymes may be responsible for these reactions.

304 citations


Cited by
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Book ChapterDOI
TL;DR: The knowledge of the way in which mutagens and carcinogens are metabolized is essential to a better understanding of their mode of action and of the processes for their detoxication.
Abstract: Publisher Summary This chapter discusses the role of glutathione (GSH) and glutathione s-transferases in metabolism of chemical carcinogens and other electrophilic agents. GSH is a tripeptide (I) that is present in nearly all living cells and is the most abundant sulfhydryl compound present in animal tissues, mainly in the cytosol. The chapter illustrates the wide range of electrophilic agents, including several known mutagens and carcinogens, which conjugate with GSH, a process usually catalyzed by the GSH S-transferases. This conjugation is probably a protective mechanism and is the initial stage in mercapturic acid biosynthesis for the elimination of foreign compounds from the body. GSH S-transferases provide protection not only by catalyzing the conjugation of a potential toxicant with GSH, but also by preferentially binding, even covalently, that toxicant. The reactive electrophiles that conjugate with GSH also bind to DNA, RNA, and protein and identification of GSH conjugates provide information on the nature of these biologically active intermediates or even their immediate precursors. Thus, the knowledge of the way in which mutagens and carcinogens are metabolized is essential to a better understanding of their mode of action and of the processes for their detoxication.

1,124 citations

Book ChapterDOI
TL;DR: There appears to be sufficient enzyme for all three roles in detoxification of glutathione S-transferases; the binding of bilirubin is an example of a major function common to all higher species.
Abstract: The physiological roles of the glutathione S-transferases, by whatever name, seem to result in detoxification As is true of albumin, members of this group of proteins bind an enormous number of compounds that appear to have in common only hydrophobic topography; the binding of bilirubin is an example of a major function common to all higher species If the ligand bears a sufficiently electrophilic center, it will be attacked by the nucleophile GSH; such compounds would be the substrates of the enzyme And should such a ligand be extraordinarily reactive--as, for example, some of the epoxide carcinogens generated by the cytochrome P450-linked, mixed-function oxidases, or even 1-chloro-2,4-dinitrobenzene--then reaction may occur either with GSH or irreversibly with the transferase itself By reason of the wide distribution and high intracellular concentration of these proteins, there appears to be sufficient enzyme for all three roles in detoxification

651 citations

Journal ArticleDOI
TL;DR: Results indicate that this increase in YAP1‐specific binding to DNA is not due to an increase in synthesis of Yap1 protein, but rather results from modification of pre‐existing protein.
Abstract: The role of the YAP1 transcription factor in the response of Saccharomyces cerevisiae cells to a variety of conditions that induce oxidative stress has been investigated. Cells deficient in YAP1 were found to be hypersensitive to hydroperoxides and thioloxidants, whereas overexpression of YAP1 conferred hyper-resistance to the same conditions. These treatments resulted in an increase in YAP1-specific binding to DNA together with an increase in YAP1 dependent transcription. Our results indicate that this increase is not due to an increase in synthesis of YAP1 protein, but rather results from modification of pre-existing protein. Using a specific genetic screen, the TRX2 gene, one of two genes of S. cerevisiae that encode thioredoxin protein, was identified as being essential for YAP1 dependent resistance to hydroperoxides. Furthermore, efficient expression of TRX2 was dependent on YAP1 and enhanced under conditions of oxidative stress.

475 citations

Journal ArticleDOI
TL;DR: The data presented show that measuring peptide reactivity has utility for screening chemicals for their skin sensitization potency and thus potential for reducing the authors' reliance on animal test methods.

450 citations