Aminoacylase 1-catalysed deacetylation of bioactives epoxides mycotoxin-derived mercapturates; 3,4-epoxyprecocenes as models of cytotoxic epoxides

Biochimie
P StockerJosette Perrier

Abstract

The mycotoxin aflatoxin B1 (AFB1) is a carcinogenic food contaminant which is metabolically activated by epoxydation. The metabolism of mycotoxins via the mercapturate metabolic pathway was shown, in general, to lead to their detoxication. Mercapturic acids thus formed (S-substitued-N-acetyl-l-cysteines) may be accumulated in the kidney and either excreted in the urine or desacetylated by Acylase 1 (ACY1) to yield cysteine S-conjugates. To be toxic, the N-acetyl-l-cysteine-S-conjugates first have to undergo deacetylation by ACY 1. The specificity and rate of mercapturic acid deacetylation may determine the toxicity, however the exact deacetylation processes involved are not well known. The aim of this study was to investigate the role of ACY1 in the toxicity of some bioactive epoxides from Aflatoxin B1. We characterized the kinetic parameters of porcine kidney and human recombinant aminoacylase-1 towards some aromatic and aliphatic-derived mercapturates analogue of mycotoxin-mercapturic acids and 3,4-epoxyprecocene, a bioactive epoxide derivated from aflatoxin. The deacetylation of mercapturated substrates was followed both by reverse phase HPLC and by TNBS method. Catalytic activity was discussed in a structure-function relati...Continue Reading

References

Dec 26, 2001·Nucleic Acids Research·Neil D RawlingsAlan J Barrett
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May 5, 2007·Cell Biology International·Natacha CignaJosette Perrier
Mar 18, 2008·Biochemistry·Holger A LindnerTraian Sulea

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Citations

Mar 7, 2013·Dalton Transactions : an International Journal of Inorganic Chemistry·Vivian C SilveiraAna M da Costa Ferreira
Jan 17, 2020·Critical Reviews in Toxicology·Patrick E Hanna, M W Anders
Aug 14, 2020·ACS Chemical Biology·Simon VobrubaJiri Janata
Jun 26, 2021·Pharmacology & Therapeutics·Brandán PedreTobias P Dick

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