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The acetyl group reduces the reactivity of the thiol (SH), making NAC less toxic and less susceptible to oxidation than Cys [7]Rehman SU, Vacek T, Ali A et al

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I havent seen any good studies to show that it negates the effects of methotrexate

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This site is formed by a combination of alpha helices and beta sheets, creating a pocket that specifically accommodates the tripeptide glutathione