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All species generate NADPH intracellularly, which fuels disulfide reductase systems Mammals have an NADPH-independent disulfide reductase system fueled by methionine Transsulfuation reversal allows Met-fueled reductase system yet makes Met essential Transsulfuration reversal and a Se- dependent TrxR family co-evolved with metazoans Metazoan selenoprotein TrxR1 and transsulfuration each support redox signaling Acknowledgments Funding to the authors came from the US National Institutes of Health (AG055022 and CA215784)

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