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One possible source for an enzyme to catalyze the next step in a pathway evolving in the forward direction is the enzyme that catalyzed the last step, as this enzyme has a binding site that accommodates the product of the last reaction, and that product is the substrate for the next reaction

These data were approved by Raheem et al

G6PD deficiency which reduces NADPH production phenocopies GSR impairment for exactly this reason: less NADPH means less GSR-driven GSSG reduction, less available GSH, and more oxidative stress under equivalent ROS production

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