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This cysteine scarcity disrupts PDI activity, particularly PDIA1, PDIA3, and PDIA4, which catalyze disulfide bond formation and isomerization, resulting in insulin misfolding, as evidenced by simulated Raman spectroscopy showing reduced S-S stretching (510540 cm 1 ) in sulfur-deficient states [45, 46]

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In addition, exacerbation of the reduction in ATP and observed phosphocreatine levels, is accompanied by an increase in ADP and orthophosphate levels, in both cardiac tissue and other organs (30)

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