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However, the long-term presence of IS can cause metabolic imbalances, overactivation of the pentose phosphate pathway, leading to the conversion of glucose shunt to 5-phosphoribose, which in turn reduces the production of key metabolites in the tricarboxylic acid cycle, such as α-ketoglutaric acid and malic acid, leading to mitochondrial dysfunction, manifested by decreased oxygen consumption rates and reduced ATP levels (71)

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