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These authors contributed equally: Nisansala Chandimali, Seon Gyeong Bak

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However, excessive activation reduces the proportion of glucose entering glycolysis and the TCA cycle, impairing energy production efficiency ( As the core of energy metabolism, the TCA cycle exhibits abnormalities primarily stemming from insufficient substrate supply and inhibited activity of key enzymes—ultimately leading to reduced energy production efficiency and dysregulation of metabolic intermediates ( These TCA cycle abnormalities are further characterized by the accumulation of intermediates: in the lung tissue of COPD patients and smoke-exposed mice, TCA intermediates such as citrate, alpha-ketoglutarate, and succinate accumulate—with elevated alpha-ketoglutarate also detected in urine