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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

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However, considering that kinases of MAPK pathways are inactivated even in the presence of extracellular stimuli, it can be assumed that phosphatases mediate elaborate regulation in terms of both magnitude and duration of signals [39,40]