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J Neurosci Res. 2013 Aug;91(8):1030-43. doi: 10.1002/jnr.23196. Epub 2013 Feb 1.

Which way does the citric acid cycle turn during hypoxia? The critical role of α-ketoglutarate dehydrogenase complex.

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Department of Medical Biochemistry, Semmelweis University, Budapest 1094, Hungary.


The citric acid cycle forms a major metabolic hub and as such it is involved in many disease states involving energetic imbalance. In spite of the fact that it is being branded as a "cycle", during hypoxia, when the electron transport chain does not oxidize reducing equivalents, segments of this metabolic pathway remain operational but exhibit opposing directionalities. This serves the purpose of harnessing high-energy phosphates through matrix substrate-level phosphorylation in the absence of oxidative phosphorylation. In this Mini-Review, these segments are appraised, pointing to the critical importance of the α-ketoglutarate dehydrogenase complex dictating their directionalities.

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