Which Way Does the Citric Acid Cycle Turn During Hypoxia? The Critical Role of α-Ketoglutarate Dehydrogenase Complex

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 a-ketoglutarate dehydrogenase complex dictating their directionalities. (C) 2013 Wiley Periodicals, Inc.