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

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Abstract

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.

Original languageEnglish
Pages (from-to)1030-1043
Number of pages14
JournalJournal of Neuroscience Research
Volume91
Issue number8
DOIs
Publication statusPublished - Aug 2013

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Ketoglutarate Dehydrogenase Complex
Citric Acid Cycle
Oxidative Phosphorylation
Electron Transport
Metabolic Networks and Pathways
Phosphates
Phosphorylation
Hypoxia

Keywords

  • Cancer
  • Energy metabolism
  • Krebs cycle
  • Mitochondria
  • Tricarboxylic acid cycle

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

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