During tissue ischemia succinate accumulates. Herein, literature spanning the past nine decades is reviewed leaning towards the far greater role of Krebs cycle's canonical activity yielding succinate through α-ketoglutarate -> succinyl-CoA -> succinate even in hypoxia, as opposed to reversal of succinate dehydrogenase. Furthermore, the concepts of i) a diode-like property of succinate dehydrogenase rendering it difficult to reverse, and ii) the absence of mammalian mitochondrial quinones exhibiting redox potentials in the [-60, -80] mV range needed for fumarate reduction, are discussed. Finally, it is emphasized that a "fumarate reductase" enzyme entity reducing fumarate to succinate found in some bacteria and lower eukaryotes remains to be discovered in mammalian mitochondria.
Keywords: Anoxia; Fumarate; Hypoxia; Substrate-level phosphorylation; Succinate dehydrogenase; TCA cycle.
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