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Under the limiting oxygen conditions experienced in by vigorous exercise, the configuration of NADH by glycolysis exceeds the ability of the respiratory chain to oxidize it back to NAD+. The pyruvate produced by glycolysis in muscle is then converted to lactate by lactate dehydrogenase, a reaction which regenerates NAD+ and so allows glycolysis to continue to produce ATP. Furthermore, lactate is a metabolic dead-end in which it cannot be metabolized further until it is converted back to pyruvate. The Lactate diffuses out of the muscle and is carried in the bloodstream to the liver. Here it spread into liver cells and is converted back to pyruvate by lactate dehydrogenase. The pyruvate is then transformed to glucose by gluconeogenesis and the glucose is released back into the bloodstream ready to be taken up by skeletal muscle and brain. This cycle of reactions shown in the figure is known as the Cori cycle.
The enzyme in the TCA cycle that catalyzes a substrate level phosphorylation is -citrate dehydrogenase -succinate thiokinase -isocitrate dehydrogenase
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