The Cori cycle, named after its discoverers, Carl Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is converted to glycogen.[1]
Muscular activity leads to the release of epinephrine (adrenaline) which causes the breakdown of glycogen in the muscles. The breakdown of glycogen generates ATP which is used by muscular activity as an energy source. Since throughout muscular activity ATP is used to supply energy, it needs to be constantly replenished. In the beginning of muscular activity, glycolysis produces pyruvic acid that is converted to acetyl CoA which is metabolized in the citric acid cycle to make ATP through the use of the electron transport chain. However, as muscle activity continues, there is no longer enough oxygen for use at the end of the electron transport chain. When the oxygen in the cells runs out, the citric acid cycle is suppressed and pyruvic acid begins to accumulate. Yet, glycolysis can carry on even under anaerobic conditions in contrast to the citric acid cycle which works under only aerobic conditions. In the Cori cycle, glycolysis continues when pyruvic acid is converted back to lactic acid. Pyruvic acid is reduced to lactic acid by lactate dehydrogenase, which removes the protons from the NADH that were created during glycolysis and transfers them to pyruvic acid, creating lactic acid. This occurs in order to maintain a concentration of NAD+ that can be reduced during glycolysis, so that glycolysis can continue. The lactic acid is then taken up by the liver in the next part of the cycle. The liver converts the lactic acid back to pyruvic acid and then to glucose through gluconeogenesis. The glucose then enters the blood and returns to the muscles to be used for energy if muscle activity has continued. If muscle activity has stopped by this time then the glucose is used to replenish the supplies of glycogen through glycogenesis.[2]. Note that in the Cori cycle the gluconeogenic leg of the cycle is energy consuming. While there is a gain of 2 moles of ATP in the anaerobic glycolysis of glucose, there is a cost of 6 moles of ATP in the gluconeogenesis part of the cycle. The cost of the 4 moles of ATP means the cycle cannot be sustained continuously.[3]
Significance
The cycle's importance is based on the prevention of lactic acidosis in the muscle under anaerobic conditions. The accumulation of lactic acid causes muscle pain and cramps; however, normally before this happens the lactic acid is moved out of the muscles into the liver.[4].
The cycle is also important in producing ATP, an energy source, during muscle activity. The Cori cycle functions more efficiently when muscle activity has ceased because the oxygen debt can be made up so that the citric acid cycle and electron transport chain also work.[5].
Smith, A.D., Datta, S.P., Smith, G. Howard, Campbell, P.N., Bentley, R., (Eds.) et al.(1997) Oxford Dictionary of Biochemistry and Molecular Biology. New York: Oxford University Press.
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