Cori cycle (WP1946)

The Cori cycle is also known as the Lactic acid cycle, and refers to the metabolic process in which lactate produced by anaerobic glycolysis in the muscles is transported to the liver where it is converted to glucose, which then returns to the muscles and is metabolized back to lactate. It was discovered by Carl Ferdinand Cori and Gerty Cori. Muscular activity requires ATP, which is provided by the breakdown of glycogen in the skeletal muscles. During glycogenolysis, the breakdown of glycogen produces glucose in the form of glucose-1-phosphate (G-1-P), which is then converted to G-6-P by phosphoglucomutase. G-6-P is fed into glycolysis, a process that provides ATP to the muscle cells as an energy source. It can also go into the pentose phosphate pathway if G-6-P concentration is high. During muscular activity, ATP stores need to be constantly replenished. When the oxygen supply is sufficient, this energy comes from feeding pyruvate (from glycolysis), to the Krebs cycle. When the oxygen supply is insufficient, for example during intense muscular activity, energy must be released through anaerobic metabolism. During lactic acid fermentation, lactate dehydrogenase converts pyruvate to lactate. Fermentation regenerates NAD+, maintaining the NAD+ concentration so that additional glycolysis reactions can occur. The fermentation step oxidizes the NADH produced by glycolysis back to NAD+, transferring two electrons from NADH to reduce pyruvate into lactate. Lactacte produced by anaerobic fermentation does not accumulate inside the muscle cells, instead it is taken up by the liver, which initiates the other half of the Cori cycle. In the liver, gluconeogenesis reverses both glycolysis and fermentation by converting lactate first into pyruvate, and finally back to glucose. The glucose is supplied to the muscles through the bloodstream and is ready to be fed into further glycolysis reactions. If muscle activity has stopped, the glucose is used to replenish the supplies of glycogen through glycogenesis. The glycolysis part of the cycle produces 2 ATP molecules at a cost of 6 ATP molecules consumed in the gluconeogenesis part. Each iteration of the cycle must be maintained by a net consumption of 4 ATP molecules. Therefor, the cycle cannot be sustained indefinitely. The Cori cycle shifts the metabolic burden from the muscles to the liver. Source: Adapted from Wikipedia. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.

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