Cori cycle (WP1946)

The Cori cycle (also known as the Lactic acid cycle), named after its discoverers, Carl Ferdinand 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 metabolized back to lactate. Muscular activity requires ATP, which is provided by the breakdown of glycogen in the skeletal muscles. The breakdown of glycogen, a process known as glycogenolysis, releases glucose in the form of glucose-1-phosphate (G-1-P). The G-1-P is converted to G-6-P by the enzyme phosphoglucomutase. G-6-P is readily fed into glycolysis, (or can go into the pentose phosphate pathway if G-6-P concentration is high) a process that provides ATP to the muscle cells as an energy source. During muscular activity, the store of ATP needs to be constantly replenished. When the supply of oxygen is sufficient, this energy comes from feeding pyruvate, one product of glycolysis, into the Krebs cycle. When oxygen supply is insufficient, typically during intense muscular activity, energy must be released through anaerobic metabolism. Lactic acid fermentation converts pyruvate to lactate by lactate dehydrogenase. Most importantly, 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. Instead of accumulating inside the muscle cells, lactate produced by anaerobic fermentation is taken up by the liver. This initiates the other half of the Cori cycle. In the liver, gluconeogenesis occurs. From an intuitive perspective, gluconeogenesis reverses both glycolysis and fermentation by converting lactate first into pyruvate, and finally back to glucose. The glucose is then supplied to the muscles through the bloodstream; it 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. Overall, 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. As a result, the cycle cannot be sustained indefinitely. The intensive consumption of ATP molecules indicates that the Cori cycle shifts the metabolic burden from the muscles to the liver. Source: [https://en.wikipedia.org/wiki/Cori_cycle Wikipedia] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP1946 CPTAC Assay Portal]

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