Different cells in the human body need to release energy during high periods of energy demand, like during intense exercise. The Cori cycle is a metabolic pathway involving the interconversion of glucose and lactate between the muscles and the liver.
The Cori cycle is called lactic acid shuttle or lactic acid cycle. Cori Cycle is named after the husband and wife scientists duo Gertrude (Gerty) and Carl Cori, who introduced and descirbed this cycle from 1925 to 1950 AD. However, they jointly recieved the novel prize in physiology and medicine in 1947 for the discovery of this cycle.
The cycle completes in a five-step process where four ATP molecules are used. The five steps involve; Lactate production, Transport of lactate to the liver, Conversion of lactate to glucose, The release of glucose in the bloodstream, and Uptake of glucose by other cells.
Table of Contents
Steps of Cori Cycle
This metabolic pathway requires three different types of human cells; liver, blood, and muscle or other high energy-requiring cells. This cycle is vital for maintaining glucose levels during high energy demand periods like intense exercise.
As discussed earlier, the Cori cycle occurs in five steps; lactic acid production, transportation of lactate to the liver, glucose production, the release of glucose in the blood, and glucose uptake by required cells.
- Lactate production: Glycogen stored in the muscle cells converts to glucose via glycogenolysis. During high energy demand, especially in muscle cells, the pyruvate produced after glycolysis of glucose follows the anaerobic pathway to produce lactic acid or lactate. The anaerobic fate of pyruvate occurs due to a lack of oxygen in these cells. So, this cycle is also termed anaerobic glycolysis for lactic acid production. Here, the conversion of glucose to pyruvate produces two ATP molecules.
- Transport of lactate to the liver: The lactate produced cannot be utilized by muscle cells. Liver cells can only use lactate. So it is transported to liver cells via the bloodstream.
- Gluconeogenesis: Gluconeogenesis is a metabolic pathway that helps produce glucose from non-carbohydrate compounds in the liver cells. During the lactate cycle, lactic acid converts into glucose. It is a complex procedure requiring multiple enzymes. It requires six ATP molecules.
- Release of glucose in the blood: The newly formed glucose is released into the bloodstream. This release helps maintain the blood glucose level during high-intensity exercise periods. Glucose is a fuel source for tissues, including the brain, RBCs, and muscles.
- Glucose uptake by muscles and other tissues: The glucose in the bloodstream is uptaken by cells like muscles, the brain, and other tissues. Here the glucose converts into pyruvate by glycolysis, which follows the aerobic fate to produce carbon dioxide. The CO2 is then released outside the body via the lungs.
The energy calculation during the Cori cycle is as follows:
Glucose/Glycogen → Pyruvate; produces 2 ATP molecules
Lactate → Glucose; requires 6 ATP molecules
So, a total of 4 ATP molecules is used in this cycle.
Although it uses four molecules of ATP, it is an essential cycle for energy production. This high amount of energy production is because, after the glucose uptake by different cells, the glucose enters the TCA cycle, producing almost 10 ATPs per acetyl CoA molecule.
Regulation of Cori Cycle
As discussed earlier, lactic acid cycle is an essential process in the body that helps control blood glucose levels and provides energy during an intense situation. So, this cycle must be tightly regulated by internal as well as external factors. Numerous factors regulate the Cori cycle. External factors include exercise intensity and nutrition intake, and internal factors include hormonal control, oxygen, and glucose availability.
- Hormonal regulation: The hormones insulin, glucagon, and adrenalin help regulate the Cori cycle. Adrenalin is a stress hormone that promotes the release of glucose in the bloodstream from liver cells. Glucagon prevents the blood glucose level from dropping lower than average blood sugar level, so in the case of the Cori cycle, glucagon also promotes the release of glucose in the blood. Insulin helps uptake glucose from the blood into the targeted cell.
- Regulation due to exercise intensity: The higher the power, the more energy is required. So, the higher the exercise intensity, the higher the number of Cori cycles.
- Nutritional intake: High carbohydrate diet enhances/promotes the steps of the Cori cycle. Likewise, the higher the amount of lipid and protein in the diet, the less chance of Cori cycle occurrence.
- Availability of oxygen: If oxygen is unavailable in muscle cells, it triggers the formation of lactate in the cell. Lactate act as the substrate for the Cori cycle. Once oxygen is available, the Cori cycle is halted.
- Glucose availability: Once the glucose level in the blood drops, the Cori cycle activates, which helps increase the blood glucose level. Whereas, once the blood glucose level increases and uptake by the required cells is complete, the Cori cycle stops.
Importance of Lactic Acid Cycle
The lactic acid cycle is a crucial mechanism that helps adapt the body to various energy demands. It ensures a steady supply of glucose in cells even during a temporary shortage of oxygen. It is the most essential role of the lactic acid cycle. Let us discuss the importance of the Cori cycle in the human body:
- Prevent acidosis in muscles: Acidosis is the accumulation of acid in cells. In the case of muscle cells, lactate or lactic acid accumulates in the absence of oxygen, causing cramps, nausea, and weakness. It usually can happen during exercise, and activation of the Cori cycle helps prevent acidosis.
- Increase exercise intensity: Exercise demands a high amount of energy without oxygen. The Cori cycle can help increase glucose levels in the blood by utilizing the lactate from muscles. The glucose helps increase power which helps in increasing the intensity of exercise.
- Maintain glucose level and energy during stressful times: Cori cycle helps maintain the level of glucose and vitality during stressful times, not only exercise but also mental stress. So, it is also an essential process during flight or fight response.
Disorders Related to Cori Cycle
The disruption and absence of the Cori cycle in humans can cause many complications, like Cori’s disease, lactic acidosis, McCardle’s disease, and hypoglycemia during exercise.
- Cori’s disease: Glycogen storage disease IIi (GSD-IIi) or Cori/Forbes disease is a genetic condition that stops the breakdown of glycogen to glucose. The breakdown is halted due to the absence of enzymes required for glycogenolysis. This condition causes muscle weakness, hypertrophy of the liver (enlargement of the liver), and delayed growth in children.
- Exercise-induced hypoglycemia: Lack of the Cori cycle can cause lead to exercise-induced hypoglycemia (EIH). EIH can cause dizziness and weakness while doing exercise. Here the blood glucose level decreases significantly.
- McArdle’s disease: It is also a genetic disorder where an individual lacks the enzyme to break down glucose. People with this disease can experience fatigue, muscle cramps, and weakness during physical exercise.
- Lactic Acidosis: Lactic acidosis is a disorder where accumulation of lactic acid occurs in the skeletal muscle cells. It can lead to extreme fatigue, body weakness, abdominal discomfort, and headache.
- Matthews, C. K., van Holde, K.E., and Ahern, K. G., Biochemistry, 3rd Ed., Addison Wesley Longman, 2000
- National Center for Biotechnology Information (2023). PubChem Pathway Summary for Pathway WP1946, Cori cycle, Source: WikiPathways. Retrieved August 9, 2023 from https://pubchem.ncbi.nlm.nih.gov/pathway/WikiPathways:WP1946.
- Nelson, D. L., Cox, M. M., & Lehninger, A. L. (2005). Hormonal Regulation and Integration of Mammalian Metabolism. In Principles of biochemistry (3rd ed., pp. 898–899). essay, Freeman.