Cori cycle: Introduction, Steps, Regulation, and disorders

Define Cori cycle.

The Cori cycle (or lactic acid cycle) is a metabolic mechanism that occurs in the liver and muscles. It refers to the means through which lactic acid created by anaerobic glycolysis within muscle cells is carried to the liver & transformed into glucose. It can then be utilized as a form of energy by the muscles again.

In a deficiency of oxygen, muscle cells depend on anaerobic metabolism to generate energy. As a consequence, this process produces lactic acid, which can accumulate in the muscles and induce tiredness. The Cori cycle, on the other hand, allows the body to regenerate this lactic acid. It is then utilized as an alternative source of energy, extending activity and decreasing tiredness.

Gluconeogenesis, a procedure carried out in the liver, transforms lactic acid into glucose, that is subsequently released into the circulation and delivered back to the muscles. The Cori cycle is crucial for preserving blood glucose levels and giving muscles fuel during times of intense activity.

Steps of Cori cycle

The body use the Cori cycle, a vital metabolic process that happens in the liver and muscles, to recycle lactic acid and keep blood glucose levels stable while engaging in intense physical activity.  The Cori cycle’s stages and its mechanism for supplying energy to the muscles will be covered in this article.

Step 1:

Anaerobic Glycolysis

The Cori cycle commences with anaerobic glycolysis, which happens in muscle cells while oxygen isn’t present. Glucose is broken down to pyruvate, which is subsequently transformed onto lactic acid throughout this process of breakdown.  This process produces energy in the form of ATP, that cells in the muscle utilize to contract.

Step 2:

Lactic Acid Transport

Lactic acid is created in cells of muscles and then delivered to the liver via the circulation. The liver cells are capable of transforming lactic acid to glucose. The muscle cells can utilize these glucose as an energy source.

Step 3:


Lactic acid is transformed into glucose in the liver via a process known as gluconeogenesis. This includes the production of glucose from non-carbohydrate sources like lipids and amino acids. The complex method of glucose synthesis needs the activation of multiple enzymes, such as lactate dehydrogenase and glucose-6-phosphatase.

Step 4:

Glucose Transport

After being created in the liver, glucose is reintroduced into the circulation and supplied to the muscle cells. To power muscular contraction and continue exercising, this glucose may be utilized as a source of energy.

Step 5:

Aerobic Respiration

Glucose gets broken down within muscle cells via aerobic respiration, which provides energy in the form of ATP. This process demands the use of oxygen and results in the production of carbon dioxide as a byproduct, which is subsequently carried back to the lungs for elimination.

Diagram of Cori cycle
Diagram of Cori cycle

Regulation of Cori cycle

The Cori cycle is a system of metabolic processes that is controlled by a number of elements that make sure that the human body always has an adequate amount of glucose for energy. The following are some of the important regulatory factors:

  1. Exercise intensity: The rate of lactic acid generation and the need for glucose can be affected by the level of exercise.  As exercise intensity rises, it also raises lactic acid generation and the requirement for glucose, which can drive the Cori cycle to keep blood glucose levels stable.
  2. Hormonal control: Hormones like insulin, glucagon, and adrenaline can influence the Cori cycle by influencing glucose absorption and releasing in the liver and muscles. Insulin promotes glucose absorption by muscle cells, whereas glucagon and adrenaline induce the release of glucose from the liver.
  3. Oxygen availability: The Cori cycle is triggered by a shortage of oxygen in muscle cells, which causes anaerobic metabolism and the formation of lactic acid. When there is enough oxygen, aerobic metabolism takes over, producing more ATP and reducing the requirement for the Cori cycle.
  4. Nutritional status: The supply of nutrients such as carbs and lipids in the Cori cycle can also impact the pace of glucose synthesis and utilization. A low-carbohydrate or high-fat diet can disrupt the Cori cycle, whereas a high-carbohydrate diet can enhance it.

Cori cycle disorders

There are various disorders associated to the Cori cycle, including:

  1. Cori disease: Cori disease, also known as glycogen storage disease type III, is a rare hereditary condition that inhibits the body’s capacity of breaking down glycogen to glucose. This causes glycogen buildup in the liver and muscles, resulting in symptoms such as muscular weakness, swollen liver, and low levels of blood sugar. 
  2. McArdle disease: McArdle disease, also known as glycogen storage disease type V, is a rare hereditary ailment that affects the degradation of glycogen.  It is brought about by a lack of an enzyme called myophosphorylase. This affects the Cori metabolic cycle’s capacity to transform glycogen into glucose for energy. Symptoms include muscular discomfort, cramping, and weariness during activity.
  3. Lactic acidosis: Lactic acidosis is a disorder that involves lactic acid accumulation in the body. It can be a result of a number of causes, including reduced oxygen transport, mitochondrial malfunction, or Cori cycle abnormalities. Fatigue, muscular weakness, nausea, and fast breathing are some of the symptoms.
  4. Exercise-induced hypoglycemia: This is a condition whereby blood sugar levels drop excessively after activity. It is believed to be a result of a combination of higher muscle glucose absorption and reduced liver glucose synthesis.

Cori cycle disorders are often treated by controlling symptoms and avoiding triggers that aggravate symptoms. Enzyme replacement treatment or liver transplantation may be indicated in some circumstances. Individuals with a family history of these conditions may benefit from genetic counseling as well.

Energy calculation of Cori cycle

The Cori cycle involves the conversion of glucose to lactate in the muscles, followed by the conversion of lactate back to glucose in the liver through gluconeogenesis. This process consumes ATP, which is required for the various enzymatic reactions involved in the cycle.

Cori cycle

The net energy cost of the cycle can be calculated by considering the ATP required for each step of the process. The breakdown of one molecule of glucose to two molecules of lactate in the muscle consumes two ATP molecules through glycolysis. The conversion of two lactate molecules back to one glucose molecule in the liver through gluconeogenesis requires six ATP molecules. Therefore, the net energy cost of the Cori cycle is four ATP molecules per glucose molecule converted.

However, it’s important to note that the it also plays a critical role in energy production and glucose homeostasis in the body. It can ultimately lead to a net gain in energy for the organism. Additionally, the recycling of lactate through the Cori cycle can help to maintain muscle function and prevent fatigue during prolonged exercise.

Binod G C

I'm Binod G C (MSc), a PhD candidate in cell and molecular biology who works as a biology educator and enjoys scientific blogging. My proclivity for blogging is intended to make notes and study materials more accessible to students.

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