How does the Cori cycle work?

The Cori cycle, also called lactic acid cycle, describes a metabolic pathway in which lactic acid produced in muscle cells by anaerobic glycolysis reaches the liver and is converted back into glucose. This cycle was explained for the first time in 1929 by the marriage of biochemists Carl Ferdinand Cori and Gerty Theresa Coriwinners of the Nobel Prize in medicine in 1947 together with Bernardo Houssay (not for the Cori cycle but for the discovery of the catabolic conversion of glycogen).

Functioning

Muscular activity consumes ATP (adenosine triphosphate), the molecule from which muscle cells obtain the energy they need. ATP is obtained by glucose metabolism and this glucose is obtained in turn either from the blood circulation or by degradation of muscle glycogen stores (glycogenolysis). In long-term physical activities, such as a marathon, lipolysis (metabolization of fat) is also involved.

The metabolism of glucose begins with its transformation into pyruvate in a reaction known as glycolysis. For each molecule of glucose, glycolysis consumes two molecules of ATP and two molecules of NAD.+ Y produces two pyruvate molecules, four ATP molecules (minus the two consumed, net yield of 2 ATP) and two NADH molecules. If there is enough oxygen, the pyruvate passes to the mitochondrial matrix to continue being oxidized in the Krebs cycle, where it generates 32 more ATP (16 for each pyruvate), and the NADH enters the respiratory chain where it generates 5 more ATP molecules.

In certain situations, for example when intense activity is carried out, the muscle cells do not receive oxygen quickly enough to replenish the oxygen consumed in the respiratory chain. NADH is not "burned" and is used for reduce pyruvate and transform it into lactic acid (it is dissolved in the form of lactate). This reaction is known as lactic fermentation (the type of anaerobic glucose metabolism carried out by humans) and does not generate more ATP but NADH is converted back to NAD+ making it possible for glycolysis of another glucose molecule to begin again.

That is, when there is not enough oxygen in the muscle, glycolysis generates 2 ATP, two molecules of lactic acids and the consumed NADH is regenerated. The lactate passes into the blood circulation and through it reaches the liver, beginning the second stage of the Cori cycle..

in the liver, lactate is converted back to glucose (gluconeogenesis). This glucose passes into the bloodstream and can be reused by muscle cells as an energy source. If the intensity of muscular activity remains intense, glucose will again generate lactic acid and a new round of the Cori cycle begins. If activity has decreased, glucose can follow normal aerobic respiration, much more efficient than lactic acid fermentation, or be used to synthesize glycogen and replenish muscle stores that had been previously used. Cori's cycle is closed.

Hepatic gluconeogenesis from lactate requires 6 ATP. This makes Cori's cycle has a net expenditure of 4 ATP. and implies that the metabolic load during intense physical activity shifts from the muscles to the liver. The high energy demand of intense muscular activity produces lactic acid rapidly. When the liver's ability to metabolize lactic acid is exceeded, blood pH begins to drop, potentially reaching dangerous levels and producing a known disorder lactic acidosis It manifests itself with various symptoms, such as weakness, cramps and nausea.

That is, due to the consumption of ATP and the limited capacity of hepatic gluconeogenesis, the Cori cycle cannot be maintained indefinitely. Muscle cells, and of course the rest of the body, require restitution of oxygen supply or they will continue to ferment glucose and enter the Cori cycle uninterruptedly producing lactic acidosis (this is what happens in the event of death and lactic acidosis becomes such that it is the underlying cause of rigor mortis).

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