The Cori cycle The lactic acid cycle is a metabolic pathway in which the lactate produced by glycolytic pathways in the muscle goes to the liver, where it is converted back to glucose. This compound returns again to the liver to be metabolized.
This metabolic pathway was discovered in 1940 by Carl Ferdinand Cori and his wife Gerty Cori, scientists from the Czech Republic. They both won the Nobel Prize in Physiology or Medicine.
The Cori cycle begins in the muscle fibers. In these tissues the obtaining of ATP occurs mainly by the conversion of glucose into lactate.
It is worth mentioning that the terms lactic acid and lactate, widely used in sports terminology, differ slightly in their chemical structure. Lactate is the metabolite produced by the muscles and is the ionized form, while lactic acid has an additional proton.
Muscle contraction occurs by hydrolysis of ATP.
This is regenerated by a process called "oxidative phosphorylation". This pathway occurs in slow (red) and fast (white) twitch muscle fiber mitochondria.
Fast muscle fibers are made up of fast myosins (40-90 ms), in contrast to lens fibers, made up of slow myosins (90-140 ms). The former produce more force but tire quickly.
Lactate reaches the liver through the blood. Again lactate is converted to pyruvate by action of the enzyme lactate dehydrogenase.
Finally, pyruvate is transformed to glucose by gluconeogenesis, using ATP from the liver, generated by oxidative phosphorylation..
This new glucose can return to the muscle, where it is stored in the form of glycogen and is used once again for muscle contraction..
Gluconeogenesis is the synthesis of glucose using components that are not carbohydrates. This process can take as raw material pyruvate, lactate, glycerol and most of the amino acids.
The process begins in the mitochondria, but most of the steps continue in the cell cytosol.
Gluconeogenesis involves ten of the reactions of glycolysis, but in reverse. It happens as follows:
-In the mitochondrial matrix, pyruvate is converted to oxaloacetate by the enzyme pyruvate carboxylase. This step requires a molecule of ATP, which becomes ADP, a molecule of COtwo and one of water. This reaction releases two H+ in the middle.
-Oxaloacetate is converted to l-malate by the enzyme malate dehydrogenase. This reaction requires a molecule of NADH and H.
-The l-malate exits the cytosol where the process continues. The malate changes back to oxaloacetate. This step is catalyzed by the enzyme malate dehydrogenase and involves the use of a molecule of NAD.+
-Oxaloacetate is converted to phosphoenolpyruvate by the enzyme phosphoenolpyruvate carboxykinase. This process involves a GTP molecule that passes into GDP and COtwo.
-Phosphoenolpyruvate becomes 2-phosphoglycerate by the action of enolase. This step requires a molecule of water.
-Phosphoglycerate mutase catalyzes the conversion of 2-phosphoglycerate to 3-phosphoglycerate.
-The 3-phosphoglycerate becomes 1,3-bisphosphoglycerate, catalyzed by the phosphoglycerate mutase. This step requires a molecule of ATP.
-1,3-bisphosphoglycerate is catalyzed to d-glyceraldehyde-3-phosphate by glyceraldehyde-3-phosphate dehydrogenase. This step involves a molecule of NADH.
-D-glyceraldehyde-3-phosphate becomes fructose 1,6-bisphosphate by aldolase.
-Fructose 1,6-bisphosphate is converted to fructose 6-phosphate by fructose 1,6-bisphosphatase. This reaction involves a water molecule.
-Fructose 6-phosphate is converted to glucose 6-phosphate by the enzyme glucose-6-phosphate isomerase.
-Finally, the enzyme glucose 6-phosphatase catalyzes the passage of the latter compound to α-d-glucose.
Muscle fibers are unable to carry out the gluconeogenesis process. In such a case that it could, it would be a totally unjustified cycle, since gluconeogenesis uses much more ATP than glycolysis.
Furthermore, the liver is an appropriate tissue for the process. In this organ it always has the necessary energy to carry out the cycle because there is no lack of Otwo.
Traditionally it was thought that during cell recovery after exercise, about 85% of the lactate was removed and sent to the liver. Then the conversion to glucose or glycogen occurs.
However, new studies using rats as model organisms reveal that the frequent fate of lactate is oxidation..
Furthermore, different authors suggest that the role of the Cori cycle is not as significant as previously believed. According to these investigations, the role of the cycle is only reduced to 10 or 20%.
When exercising, the blood achieves a maximum accumulation of lactic acid, after five minutes of training. This time is enough for the lactic acid to migrate from the muscle tissues to the blood..
After the muscle training stage, blood lactate levels return to normal values after one hour.
Contrary to popular belief, the accumulation of lactate (or lactate itself) is not the cause of muscle exhaustion. It has been shown that in workouts where lactate accumulation is low, muscle fatigue occurs.
The true cause is thought to be a decrease in pH within the muscles. The pH may drop from the baseline value of 7.0 to 6.4, which is considered quite low. In fact, if the pH is kept close to 7.0, even though the lactate concentration is high, the muscle does not fatigue..
However, the process that leads to fatigue as a consequence of acidification is not yet clear. It may be related to the precipitation of calcium ions or a decrease in the concentration of potassium ions.
Athletes massage and ice their muscles to promote the passage of lactate into the blood.
There is a metabolic pathway almost identical to the Cori cycle, called the alanine cycle. Here the amino acid is the precursor of gluconeogenesis. In other words, alanine takes the place of glucose..