The Cori cycle allows muscles to function without oxygen by converting lactate, a waste product of glycolysis, back into glucose through enzymatic reactions in the liver. This process is critical for maintaining blood sugar levels and meeting the high energy demands of muscle cells during exercise. However, lactic acidosis can occur when energy demand exceeds the liver’s ability to convert lactate to glucose, causing symptoms such as hyperventilation and abdominal cramps.
The Cori cycle describes the linked metabolic pathways by which muscles, even in the absence of oxygen, remain able to function. This occurs as a result of the liver’s ability to convert a muscle’s chemical waste product back into its source of energy. The cycle was first mapped in 1929 by married physicians Carl and Gerty Cori, who received the 1946 Nobel Prize in Medicine for their eponymous discovery. Explain how glucose can be consumed by muscles, leaching out lactate in the process. The liver then uses this lactate to create glucose, all entirely through enzymatic reactions.
Muscles normally combine glucose with oxygen to generate energy. If oxygen is not available, the anaerobic breakdown of glucose is accomplished through a fermentation process called glycolysis. One of its byproducts is lactate, a soluble milk acid that is excreted back into the bloodstream. Among the many biological functions of the liver is gluconeogenesis, the process by which the body maintains the proper level of blood sugar through the synthesis of glucose from non-carbohydrate components. Critical to completing this cycle is the catalytic coenzyme adenosine triphosphate (ATP).
In the normal presence of oxygen, glycolysis in muscle cells produces two units of ATP and two units of pyruvate, a simple acid that has been implicated as the possible precursor of organic life. The two compounds provide the energy that allows a cell to perpetuate respiration through a series of chemical reactions called the Krebs cycle, also called the citric acid or tricarboxylic acid cycle. Oxidation removes one carbon atom and two hydrogen atoms, water and carbon dioxide, from the equation. The 1953 Nobel Prize was awarded to the biochemist who mapped and named this cyclical process.
In the absence of oxygen, organic enzymes can break down glucose carbohydrates by fermentation. Plant cells convert pyruvate to alcohol; A dehydrogenase enzyme in muscle cells converts it to lactate and the amino acid alanine. The liver filters lactate from the blood to reverse engineer it into pyruvate and then glucose. Although less efficient than the Cori cycle, the liver is also capable of recycling alanine back into glucose, plus the waste compound urea, in a process called the alanine cycle. In any case of gluconeogenesis, sugar returns through the bloodstream to meet the high energy demands of muscle cells.
As with most natural cycles, the Cori cycle is not a completely closed cycle. For example, while glycolysis in muscle produces two ATP molecules, glycogen costs the liver six ATP molecules to fuel the cycle. Similarly, the Cori cycle has nowhere to start without the initial insertion of two oxygen molecules. Eventually, the muscles, not to mention the rest of the body, need a new supply of oxygen and glucose.
The physiological demands of vigorous exercise rapidly engage the Cori cycle to burn and recreate glucose anaerobically. When energy demand exceeds the liver’s ability to convert lactate to glucose, a condition called lactic acidosis can occur. Excess lactic acid lowers blood pH to a level that damages tissues, and distressing symptoms will include profound hyperventilation, vomiting, and abdominal cramps. Lactic acidosis is the underlying cause of rigor mortis. Since the body is no longer breathing, all of its muscles continue to consume glucose through the uninterrupted repetition of the Cori cycle.
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