What is the Cori Cycle?

The Cori cycle describes the linked metabolic pathways by which muscles, even in the absence of oxygen, remain capable of functioning. This occurs as a result of the liver’s ability to convert a muscle’s chemical waste product back into its energy source. 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. It explains how glucose can be consumed by muscles, leaching 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 unavailable, the anaerobic breakdown of glucose is achieved through a fermentation process called glycolysis. One of its by-products 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 blood sugar level through the synthesis of glucose from non-carbohydrate components. Critical to completing this loop is the catalytic co-enzyme 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 to organic life. The two compounds provide the energy that enables 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 pulls a carbon atom and two hydrogen atoms — water and carbon dioxide — out of the equation. The 1953 Nobel Prize was awarded to the biochemist who mapped and named this cyclic process.

In the absence of oxygen, organic enzymes can break down the glucose carbohydrate by fermentation. Plant cells convert pyruvate into an alcohol; a dehydrogenase enzyme in muscle cells converts it into lactate and the amino acid alanine. The liver filters the lactate out of blood to reverse engineer it to pyruvate and then into glucose. Though less efficiently than the Cori cycle, the liver is also capable of recycling the alanine back into glucose, plus the waste compound urea, in a process called the alanine cycle. In either case of gluconeogenesis, the sugar returns through the bloodstream to power the high energy demands of muscle cells.

As with most natural cycles, the Cori cycle is not an entirely closed loop. For example, while two ATP molecules are produced by glycolysis in the muscles, it costs the liver six ATP molecules to feed the cycle by gluconeogenesis. Likewise, the Cori cycle has nowhere to start without the initial insertion of two oxygen molecules. Eventually, muscles, not to mention the rest of the body, need a fresh new supply of both oxygen and glucose.

The physiological demands of vigorous exercise quickly engage the Cori cycle to burn and re-create glucose anaerobically. When the demand for energy exceeds the capacity of the liver to convert lactate to glucose, a condition called lactic acidosis can occur. The excess lactic acid lowers the pH of blood to a tissue damaging level, and symptoms of distress will include deep hyperventilation, vomiting, and abdominal cramping. Lactic acidosis is the underlying cause of rigor mortis. With the body no longer breathing, all its muscles continue consuming glucose through uninterrupted repetition of the Cori cycle.