The "Cori cycle"


An early breakthrough in their research came with the discovery of the "Cori cycle." This discovery stemmed from their research into the question of what regulates blood glucose concentration and how the human body metabolizes sugar. It was known at the time that faulty sugar metabolism may lead to diabetes, and it was also known that insulin kept the disease in check. The effect of insulin on blood sugar levels had been observed, but scientists did not understand the biochemical mechanism behind insulin's effect.

Sugar metabolism supplies energy for life's activities. The human body is unable to make the slightest muscular movement without the burning of sugar. In the 19th century, the great French physiologist, Claude Bernard, discovered glycogen, the starch-like substance found in muscles and the liver. Glycogen molecules contain glucose, and when needed the glycogen is processed by the body into glucose. This mechanism keeps the glucose level in the blood constant even though the supply is uneven.

The interplay between glucose and glycogen is at the heart of what is known as the "Cori cycle." The Coris found that insulin increased the oxidation of glucose and its conversion to glycogen in muscle, as well as in the liver. Epinephrine, or adrenaline, worked in reverse, decreasing muscle glycogen and liver glycogen. Since other researchers had established that muscle glycogen does not contribute significantly to blood glucose, the Coris concluded that muscle glycogen must form an intermediate substance which then circulates through the blood to the liver. The Coris theorized - and eventually demonstrated - that this intermediate was lactic acid and was integral to the "cycle of carbohydrates," or the "Cori cycle," which they depicted in 1929:2


The Cori Cycle

In 1931 Carl Cori wrote a review article in Physiological Reviews, which summarized what was then known about mammalian carbohydrate metabolism. He observed that most research to date had been done on whole animals and very little on tissue preparations. Studying whole animals had led to advances in understanding regulatory processes but had yielded little knowledge regarding underlying metabolic mechanisms. In his autobiography, Carl Cori notes it was "this realization that led us to examine the potentialities of tissue preparation" which he called "a most exciting period in biochemistry."3 The1931 article appeared on the eve of the Coris move to Washington University: it gave an indication of the direction of their future research on the mechanism of glycogen metabolism, more properly known as glycogenolysis.



1 My discussion of the "Cori cycle" leans heavily on the following: Mildred Cohn, "Carl Ferdinand Cori, Biographical Memoirs of the National Academy of Sciences 61 (1992): 79-109; Joseph Larner, "Gerty Teresa Cori," Ibid., 111-135; Philip Randle, "Carl Ferdinand Cori," Biographical Memoirs of the Fellows of the Royal Society 32 (1986): 67-95.
2 Carl and Gerty Cori, "Glycogen formation in the liver with d- and l-lactic acid," Journal of Biological Chemistry 81 (1929): 402.
3 Carl F. Cori, "The Call of Science," Annual Review of Biochemistry 38 (1969): 14.


 

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European backgrounds | A truly collaborative relationship | The "Cori cycle"
Washington University, the "Cori ester," and the synthesis of glycogen | The final years
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