The History of the Krebs Cycle


Hans Adolf Krebs first postulated the citric acid cycle (also known as the Krebs cycle) in 1937. His work built upon the discoveries of biochemists before him. Likewise, his work was an essential piece to understanding the big picture of cellular respiration for the scientists who followed.


  • The Krebs cycle is also known as the tricarboxylic acid (TCA) cycle, in addition to the citric acid cycle. It is the second of three steps in cellular respiration, occurring between glycolysis (the breakdown of glucose into pyruvate) and oxidative phosphorylation (the creation of adenotriphosphate or ATP). The Krebs cycle takes place in the mitochondria of cells and is a vital step in the aerobic creation of ATP, the primary fuel for cellular activity.


  • Before Krebs made his discovery in 1937, far more was known about the anaerobic processes by which the body created energy than the aerobic. Hans Buchner and Eduard Buchner discovered glycolysis, an anaerobic process, accidentally in 1897. During the 1920s and early 1930s, scientists Otto Meyerhof, Gustav Embden, Otto Warburg, and Carl and Gerty Cori played significant roles in describing how cells converted nutrients into energy anaerobically.

    Between 1906 and 1920, Torsten Thunberg took the first steps toward understanding cellular respiration by testing how organic substances were oxidized in animal tissue.


  • Pieces of the puzzle surrounding the middle step of cellular respiration started to come together in the mid-1930s. Albert Szent-Györgyi, in 1935, discovered an animal tissue--pigeon breast muscle--well suited for conducting experiments in cellular respiration. He also revealed that the substances Thunberg observed in his experiments acted partially as catalysts.

    In early 1937, Krebs' team discovered that citrate also acted as a catalyst, while researchers C. Martius and F. Knoop discovered another product of citrate oxidation: ketoglutarate. Between March and June 1937, observations at Krebs' Sheffield laboratory revealed that another product of cellular respiration--oxaloacetate--could combine with pyruvate or other compounds to form citrate, closing the circle.


  • Krebs' work supplied some of the missing pieces to the puzzle of cellular respiration and assembled those pieces to form a more complete picture. His work helped describe how cells produce and use energy. Krebs received the Nobel Prize for Physiology and Medicine in 1953 for his work.


  • The last step in the process of cellular respiration--oxidative phosphorylation--was the next mystery to unravel. In 1937, Herman Kalckar linked ATP to cellular respiration. Soon afterward, Fritz Lipmann revealed that ATP was the cell's main energy source. Peter Mitchell, David E. Green, Paul D. Boyer and John E. Walker have made major contributions to the effort to understand how ATP is created. The research continues today.


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