Warburg hypothesis

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The Warburg hypothesis is a hypothesis on the causes of cancer development . It goes back to the work of the German physiologist Otto Heinrich Warburg in the 1920s. He observed that cancer cells excrete pyruvate as lactic acid ( lactic acid fermentation ) instead of burning it like normal cells in the mitochondria ( citric acid cycle ) to generate energy after the glucose is split into pyruvate ( glycolysis ). This behavior is known as the Warburg effect or “aerobic glycolysis” and is undisputed. However, Warburg concluded that the changes observed were the only cause of cancer development. This hypothesis that he established is considered outdated by the advances in molecular biology research. On the other hand, the importance of lactic acid fermentation for the degenerate cancer cells and possible therapies based on it remain the subject of cancer research.

Warburg effect

Healthy cells gain their energy from glycolysis and the subsequent citric acid cycle in the mitochondria ( respiratory chain ), in which the end product of glycolysis, pyruvate , is metabolized via acetyl-CoA . Oxygen is necessary for the degradation in the citric acid cycle. In the event of a lack of oxygen, the citric acid cycle is omitted and the cell converts pyruvate into lactic acid , which it excretes. Thus, the cell only has glycolysis left to generate energy, which is significantly more inefficient than complete oxidation in the citric acid cycle. If the cell receives enough oxygen again, it produces less lactate and returns to producing energy with the help of the respiratory chain.

Otto Warburg discovered in the 1920s that tumor cells only break down glucose in lactic acid fermentation even if they had enough oxygen for the respiratory chain. This means they have a high consumption of glucose. 50 years later, the term Warburg Effect was coined for this discovery .

hypothesis

Warburg concluded as early as 1924 that the observed disturbance of cell respiration was the cause of the development of cancer. He refined this hypothesis in the 1950s and expanded it to include “distant” and “ultimate” causes, whereby the distant causes include practically all carcinogens , while the last cause is the conversion of the energy metabolism from oxidation to fermentation (i.e. glycolysis without a subsequent citric acid cycle ) be.

rating

Otto Warburg's idea that the cause of cancer was to be found in disturbed mitochondria and a disruption of cell respiration was controversial from the start. He was countered that by no means all cancer cells show an altered glucose metabolism and that his hypothesis ignores findings on genetic changes in cells. Meanwhile, Warburg's hypothesis, which sees the Warburg effect as the driving force behind the development of cancer, has been refuted.

Individual evidence

  1. ^ Robert Allan Weinberg : The biology of cancer . 2nd Edition. Garland Science, New York 2014. p. 53.
  2. ^ Angela M. Otto: Warburg effect (s) —a biographical sketch of Otto Warburg and his impacts on tumor metabolism . In: Cancer & Metabolism . tape 4 , no. 1 , March 8, 2016, ISSN  2049-3002 , doi : 10.1186 / s40170-016-0145-9 , PMID 26962452 , PMC 4784299 (free full text) - ( cancerandmetabolism.com [accessed July 17, 2018]). Robert Allan Weinberg : The biology of cancer . 2nd Edition. Garland Science, New York 2014. p. 53.
  3. ^ Angela M. Otto: Warburg effect (s) —a biographical sketch of Otto Warburg and his impacts on tumor metabolism . In: Cancer & Metabolism . tape 4 , no. 1 , March 8, 2016, ISSN  2049-3002 , doi : 10.1186 / s40170-016-0145-9 , PMID 26962452 , PMC 4784299 (free full text) - ( cancerandmetabolism.com [accessed July 17, 2018]).
  4. ^ Angela M. Otto: Warburg effect (s) —a biographical sketch of Otto Warburg and his impacts on tumor metabolism . In: Cancer & Metabolism . tape 4 , no. 1 , March 8, 2016, ISSN  2049-3002 , doi : 10.1186 / s40170-016-0145-9 , PMID 26962452 , PMC 4784299 (free full text) - ( cancerandmetabolism.com [accessed July 17, 2018]). Robert Allan Weinberg : The biology of cancer . 2nd Edition. Garland Science, New York 2014. p. 53.