Metabolism
Pasteur effect
The normal response of cells to restrain glycolysis in the presence of adequate oxygen.
Pasteur effect is the normal physiological mechanism by which oxygen suppresses glycolysis, preventing the conversion of glucose to lactic acid. In the presence of adequate oxygen, cells restrain fermentation and instead oxidize glucose to carbon dioxide. Peat described this as a logical control system in which respiration limits glycolysis to the rate that allows its product to be consumed oxidatively.
The failure of the Pasteur effect constitutes a respiratory defect that Otto Warburg identified as central to cancer. When the effect fails, cells exhibit aerobic glycolysis—the continued production of lactic acid even in the presence of oxygen—which Warburg considered a reversion to a primitive form of life. Peat argued that this defect consists largely of the failure to produce carbon dioxide in the mitochondria, and that lactic acid itself may be the cause of the respiratory defect in cancer, acting as an irritant that shifts the cell further away from oxygen use. Szent-Györgyi contributed the insight that something keeps the cancer cell in an excited state, preventing it from turning off the excitatory process even when oxygen is present.
Estrogen is known to lower the Pasteur effect, partly through an apparent oxygen-wasting effect of an estrogen-activated NADH oxidase function of peroxidase. This enzyme activity is stimulated by estradiol within two hours, before net protein synthesis can be detected, and the resulting reduction in oxygen tension would help account for the shift away from oxidative metabolism. The diversion of pyruvate to oxaloacetate under estrogen's influence would also tend to inhibit succinic dehydrogenase, further compromising respiration.
The Pasteur effect is often contrasted with the Crabtree effect, the inhibition of cellular respiration by an excess of glucose. While the Pasteur effect is a normal regulatory system, the Crabtree effect tends to lower cellular energy and adaptability, and Peat considered it a maladaptive process that becomes a very general phenomenon during stress, when respiration is shut down while glycolysis is activated. On the organismic level, Peat saw the respiratory derangement of hyperventilation—driven by excess lactic acid and leading to edema, vascular leakiness, and multiple organ failure—as analogous to a systemic Crabtree effect. The Randle effect, the inhibition of glucose oxidation by an excess of fatty acids, represents another related metabolic disturbance that lowers efficiency and is promoted by estrogen.
People also ask
- How does the Pasteur effect normally regulate glucose metabolism?Peat described it as a control system where respiration limits glycolysis so that its product can be consumed oxidatively, with oxygen suppressing the conversion of glucose to lactic acid.
- What happens when the Pasteur effect fails in cancer?The failure constitutes a respiratory defect leading to aerobic glycolysis, and Peat argued that the resulting lactic acid may itself cause further respiratory damage by acting as an irritant.
- How does the Pasteur effect differ from the Crabtree effect?The Pasteur effect is a normal regulatory system where oxygen suppresses glycolysis, while the Crabtree effect is a maladaptive inhibition of respiration by excess glucose that Peat considered a stress phenomenon.