ROS production is low. Consequently aconitase, NADH dehydrogenases, glutamate dehydrogenase and glutamine synthetase are reactivated, whereas glutaminase and proline oxidase are inactivated. These enzymatic alterations lead to an inhibition of the glutaminolytic pathway. Acetyl-CoA, which derives from glycolytic pyruvate and ketone bodies, is converted to a-keto and released as glutamate, proline and glutamine. The truncation of the citrate cycle has the following advantages for the tumor cells: - glutamine, the metabolic source for glutaminolysis is available in high concentrations in all tissues - optimal adaption to extreme fluctuations in oxygen supply - acetyl-CoA is not infiltrated into the citrate cycle and is saved for de novo synthesis of fatty acids and cholesterol.
- hydrogen is released as glutamate, proline and glutamine as well as fatty acids which are less acidic than lactate. - glutaminolysis is less sensitive to superoxide radicals.
Consequences for the citrate cycle under physiological pO2 |
