Large amounts of ROS are produced.
ROS inactivate aconitase, NADH dehydrogenases, glutamate dehydrogenase and glutamine synthetase and activate glutaminase and proline oxidase.
Consequently, glutamine is converted to a-ketoglutarate under the catalyzation of the enzymes glutaminase and glutamate oxaloacetate transaminase.
Alpha-ketoglutarate is further degraded to malate using the remaining active citrate cycle enzymes: alpha-ketoglutarate dehydrogenase, succinyl CoA synthetase, succinate dehydrogenase and fumarase.
Malate is oxidatively decarboxylated to pyruvate under the catalyzation of mitochondrial or cytosolic NAD(P) dependent malate decarboxylase (malic enzyme).
Pyruvate can be converted and excreted as lactate.
The degradation of glutamine to lactate has been termed glutaminolysis.
Another metabolic fate of pyruvate is the degradation to acetyl CoA which serves as a precursor for de novo synthesis of fatty acids or cholesterol.