Glutaminolysis

[1][2] Glutaminolysis partially recruits reaction steps from the citric acid cycle and the malate-aspartate shuttle.

The conversion of the amino acid glutamine to α-ketoglutarate takes place in two reaction steps: 1.

[4] In tumor cells the citric acid cycle is truncated due to an inhibition of the enzyme aconitase (EC 4.2.1.3) by high concentrations of reactive oxygen species (ROS)[5][6] Aconitase catalyzes the conversion of citrate to isocitrate.

On the other hand, tumor cells over express phosphate dependent glutaminase and NAD(P)-dependent malate decarboxylase,[7][8][9][10] which in combination with the remaining reaction steps of the citric acid cycle from α-ketoglutarate to citrate impart the possibility of a new energy producing pathway, the degradation of the amino acid glutamine to glutamate, aspartate, pyruvate CO2, lactate and citrate.

High extracellular glutamine concentrations stimulate tumor growth and are essential for cell transformation.

Conversion of glutamine to α-ketoglutarate
The glutaminolytic pathway. Figure legend: blue color = reaction steps of the citric acid cycle; brown color = reaction steps of the malate aspartate shuttle; green color = enzymes overexpressed in tumors. 1 = glutaminase, 2 = GOT, 3 = α-ketoglutarate dehydrogenase, 4 = succinate dehydrogenase, 5 = fumarase, 6 = malate dehydrogenase, 7a = cytosolic malic enzyme, 7b = mitochondrial malic enzyme, 8 = citrate synthase, 9 = aconitase, 10 = lactate dehydrogenase