The glutaminolytic pathway
Glutaminolysis partially recruits reaction steps from theReaction steps from glutamine to α-ketoglutarate
The conversion of the amino acid glutamine to α-ketoglutarate takes place in two reaction steps: 1. Hydrolysis of the amino group of glutamine yielding glutamate and ammonium. Catalyzing enzyme:Recruited reaction steps of the citric acid cycle and malate aspartate shuttle
*α-ketoglutarate + NAD+ + CoASH → succinyl-CoA + NADH+H+ + CO2 catalyzing enzyme: α-ketoglutarate dehydrogenase complex *succinyl-CoA + GDP + Pi → succinate + GTP catalyzing enzyme: succinyl-CoA-synthetase, EC 6.2.1.4 *succinate + FAD → fumarate + FADH2 catalyzing enzyme:Reaction steps from malate to pyruvate and lactate
The conversion of malate to pyruvate and lactate is catalyzed by *NAD(P) dependent malate decarboxylase (malic enzyme; EC 1.1.1.39 and 1.1.1.40) and *Intracellular compartmentalization of the glutaminolytic pathway
The reactions of the glutaminolytic pathway take place partly in the mitochondria and to some extent in the cytosol (compare the metabolic scheme of the glutaminolytic pathway).Glutaminolysis: an important energy source in tumor cells
Glutaminolysis takes place in all proliferating cells, such asEnergy efficacy of glutaminolysis in tumor cells
*one ATP by direct phosphorylation of GDP *two ATP from oxidation of FADH2 *three ATP at a time for the NADH + H+ produced within the α-ketoglutarate dehydrogenase reaction, the malate dehydrogenase reaction and the malate decarboxylase reaction.Advantages of glutaminolysis in tumor cells
*Glutamine is the most abundant amino acid in the plasma and an additional energy source in tumor cells especially when glycolytic energy production is low due to a high amount of the dimeric form of M2-PK. *Glutamine and its degradation products glutamate and aspartate are precursors forSee also
*References
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