Q51 — Cancer Cell Metabolism — Aerobic Glycolysis and the Warburg Effect

Theoretical 2 Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license

Bioenergetics & Central Metabolism Overview

In quiescent normal cells, under normal physiological conditions, glucose is aerobically metabolized to pyruvate, most of which is transformed to acetyl-CoA by PDC (Pyruvate Dehydrogenase Complex) (Figure 1a). The resulting Acetyl-CoA enters the tricarboxylic acid cycle (TCA, also Krebs or citric acid cycle) in the mitochondria. In anaerobic microenvironment, pyruvate is almost completely converted to lactate in the cytoplasm and the production of Acetyl-CoA is inhibited. In rapidly growing cancer cells, increased expression of Pyruvate Dehydrogenase Kinases (PDKs) inactivates PDC, and inhibits the conversion of pyruvate to Acetyl-CoA (Figure 1b). Instead, the conversion of pyruvate to lactate is activated, and glycolysis takes place in the cell with high intensity.

Figure 1a. Metabolic pathway of glucose in quiescent normal cells — oxidative phosphorylation dominates, yielding ~36 mol ATP per glucose via the TCA cycle. Figure 1a. Glucose metabolism in quiescent normal cells.

Figure 1b. Metabolic pathway of glucose in proliferating cancer cells — aerobic glycolysis dominates (only ~5% of pyruvate enters the TCA cycle via PDC, inhibited by PDKs), supplemented by glutaminolysis feeding the TCA cycle for anabolic precursors. Figure 1b. Glucose metabolism in proliferating cancer cells.

Use the information and figures to determine whether the following statements are true or false.

A. When the normal cell turns cancerous, it switches its glucose metabolism from oxidative phosphorylation to aerobic glycolysis.

B. Cancer cells undergo alterations in metabolic pathways that enable them to suppress glucose uptake and glycolysis. This leads to stimulation of ATP production in the TCA cycle in normal conditions.

C. In rapidly growing tumors where hypoxia occurs, increased glycolysis can not support sufficient ATP production and bioenergetic homeostasis of cells.

D. In cancer cells, beyond the increase of glycolysis, increased glutaminolysis and fatty acid biosynthesis, generate TCA cycle intermediates, which are often used for anabolic and bioenergetic purposes.

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Question reproduced from IBO 2022, Theoretical Paper 2, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)