Cancer cells preferentially use aerobic glycolysis rather than oxidative phosphorylation even in the presence of adequate oxygen (Warburg effect). Which of the following best explains the metabolic advantage of this strategy for rapidly proliferating cells?

• A Aerobic glycolysis generates more ATP per molecule of glucose than OXPHOS, enabling faster ATP production
• B Aerobic glycolysis avoids ROS generation from the ETC, reducing apoptotic signals
• C Aerobic glycolysis is preferred because it does not require mitochondria, which are dysfunctional in cancer cells
• D Aerobic glycolysis generates biosynthetic precursors (ribose-5-phosphate, NADPH, acetyl-CoA) needed for nucleotide, lipid and amino acid synthesis to support rapid cell division ✓

Explanation

The Warburg effect (aerobic glycolysis) is metabolically inefficient for ATP production (2 ATP per glucose vs. 30–32 via OXPHOS) but provides critical biosynthetic intermediates: glycolytic intermediates feed the pentose phosphate pathway (ribose-5-phosphate for nucleotide synthesis, NADPH for reductive biosynthesis), serine and glycine synthesis, and acetyl-CoA for fatty acid and sterol synthesis. These anabolic substrates are essential for rapidly proliferating cells. ROS avoidance may contribute but is not the primary advantage. Cancer cell mitochondria are generally functional.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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