In cancer cells exhibiting the Warburg effect, glucose is preferentially converted to lactate even in the presence of oxygen. Which molecular alteration most directly drives this aerobic glycolysis phenotype?

• A Loss of hexokinase activity leading to glucose-6-phosphate accumulation
• B Deficiency of pyruvate dehydrogenase complex causing pyruvate to enter the TCA cycle
• C Overexpression of GLUT transporters and glycolytic enzymes, with altered pyruvate kinase (M2 isoform) regulation ✓
• D Upregulation of gluconeogenic enzymes causing futile cycling

Explanation

The Warburg effect is driven by overexpression of GLUT transporters and glycolytic enzymes, along with expression of the PKM2 isoform that can be regulated to slow pyruvate production, diverting intermediates to biosynthesis. Option B is incorrect because PDH deficiency would reduce TCA flux, not explain lactate production. Options A and D are not features of the Warburg effect.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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