Warburg effect in tumor cells refers to preferential use of aerobic glycolysis. The molecular driver most responsible is upregulation of which enzyme isoform?

• A Pyruvate dehydrogenase
• B Succinate dehydrogenase
• C Isocitrate dehydrogenase 2
• D Pyruvate kinase M2 (PKM2) ✓

Explanation

PKM2, the embryonic isoform re-expressed in tumors, has lower activity than PKM1, creating a bottleneck that diverts glycolytic intermediates into biosynthetic pathways needed for rapid proliferation. This low-activity isoform allows accumulation of upstream metabolites for nucleotide, lipid, and amino acid synthesis while producing lactate even with adequate oxygen — the Warburg phenotype. Pyruvate dehydrogenase would direct pyruvate into the TCA cycle rather than lactate. Succinate dehydrogenase and IDH2 are TCA cycle enzymes not primary drivers of aerobic glycolysis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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