The Warburg effect in cancer cells refers to preferential aerobic glycolysis over oxidative phosphorylation. Which enzyme, when overexpressed in cancer cells, is a key driver of this phenotype by diverting pyruvate away from the mitochondria?

• A Pyruvate kinase M1 (PKM1)
• B Pyruvate dehydrogenase kinase 1 (PDK1) inactivating PDH ✓
• C Lactate dehydrogenase-B (LDH-B)
• D Phosphoglycerate mutase (PGAM)

Explanation

In the Warburg effect, cancer cells upregulate pyruvate dehydrogenase kinase 1 (PDK1), which phosphorylates and inactivates the pyruvate dehydrogenase complex (PDH). This blocks conversion of pyruvate to acetyl-CoA (and thus entry into the TCA cycle in mitochondria), diverting pyruvate to lactate via LDH-A. Hypoxia-inducible factor-1 (HIF-1) and c-Myc transcriptionally upregulate PDK1, LDH-A, and PKM2. PKM1 (option A) is expressed in normal tissues; cancer cells preferentially express the alternatively spliced PKM2, which has lower pyruvate kinase activity, creating bottlenecks that divert glycolytic intermediates to biosynthetic pathways.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.