The Warburg effect refers to the observation that cancer cells preferentially use aerobic glycolysis even in the presence of oxygen. Which mitochondrial enzyme is characteristically DOWNREGULATED to favour this metabolic shift?

• A Pyruvate dehydrogenase kinase 1 (PDK1) downregulation — actually UPREGULATED in cancer to phosphorylate and inactivate PDH
• B Hexokinase 2 — downregulated to reduce initial glucose phosphorylation
• C Lactate dehydrogenase A (LDHA) — downregulated, reducing lactate production
• D Pyruvate kinase M2 (PKM2) — switched to a less-active dimer form, slowing flux to pyruvate and diverting to biosynthesis ✓

Explanation

In the Warburg effect, cancer cells express the M2 isoform of pyruvate kinase (PKM2) which exists predominantly as an inactive dimer rather than the active tetramer; this creates a bottleneck at the PEP→pyruvate step, allowing upstream glycolytic intermediates to be diverted into nucleotide, amino acid, and lipid biosynthesis supporting rapid proliferation. PDK1 is actually upregulated (not downregulated), inhibiting pyruvate dehydrogenase. LDHA and hexokinase 2 are upregulated in cancer cells.

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

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