Tumor cells growing rapidly in well-oxygenated culture continue to consume large amounts of glucose and secrete lactate rather than fully oxidizing pyruvate in mitochondria. Which single enzymatic adaptation best accounts for the sustained flux of carbon through this fermentative pathway despite abundant oxygen?

• A Overexpression of the mitochondrial glycerol-3-phosphate shuttle
• B Increased activity of pyruvate dehydrogenase kinase, which phosphorylates and inhibits pyruvate dehydrogenase
• C Markedly increased expression of lactate dehydrogenase A, maintaining NAD+ regeneration in the cytosol ✓
• D Activation of the malate-aspartate shuttle, accelerating NADH transfer into mitochondria

Explanation

The Warburg effect reflects high glycolytic flux with conversion of pyruvate to lactate by upregulated LDH-C, regenerating cytosolic NAD+ so glycolysis continues unchecked. This supplies biosynthetic intermediates such as ribose-5-phosphate and 3-phosphoglycerate for rapidly dividing cells. Inhibiting pyruvate dehydrogenase (option B) would reduce oxidative metabolism but does not by itself explain the high lactate output that defines aerobic glycolysis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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