Arsenate poisoning leads to reduced net ATP production from glycolysis despite continued glucose consumption. Which step is affected and how?
- A Hexokinase is inhibited, blocking glucose-6-phosphate formation
- B Arsenate substitutes for inorganic phosphate at glyceraldehyde-3-phosphate dehydrogenase, and the resulting 1-arseno-3-phosphoglycerate hydrolyzes spontaneously, bypassing the phosphoglycerate kinase ATP-generating step ✓
- C Pyruvate kinase is allosterically inhibited, preventing the final ATP-producing step
- D Enolase is inhibited, preventing phosphoenolpyruvate formation
Correct answer: B. Arsenate substitutes for inorganic phosphate at glyceraldehyde-3-phosphate dehydrogenase, and the resulting 1-arseno-3-phosphoglycerate hydrolyzes spontaneously, bypassing the phosphoglycerate kinase ATP-generating step
Explanation
Arsenate resembles inorganic phosphate and forms a mixed anhydride (1-arseno-3-phosphoglycerate) instead of 1,3-BPG at the glyceraldehyde-3-phosphate dehydrogenase step. This arseno compound is unstable and hydrolyzes non-enzymatically to 3-phosphoglycerate, so the substrate-level phosphorylation catalyzed by phosphoglycerate kinase never occurs. Glycolysis continues to pyruvate, so glucose is consumed but the net ATP yield drops to zero in affected cells. Fluoride and iodide, by contrast, inhibit enolase directly.
Reference: Lehninger Principles of Biochemistry, 8th ed.
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