A patient with Wilson disease accumulates copper in hepatocytes leading to mitochondrial injury and oxidative stress. The primary mechanism of copper-induced free radical generation is:

• A Copper directly activates NADPH oxidase to generate superoxide
• B Fenton-type reaction: Cu+ + H2O2 → Cu2+ + •OH + OH- (hydroxyl radical generation) ✓
• C Copper inhibits catalase increasing steady-state H2O2 levels only
• D Copper substitutes for iron in hemoglobin generating ferryl radicals

Explanation

Copper (and iron) mediate Fenton-type (Haber-Weiss) reactions where the reduced metal ion (Cu+ or Fe2+) reacts with hydrogen peroxide to generate the highly reactive hydroxyl radical (•OH), the most damaging ROS. This explains why copper overload causes mitochondrial lipid peroxidation and DNA damage in Wilson disease. NADPH oxidase is activated by inflammatory signals, not copper directly. Catalase inhibition alone would not generate hydroxyl radicals without the metal-catalyzed reaction.

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

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Written and medically reviewed by the StethoPrep medical team.