During ischemia-reperfusion injury, the xanthine oxidase pathway generates reactive oxygen species. Which substrate is most directly oxidized by xanthine oxidase to generate superoxide?

• A NADH
• B Arachidonic acid
• C Hypoxanthine ✓
• D Myeloperoxidase

Explanation

During ischemia, ATP is catabolized to hypoxanthine, and hypoxanthine accumulates due to lack of oxygen as the terminal electron acceptor. Xanthine dehydrogenase is simultaneously converted to xanthine oxidase by calcium-activated proteases. Upon reperfusion, oxygen becomes available and xanthine oxidase oxidizes hypoxanthine (and xanthine) using molecular oxygen as the electron acceptor, generating superoxide (O2·−) and hydrogen peroxide. This burst of reactive oxygen species at reperfusion damages mitochondria, lipid membranes, and proteins, paradoxically worsening injury. NADH oxidase and myeloperoxidase are separate ROS-generating systems.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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