In ischemia-reperfusion injury, xanthine oxidase contributes to burst reactive oxygen species production during reoxygenation. The critical step converting xanthine dehydrogenase to xanthine oxidase during ischemia involves:

• A Irreversible proteolytic cleavage by calcium-activated calpain
• B Both proteolytic cleavage and thiol oxidation ✓
• C Reversible oxidation of thiol groups on the enzyme
• D Phosphorylation by PKC activated by DAG accumulation

Explanation

During ischemia, cytosolic calcium activates calpain (a cysteine protease), which irreversibly cleaves xanthine dehydrogenase (XD) to xanthine oxidase (XO). Additionally, oxidation of sulfhydryl groups on XD by reactive oxygen species provides a reversible conversion mechanism. Both mechanisms operate simultaneously during ischemia. When oxygen is restored at reperfusion, XO uses molecular oxygen (rather than NAD+) as the electron acceptor, producing superoxide and hydrogen peroxide in large quantities. This ROS burst is a central mechanism of reperfusion injury beyond simple ischemia.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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