Pathology · Cell Injury, Death and Adaptations (Apoptosis, Necrosis, Free Radicals)

During reperfusion of ischemic myocardium, a burst of reactive oxygen species (ROS) is generated. The enzyme primarily responsible for this reperfusion-associated superoxide burst in cardiomyocytes, distinct from mitochondrial sources, is:

  • A NADPH oxidase (NOX2) at the plasma membrane
  • B Cytochrome P450 reductase
  • C Myeloperoxidase from recruited neutrophils
  • D Xanthine oxidase, via conversion from xanthine dehydrogenase during ischemia
Correct answer: D. Xanthine oxidase, via conversion from xanthine dehydrogenase during ischemia

Explanation

During ischemia, ATP depletion leads to accumulation of hypoxanthine and conversion of xanthine dehydrogenase to xanthine oxidase (via limited proteolysis). Upon reperfusion, oxygen reintroduction allows xanthine oxidase to catalyze oxidation of hypoxanthine/xanthine, generating a burst of superoxide (O2•−) and hydrogen peroxide. This is a key early non-mitochondrial source of reperfusion-injury ROS in cardiomyocytes. Neutrophil myeloperoxidase contributes later in the inflammatory phase.

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

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