Which enzyme initiates intracellular killing during the neutrophil respiratory burst?

• A. Catalase
• B. Myeloperoxidase
• C. Superoxide dismutase
• D. NADPH oxidase

Answer: (D)

NADPH oxidase is the driver of the neutrophil respiratory burst. It sits on the phagosomal membrane and transfers electrons from NADPH to oxygen, generating superoxide inside the phagosome. That superoxide starts the cascade of intracellular killing: superoxide is rapidly converted by superoxide dismutase into hydrogen peroxide, which myeloperoxidase then uses to make the potent antimicrobial hypochlorous acid. Catalase can break down hydrogen peroxide, and thus modulate the amount available, but it does not initiate killing. This initiation is why defects in NADPH oxidase lead to the inability to mount an effective respiratory burst, as seen in chronic granulomatous disease.