Metronidazole requires anaerobic or microaerophilic conditions for activation. The electron acceptor that reductively activates metronidazole's nitro group in susceptible anaerobes is:

• A Xanthine oxidase reducing the nitro group in aerobic conditions
• B Cytochrome P450 reductase in anaerobic microsomes
• C NADH dehydrogenase (Complex I) of the anaerobic electron transport chain
• D Pyruvate:ferredoxin oxidoreductase (PFOR) transferring electrons via ferredoxin to the nitro group ✓

Explanation

In anaerobic organisms, pyruvate:ferredoxin oxidoreductase (PFOR) oxidises pyruvate to acetyl-CoA, generating low-potential electrons that reduce ferredoxin to a radical anion. This highly reducing ferredoxin then donates an electron to the nitro group of metronidazole, generating a cytotoxic nitro radical anion. This reactive intermediate causes single- and double-strand DNA breaks and oxidative damage to DNA, proteins, and membranes, killing the organism. In aerobic conditions, oxygen acts as the terminal electron acceptor, preventing nitro group reduction — thus aerobic organisms are not susceptible. Metronidazole resistance in Helicobacter pylori involves mutations in rdxA (which encodes an NADPH-nitroreductase, not PFOR) and fdxB.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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