Activated macrophages use reactive nitrogen intermediates to kill ingested microbes. Within the phagosome, which reaction generates the principal microbicidal nitrogen species?
- A Arginase converts L-arginine to ornithine, which polymerizes into polyamines toxic to bacteria
- B Nitric oxide synthase converts citrulline to nitric oxide, which nitrates histones
- C Inducible nitric oxide synthase converts L-arginine to nitric oxide, which combines with superoxide to form peroxynitrite ✓
- D Nitric oxide is generated by xanthine oxidase from hypoxanthine and then halogenated by myeloperoxidase
Correct answer: C. Inducible nitric oxide synthase converts L-arginine to nitric oxide, which combines with superoxide to form peroxynitrite
Explanation
After cytokine induction (IFN-gamma with TNF), macrophage iNOS oxidizes the guanidino nitrogen of L-arginine to produce nitric oxide, which reacts with superoxide generated by the phagocyte oxidase to yield peroxynitrite radicals that damage microbial DNA, lipids, and proteins. Citrulline is the co-product, not the substrate, of NOS. Arginase diverts arginine toward polyamine and proline synthesis in alternatively activated macrophages and is anti-microbial-killing.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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