Q.40 Which one of the following amino acids is catalyzed by activated macrophages to produce
reactive nitrogen species?
(A) Arginine (B) Asparagine (C) Cysteine (D) Histidine
Activated macrophages catalyze arginine to produce reactive nitrogen species through inducible nitric oxide synthase (iNOS). This process generates nitric oxide (NO) and citrulline, key for antimicrobial defense. The correct answer is (A) Arginine.
Correct Answer
Arginine (A) serves as the substrate for iNOS in classically activated (M1) macrophages, converting L-arginine to NO and L-citrulline via a two-step oxygenation process requiring O₂, NADPH, and cofactors like BH₄. This generates reactive nitrogen species (RNS) such as NO, peroxynitrite (ONOO⁻), and nitroso compounds, aiding pathogen killing and inflammation.
Option Explanations
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Arginine (A) – Correct: Inducible NOS (NOS2/iNOS) in LPS/IFN-γ-stimulated macrophages metabolizes arginine to NO, driving RNS production for microbicidal activity. A citrulline-NO cycle recycles byproducts for sustained output.
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Asparagine (B) – Incorrect: Asparagine supports protein synthesis and ammonia detoxification but plays no direct role in RNS generation by macrophages.
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Cysteine (B) – Incorrect: Cysteine contributes to glutathione synthesis for redox balance and can undergo S-nitrosylation by RNS, but macrophages do not catalyze it to produce RNS.
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Histidine (D) – Incorrect: Histidine forms part of the NOS active site and buffers pH, yet it is not the primary substrate catalyzed for RNS output in activated macrophages.
Biological Mechanism
In M1 macrophages, arginine competes between NOS (pro-inflammatory, RNS-producing) and arginase (anti-inflammatory, ornithine/urea path). Cytokine activation upregulates iNOS, prioritizing RNS for immune response, with implications in infections, autoimmunity, and cancer. This pathway highlights arginine’s dual metabolic role in macrophage polarization.
