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Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00424a003· OSTI ID:6208722
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Previous studies have shown that murine macrophages immunostimulated with interferon ..gamma.. and Escherichia coli lipopolysaccharide synthesize NO/sub 2//sup -/, NO/sub 3//sup -/, and citrulline from L-arginine by oxidation of one of the two chemically equivalent guanido nitrogens. The enzymatic activity for this very unusual reaction was found in the 100,000g supernatant isolated from activated RAW 264.7 cells and was totally absent in unstimulated cells. This activity requires NADPH and L-arginine and is enhanced by Mg/sup 2 +/. When the subcellular fraction containing the enzyme activity was incubated with L-arginine, NADPH, and Mg/sup 2 +/, the formation of nitric oxide was observed. Nitric oxide formation was dependent on the presence of L-arginine and NADPH and was inhibited by the NO/sub 2//sup -//NO/sub 3//sup -/ synthesis inhibitor N/sup G/-monomethyl-L-arginine. Furthermore, when incubated with L-(guanido-/sup 15/N/sub 2/)arginine, the nitric oxide was /sup 15/N-labeled. The results show that nitric oxide is an intermediate in the L-arginine to NO/sub 2//sup -/, NO/sub 3//sup -/, and citrulline pathway. L-Arginine is required for the activation of macrophages to the bactericidal/tumoricidal state and suggests that nitric oxide is serving as an intracellular signal for this activation process in a manner similar to that very recently observed in endothelial cells, where nitric oxide leads to vascular smooth muscle relaxation.
Research Organization:
Univ. of Michigan, Ann Arbor (USA)
OSTI ID:
6208722
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:24; ISSN BICHA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
ARGININE
BACTERIA
BIOCHEMICAL REACTION KINETICS
CARBOXYLIC ACIDS
CHALCOGENIDES
CHEMICAL REACTIONS
CONNECTIVE TISSUE CELLS
ESCHERICHIA COLI
GROWTH FACTORS
INTERFERON
ISOTOPES
KINETICS
LIGHT NUCLEI
LYMPHOKINES
MACROPHAGES
MASS SPECTROSCOPY
MICROORGANISMS
MITOGENS
NITRATES
NITRIC OXIDE
NITRITES
NITROGEN 15
NITROGEN COMPOUNDS
NITROGEN ISOTOPES
NITROGEN OXIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDATION
OXIDES
OXYGEN COMPOUNDS
PHAGOCYTES
PROTEINS
REACTION KINETICS
SOMATIC CELLS
SPECTROSCOPY
STABLE ISOTOPES