Oxidation of ammonia and hydroxylamine to nitrate in the rat and <i>in vitro</i>

Saul, Robert L.; Archer, Michael C.

doi:10.1093/carcin/5.1.77

Cited by 29 publications

(7 citation statements)

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“…Our initial investigations of nitrate biosynthesis in rats revealed that an oral dose of ['3N]ammonium acetate could be incorporated into nitrate nitrogen (Wagner et al, 1983a). This has been confirmed in similar experiments by Saul & Archer (1984). Furthermore, the oxidation of NH3 to nitrate has been reported to occur in rat liver in vitro (Dull & Hotchkiss, 1984).…”

Section: Introductionsupporting

confidence: 65%

Nitrate biosynthesis in the rat. Precursor-product relationships with respect to ammonia

Wagner¹,

Moldawer²,

Pomposelli³

et al. 1985

Biochemical Journal

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The endogenous biosynthesis of nitrate in rats was investigated by using 15NH3 administered as a continuous intravenous infusion for as long as 96 h. A comparison of the enrichment of 15N in urinary nitrate after a 24 h infusion revealed that it was 36% of the enrichment of plasma NH3 and about 50% of the enrichment of plasma urea and urinary NH3. Continuous infusion of 15NH3 for 96 h showed that a plateau for the incorporation of NH3 into nitrate is reached by 24 h, whereas the enrichment of urinary NH3 and urea increase during the 96 h. After the infusion of progressively larger doses of 15NH3, the concentration of nitrate synthesized de novo increased. Although there was a significant correlation between plasma 15NH3 concentration and 15NO3- appearance, a given change in plasma NH3 concentration does not produce a direct proportional change in nitrate synthesis. Our findings indicate that NH3 is a quantitatively significant nitrogen precursor for nitrate, but that approx. 50% of nitrate nitrogen is derived from other, as yet unidentified, sources.

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Section: Introductionsupporting

confidence: 65%

Nitrate biosynthesis in the rat. Precursor-product relationships with respect to ammonia

Wagner¹,

Moldawer²,

Pomposelli³

et al. 1985

Biochemical Journal

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“…They also showed through the use of 15N-labeled ammonia that ammonia was incorporated into NO- (12). This finding was supported by subsequent studies, which included in vitro experiments, that suggested the involvement of oxygen radicals in the oxidation (13,14). The Housing and Urine Collection.…”

mentioning

confidence: 61%

Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide.

Stuehr

Marletta

1985

Proc. Natl. Acad. Sci. U.S.A.

963

456

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Escherichia coli lipopolysaccharide (LPS)-induced nitrate biosynthesis was studied in LPS-sensitive C3H/He and LPS-resistant C3H/HeJ mice. Intraperitoneal injection of 15 ,ug ofLPS led to a temporary 5-to 6-fold increase in blood nitrate concentration in the C3H/He strain. Levels of nitrate excreted in the urine were also increased. In contrast, no increase was observed in the C3H/HeJ strain with LPS injections up to 175 ,ug. Furthermore, thioglycolate-elicited peritoneal macrophages from C3H/He, but not from C3H/HeJ mice, produced nitrite (60%) and nitrate (40%) when cultured with LPS (10 jig/ml). T-lymphocyte addition/depletion experiments showed the presence of T cells enhanced this response. However, LPS did not cause nitrite or nitrate production in cultures of spleen lymphocytes from either strain. LPS-induced nitrate synthesis was also observed with nude mice and CBA/N mice, indicating that neither functional T lymphocytes nor LPS-responsive B lymphocytes were required for the response in vivo. This was consistent with the in vitro results showing macrophages alone were competent. Mycobacterium bovis infection of C3H/He and C3H/HeJ mice resulted in a large increase in nitrate production over the course of the infection for both strains, suggesting T-lymphocyte-mediated activation of macrophages as a potent stimulus for nitrate biosynthesis.The synthesis of nitrite is significant in that it can directly participate in the endogenous formation of nitrosamines and may also be involved in some aspect of the chemistry of cytotoxicity.A number of studies have now established that mammals on low nitrate diets excrete more nitrate than they ingest (1-3). At first it was thought that this excess urinary nitrate was the product of intestinal microbial metabolism (1), but subsequent studies with germ-free and conventional rats showed that the process of nitrate biosynthesis was by a mammalian pathway (2). The concern for this process stems from the demonstrated carcinogenicity of nitrosamines (4), the association between exposure to high levels of nitrate (NO-) and stomach cancer (5-8), and the potential for the endogenous formation of nitrosamines by reaction of nitrite derived from nitrate by bacterial reduction (9-11) with endogenous or exogenous amines.Tannenbaum and colleagues (12) Frederick, MD). All mice used were 9-12 weeks old except for the BALB/c and CBA mice, which were 7 and 5 weeks old, respectively.Housing and Urine Collection. Mice were housed three to a cage in Nalgene metabolic cages (Thomas) and were given a nutritionally complete low-nitrate diet (12) and distilled drinking water. The urine from three mice was automatically pooled and collected every 24 hr. The cages were cleaned daily with germicidal soap. In all cases, the amount of nitrate in the urine after a 24-hr collection period for three mice was divided by three and reported as the mean daily nitrate production per mouse. As an additional precaution against infection, nude mice were housed in an isolated cubicle, given sterile...

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“…Nitrite, nitrate, ammonium ion, hydroxylamine, citrulline, or combinations of these potential metabolites in concentrations which could be maximally achieved in the in vitro culture assay (100-500 ,uM) have no inhibitory effect on the replication rate of C. neoformans (Granger, D. L., unpublished data). It is possible that oxygen intermediates generated during nitrogen redox reactions could produce fungistasis (36,37).…”

Section: Discussionmentioning

confidence: 99%

Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.

Granger¹,

Hibbs²,

Perfect³

et al. 1988

J. Clin. Invest.

322

169

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The microbiostatic action of macrophages was studied in vitro employing peritoneal cytotoxic macrophages (CM) from mice acting against Cryptococcus neoformans cultured in Dulbecco's medium with 10% dialyzed fetal bovine serum. Fungistasis was measured using electronic particle counting after lysis of macrophages with detergent.Macrophage fungistasis failed in medium lacking only Larginine. Complete fungistasis was restored by L-arginine; restoration was concentration dependent, maximal at 200 MuM. Deletion of all other essential amino acids did not abrogate fungistasis provided that L-arginine was present. Of twenty guanido compounds, including D-arginine, only three (L-arginine, L-homoarginine, and L-arginine methylester) supported fungistasis. Known activators or mediators of macrophage cytotoxicity (endotoxin, interferon gamma, tumor necrosis factor) did not replace L-arginine for CM-mediated fungistasis. The guanido analogue NG-monomethyl-L-arginine was a potent competitive inhibitor of CM-mediated fungistasis giving 50% inhibition at an inhibitor/L-arginine ratio of 1:27. Although CM completely blocked fungal reproduction via an Larginine-dependent mechanism, the majority of the dormant fungi remained viable. Thus, this mechanism is viewed as a microbiostatic process similar or identical to the tumoristatic effect of macrophages. This suggests the production of a broad spectrum biostatic metabolite(s) upon consumption of L-arginine by cytotoxic macrophages.

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Oxidation of ammonia and hydroxylamine to nitrate in the rat and in vitro

Cited by 29 publications

References 0 publications

Nitrate biosynthesis in the rat. Precursor-product relationships with respect to ammonia

Nitrate biosynthesis in the rat. Precursor-product relationships with respect to ammonia

Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide.

Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.

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