In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 295, No. 6 ( 2008-12), p. E1315-E1322
Abstract:
The amino acid arginine is the sole precursor for nitric oxide (NO) synthesis. We recently demonstrated that an acute reduction of circulating arginine does not compromise basal or LPS-inducible NO production in mice. In the present study, we investigated the importance of citrulline availability in ornithine transcarbamoylase-deficient spf ash (OTCD) mice on NO production, using stable isotope techniques and C57BL6/J (wild-type) mice controls. Plasma amino acids and tracer-to-tracee ratios were measured by LC-MS. NO production was measured as the in vivo conversion of l-[guanidino- 15 N 2 ]arginine to l-[guanidine- 15 N]citrulline; de novo arginine production was measured as conversion of l-[ureido- 13 C-5,5- 2 H 2 ]citrulline to l-[guanidino- 13 C-5,5- 2 H 2 ]arginine. Protein metabolism was measured using l-[ ring- 2 H 5 ]phenylalanine and l-[ ring- 2 H 2 ]tyrosine. OTC deficiency caused a reduction of systemic citrulline concentration and production to 30–50% ( P 〈 0.001), reduced de novo arginine production ( P 〈 0.05), reduced whole-body NO production to 50% ( P 〈 0.005), and increased net protein breakdown by a factor of 2-4 ( P 〈 0.001). NO production was twofold higher in female than in male OTCD mice in agreement with the X-linked location of the OTC gene. In response to LPS treatment (10 mg/kg ip), circulating arginine increased in all groups ( P 〈 0.001), and NO production was no longer affected by the OTC deficiency due to increased net protein breakdown as a source for arginine. Our study shows that reduced citrulline availability is related to reduced basal NO production via reduced de novo arginine production. Under basal conditions this is probably cNOS-mediated NO production. When sufficient arginine is available after LPS stimulated net protein breakdown, NO production is unaffected by OTC deficiency.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00055.2008
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1477331-4
SSG:
12
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