Tags

Type your tag names separated by a space and hit enter

Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production.
Am J Physiol Endocrinol Metab 2008; 295(6):E1315-22AJ

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.

Authors+Show Affiliations

Univ. of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18697914

Citation

Luiking, Yvette C., et al. "Reduced Citrulline Availability By OTC Deficiency in Mice Is Related to Reduced Nitric Oxide Production." American Journal of Physiology. Endocrinology and Metabolism, vol. 295, no. 6, 2008, pp. E1315-22.
Luiking YC, Hallemeesch MM, van de Poll MC, et al. Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production. Am J Physiol Endocrinol Metab. 2008;295(6):E1315-22.
Luiking, Y. C., Hallemeesch, M. M., van de Poll, M. C., Dejong, C. H., de Jonge, W. J., Lamers, W. H., & Deutz, N. E. (2008). Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production. American Journal of Physiology. Endocrinology and Metabolism, 295(6), pp. E1315-22. doi:10.1152/ajpendo.00055.2008.
Luiking YC, et al. Reduced Citrulline Availability By OTC Deficiency in Mice Is Related to Reduced Nitric Oxide Production. Am J Physiol Endocrinol Metab. 2008;295(6):E1315-22. PubMed PMID: 18697914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced citrulline availability by OTC deficiency in mice is related to reduced nitric oxide production. AU - Luiking,Yvette C, AU - Hallemeesch,Marcella M, AU - van de Poll,Marcel C, AU - Dejong,Cornelis H C, AU - de Jonge,Wouter J, AU - Lamers,Wouter H, AU - Deutz,Nicolaas E P, Y1 - 2008/08/12/ PY - 2008/8/14/pubmed PY - 2009/2/12/medline PY - 2008/8/14/entrez SP - E1315 EP - 22 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 295 IS - 6 N2 - 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. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/18697914/Reduced_citrulline_availability_by_OTC_deficiency_in_mice_is_related_to_reduced_nitric_oxide_production_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00055.2008?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -