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Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling.
Proc Natl Acad Sci U S A. 1996 Oct 15; 93(21):11460-5.PN

Abstract

The rates of whole body nitric oxide (NO) synthesis, plasma arginine flux, and de novo arginine synthesis and their relationships to urea production, were examined in a total of seven healthy adults receiving an L-amino acid diet for 6 days. NO synthesis was estimated by the rate of conversion of the [15N] guanidino nitrogen of arginine to plasma [15N] ureido citrulline and compared with that based on urinary nitrite (NO2-)/nitrate (NO3-) excretion. Six subjects received on dietary day 7, a 24-hr (12-hr fed/12-hr fasted) primed, constant, intravenous infusion of L-[guanidino-15N2]arginine and [13C]urea. A similar investigation was repeated with three of these subjects, plus an additional subject, in which they received L-[ureido-13C]citrulline, to determine plasma citrulline fluxes. The estimated rates (mean +/- SD) of NO synthesis over a period of 24 hr averaged 0.96 +/- 0.1 mumol .kg-1.hr-1 and 0.95 +/- 0.1 mumol.kg-1.hr-1, for the [15N]citrulline and the nitrite/nitrate methods, respectively. About 15% of the plasma arginine turnover was associated with urea formation and 1.2% with NO formation. De novo arginine synthesis averaged 9.2 +/- 1.4 mumol. kg-1.hr-1, indicating that approximately 11% of the plasma arginine flux originates via conversion of plasma citrulline to arginine. Thus, the fraction of the plasma arginine flux associated with NO and also urea synthesis in healthy humans is small, although the plasma arginine compartment serves as a significant precursor pool (54%) for whole body NO formation. This tracer model should be useful for exploring these metabolic relationships in vivo, under specific pathophysiologic states where the L-arginine-NO pathway might be altered.

Authors+Show Affiliations

Laboratory of Human Nutrition, Massachusetts Institute of Technology, Cambridge 02139, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8876157

Citation

Castillo, L, et al. "Whole Body Nitric Oxide Synthesis in Healthy Men Determined From [15N] arginine-to-[15N]citrulline Labeling." Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 21, 1996, pp. 11460-5.
Castillo L, Beaumier L, Ajami AM, et al. Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling. Proc Natl Acad Sci USA. 1996;93(21):11460-5.
Castillo, L., Beaumier, L., Ajami, A. M., & Young, V. R. (1996). Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling. Proceedings of the National Academy of Sciences of the United States of America, 93(21), 11460-5.
Castillo L, et al. Whole Body Nitric Oxide Synthesis in Healthy Men Determined From [15N] arginine-to-[15N]citrulline Labeling. Proc Natl Acad Sci USA. 1996 Oct 15;93(21):11460-5. PubMed PMID: 8876157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling. AU - Castillo,L, AU - Beaumier,L, AU - Ajami,A M, AU - Young,V R, PY - 1996/10/15/pubmed PY - 1996/10/15/medline PY - 1996/10/15/entrez SP - 11460 EP - 5 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 93 IS - 21 N2 - The rates of whole body nitric oxide (NO) synthesis, plasma arginine flux, and de novo arginine synthesis and their relationships to urea production, were examined in a total of seven healthy adults receiving an L-amino acid diet for 6 days. NO synthesis was estimated by the rate of conversion of the [15N] guanidino nitrogen of arginine to plasma [15N] ureido citrulline and compared with that based on urinary nitrite (NO2-)/nitrate (NO3-) excretion. Six subjects received on dietary day 7, a 24-hr (12-hr fed/12-hr fasted) primed, constant, intravenous infusion of L-[guanidino-15N2]arginine and [13C]urea. A similar investigation was repeated with three of these subjects, plus an additional subject, in which they received L-[ureido-13C]citrulline, to determine plasma citrulline fluxes. The estimated rates (mean +/- SD) of NO synthesis over a period of 24 hr averaged 0.96 +/- 0.1 mumol .kg-1.hr-1 and 0.95 +/- 0.1 mumol.kg-1.hr-1, for the [15N]citrulline and the nitrite/nitrate methods, respectively. About 15% of the plasma arginine turnover was associated with urea formation and 1.2% with NO formation. De novo arginine synthesis averaged 9.2 +/- 1.4 mumol. kg-1.hr-1, indicating that approximately 11% of the plasma arginine flux originates via conversion of plasma citrulline to arginine. Thus, the fraction of the plasma arginine flux associated with NO and also urea synthesis in healthy humans is small, although the plasma arginine compartment serves as a significant precursor pool (54%) for whole body NO formation. This tracer model should be useful for exploring these metabolic relationships in vivo, under specific pathophysiologic states where the L-arginine-NO pathway might be altered. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/8876157/Whole_body_nitric_oxide_synthesis_in_healthy_men_determined_from_[15N]_arginine_to_[15N]citrulline_labeling_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8876157 DB - PRIME DP - Unbound Medicine ER -