Dataset Information

Arginine and ornithine are the main precursors for citrulline synthesis in mice.

ABSTRACT: Recent isotopic tracer studies in mice, piglets, and humans have produced conflicting results as to the main carbon skeleton precursor for citrulline and arginine synthesis. This may be due in part to the different tracers infused and models used to interpret the stable isotope data. Furthermore, previous studies usually investigated a single precursor, which prevented the direct comparison among multiple precursors. To further elucidate the contribution of different precursors to citrulline synthesis, all possible enteral and plasma precursors of citrulline were studied in a mouse model during the postabsorptive and postprandial period using multitracer protocols. In addition, three different models were used to interpret the stable isotope data. The utilization of the classic precursor-product equation, developed for i.v. infused tracers but also used to include i.g. tracers, grossly overestimated the contribution of enteral precursors. Regardless of the model employed, dietary and plasma arginine were the main precursors for citrulline synthesis during feeding and plasma arginine during feed deprivation. The contribution of arginine was directly at the site of citrulline synthesis and through plasma ornithine. The predominant role of arginine and ornithine seen in this study supports the observations in mice, piglets, and humans suggesting that ornithine amino transferase is a pivotal enzyme in this pathway.

SUBMITTER: Marini JC

PROVIDER: S-EPMC3278269 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Arginine and ornithine are the main precursors for citrulline synthesis in mice.

Marini Juan C JC

The Journal of nutrition 20120208 3

Recent isotopic tracer studies in mice, piglets, and humans have produced conflicting results as to the main carbon skeleton precursor for citrulline and arginine synthesis. This may be due in part to the different tracers infused and models used to interpret the stable isotope data. Furthermore, previous studies usually investigated a single precursor, which prevented the direct comparison among multiple precursors. To further elucidate the contribution of different precursors to citrulline syn ...[more]

PMID: 22323761

Similar Datasets

Project description:The use of functional nutrients has been proposed to reduce the occurrence of intrauterine growth retardation in animals at birth in several mammalian species. The objective of this study was to verify the effectiveness of citrulline and N-carbamylglutamate (NCG) dietary supplementation as arginine precursors for mammalian species, and the effects on fetal development through a systematic review. The search for studies was performed during August 2018 in the PubMed, ISI Web of Science, Science Direct, and Scopus databases. The literature search was conducted using "arginine precursor", "citrulline", or "N-carbamylglutamate" as keywords, combined with "gestation", "pregnancy", "fetus", "newborn", or "reproduction". Studies in which arginine precursors were evaluated in gestating mammals and their effects on parameters related to the intrauterine development of the conceptus were selected. Of 1,379 articles, 18 were selected, primarily based on the title and the abstract. Supplementation with NCG (0.5 g to 2 g/kg of feed) increased maternal plasma arginine concentrations in all studies that evaluated this variable. Fetal number increased in 55.56% of the studies that evaluated it, and fetal weight increased in the majority (62.5%) of the studies evaluating this variable. By supplementing citrulline, only fetal weight was improved, with an increase in maternal plasma arginine in 40% of the studies. In conclusion, N-carbamoyl glutamate seems to be an arginine precursor more effective than L-citrulline during gestation; however, both precursors, beside L-Arginine, should be evaluated in similar conditions to confirm the existence of specific particularities such as periods and levels of supplementation, which need to be considered for different species of animals. The supplementation of NCG increases arginine concentrations in maternal plasma, thus improving mammalian reproductive efficiency and fetal development, mainly by promoting higher birth weight.

Project description:L-citrulline and L-arginine supplementation has been shown to have several beneficial effects on the cardiovascular system. Nitric oxide (NO) protects against the progression of atherosclerosis and is synthesized by nitric oxide synthase (NOS), which converts L-arginine (L-Arg) into L-citrulline (L-Cit). Our previous study revealed that chronic administration of a combination of L-Cit and L- Arg has a better therapeutic effect on high cholesterol-induced atherosclerosis in rabbits. We investigated how L-Arg and L-Cit affect endothelial function, aging and atherosclerosis. Following a 3-day stimulation of human umbilical venous endothelial cells (HUVECs) with high glucose (HG: 22 mM) and L-Arg (300 μM), L-Cit (300 μM) or L-Arg plus L-Cit (LALC: each 150 μM) supplementation, endothelial senescence and function were evaluated. These amino acids were also administered to dyslipidemic type 2 diabetic (ZDFM) rats fed a high cholesterol diet. They were fed L-Arg or L-Cit or LALC for four weeks. Aortic senescence was investigated by measuring senescence-associated ß-galactosidase (SA-ß-gal), telomerase activity, DNA damage and p16INK4a protein expression. Only L-Cit and LALC supplementation retarded the HG-induced endothelial senescence, as evaluated by SA-ß-gal activity, a widely used marker of cellular senescence, p16INK4a expression, a senescence-related protein, and DNA damage. Under HG conditions, L-Cit and LCLA restored telomerase activity to levels observed under normal glucose (NG) conditions. Under HG conditions, L-Cit decreased ROS production, as measured by CM-H2DCFDA and the expression of p67phox, a major component of NADPH oxidase. Under HG conditions, L-Cit and LALC increased NO production, as measured by DAF-2AM. Endothelial NO synthase (eNOS) and phosphorylated eNOS were decreased under HG conditions and L-Cit and LALC significantly increased these levels. Arginase 2 protein expression increased under the HG conditions, and L-Cit and LALC significantly attenuated this effect. In ZDFM rats, SA-ß-gal activity was detected on the aortic endothelial surface; however, L-Cit and LALC reduced these levels. L-Cit and LALC both decreased the proportion of senescent cells. Furthermore, treatment with LALC for 4 weeks increased plasma NO production. Therefore conclusively, L-citrulline supplementation rescued NO levels better than L-arginine supplementation by inhibiting ROS production and arginase 2 protein expression. Consequently, L-Cit and LCLA supplementation retaeded HG-induced endothelial senescence.

Dataset Information

Arginine and ornithine are the main precursors for citrulline synthesis in mice.

Publications

Arginine and ornithine are the main precursors for citrulline synthesis in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets