The 2007 ESPEN Sir David Cuthbertson Lecture: Amino acids between and within organs. The glutamate-glutamine-citrulline-arginine pathway

Deutz, N.E.P.

doi:10.1016/j.clnu.2008.03.010

Cited by 56 publications

(44 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After entering the circulation, Cit is transported to the kidneys where it is converted to arginine (Arg) in human [129,130]. About 80-90% of Cit is derived from Gln in the gut, and about 15% of Arg appearance is via the conversion of Cit in the kidneys [131,132]. Citrulline is the precursor of Arg [133].…”

Section: Effects Of the Combination Of Ala Cit And Pro On • Oh-inducmentioning

confidence: 99%

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Jiang

Liu

et al. 2016

Free Radical Biology and Medicine

View full text Add to dashboard Cite

a b s t r a c tThe present study explored the apoptosis pathways in hydroxyl radicals ( • OH)-induced carp erythrocytes. Carp erythrocytes were treated with the caspase inhibitors in physiological carp saline (PCS) or Ca 2 þ -free PCS in the presence of 40 μM FeSO 4 /20 μM H 2 O 2 . The results showed that the generation of reactive oxygen species (ROS), the release of cytochrome c and DNA fragmentation were caspase-dependent, and Ca 2 þ was involved in calpain activation and phosphatidylserine (PS) exposure in • OH-induced carp erythrocytes. Moreover, the results suggested that caspases were involved in PS exposure, and Ca 2 þ was involved in DNA fragmentation in • OH-induced fish erythrocytes. These results demonstrated that there might be two apoptosis pathways in fish erythrocytes, one is the caspase and cytochrome c-dependent apoptosis that is similar to that in mammal nucleated cells, the other is the Ca 2 þ -involved apoptosis that was similar to that in mammal non-nucleated erythrocytes. So, fish erythrocytes may be used as a model for studying oxidative stress and apoptosis in mammal cells. Furthermore, the present study investigated the effects of glutamine (Gln)'s metabolites [alanine (Ala), citrulline (Cit), proline (Pro) and their combination (Ala 10 Pro 4 Cit 1 )] on the pathways of apoptosis in fish erythrocytes. The results displayed that Ala, Cit, Pro and Ala 10 Pro 4 Cit 1 effectively suppressed ROS generation, cytochrome c release, activation of caspase-3, caspase-8 and caspase-9 at the physiological concentrations, prevented Ca 2 þ influx, calpain activation, PS exposure, DNA fragmentation and the degradation of the cytoskeleton and oxidation of membrane and hemoglobin (Hb) and increased activity of anti-hydroxyl radical (AHR) in • OH-induced carp erythrocytes. Ala 10 Pro 4 Cit 1 produced a synergistic effect of inhibited oxidative stress and apoptosis in fish erythrocytes. These results demonstrated that Ala, Cit, Pro and their combination can protect mammal erythrocytes and nucleated cells against oxidative stress and apoptosis. The studies supported the use of Gln, Ala, Cit and Pro as oxidative stress and apoptosis inhibitors in mammal cells and the hypothesis that the inhibited effects of Gln on oxidative stress and apoptosis are at least partly dependent on that of its metabolites in mammalian.

show abstract

Section: Effects Of the Combination Of Ala Cit And Pro On • Oh-inducmentioning

confidence: 99%

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Jiang

Liu

et al. 2016

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

“…Their work revealed that citrulline was one of the many compounds generated by the metabolism of glutamine in the small intestine. Since then, glutamine has been considered the main precursor for citrulline synthesis (10,15,36), and tracer studies utilizing L- [2-15 N](amino) glutamine seem to indicate that 60 -80% of citrulline originates from glutamine (4,5,23,24). Furthermore, some researchers have shown that glutamine supplementation increases citrulline production or plasma concentration (20,36,40,59) or, conversely, that glutamine depletion reduces citrulline concentration (39).…”

mentioning

confidence: 99%

“…Furthermore, some researchers have shown that glutamine supplementation increases citrulline production or plasma concentration (20,36,40,59) or, conversely, that glutamine depletion reduces citrulline concentration (39). For these reasons, the case for glutamine as the main precursor for citrulline synthesis has become accepted in the literature (10). Citrulline supplementation has been used to reduce blood pressure (13), as part of a full-spectrum antioxidant therapy (30), or to increase protein deposition in a model of aging (35).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Glutamine: precursor or nitrogen donor for citrulline synthesis?

Marini

Didelija

Castillo

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Although glutamine is considered the main precursor for citrulline synthesis, the current literature does not differentiate between the contribution of glutamine carbon skeleton vs. nonspecific nitrogen (i.e., ammonia) and carbon derived from glutamine oxidation. To elucidate the role of glutamine and nonspecific nitrogen in the synthesis of citrulline, L-[2-15 N]-and L-[5-15 N]glutamine and 15 N-ammonium acetate were infused intragastrically in mice. The amino group of glutamine labeled the three nitrogen groups of citrulline almost equally. The amido group and ammonium acetate labeled the ureido and amino groups of citrulline, but not the ␦-nitrogen. D5-glutamine also infused in this arm of the study, which traces the carbon skeleton of glutamine, was utilized poorly, accounting for only 0.2-0.4% of the circulating citrulline. Dietary glutamine nitrogen (both N groups) incorporation was 25-fold higher than the incorporation of its carbon skeleton into citrulline. To investigate the relative contributions of the carbon skeleton and nonspecific carbon of glutamine, arginine, and proline to citrulline synthesis, U-13 Cn tracers of these amino acids were infused intragastrically. Dietary arginine was the main precursor for citrulline synthesis, accounting for ϳ40% of the circulating citrulline. Proline contribution was minor (3.4%), and glutamine was negligible (0.4%). However, the glutamine tracer resulted in a higher enrichment in the ureido group, indicating incorporation of nonspecific carbon from glutamine oxidation into carbamylphosphate used for citrulline synthesis. In conclusion, dietary glutamine is a poor carbon skeleton precursor for the synthesis of citrulline, although it contributes both nonspecific nitrogen and carbon to citrulline synthesis. arginine; proline; urea cycle THE CENTRAL ROLE OF THE SMALL INTESTINE in the metabolism of glutamine was firmly established by the studies of Windmueller and Spaeth (56) using isolated perfused small intestinal preparations. Their work revealed that citrulline was one of the many compounds generated by the metabolism of glutamine in the small intestine. Since then, glutamine has been considered the main precursor for citrulline synthesis (10,15,36), and tracer studies utilizing L-[2-15 N](amino) glutamine seem to indicate that 60 -80% of citrulline originates from glutamine (4,5,23,24).

show abstract

“…The majority of the citrulline is converted to arginine in the kidney, but only about 15 % of the apparent arginine is via this route. Plasma arginine levels can be affected under special conditions in which the disposal capacity of arginine is enhanced, and it was reported that the reduction in plasma arginine level in sepsis was caused by a reduced citrulline to arginine conversion coupled with a decreased citrulline production [3].…”

Section: Dear Editormentioning

confidence: 99%

A randomized trial of intravenous glutamine supplementation in trauma ICU patients: response to the comments by Ozcelik et al.

et al. 2014

View full text Add to dashboard Cite

The 2007 ESPEN Sir David Cuthbertson Lecture: Amino acids between and within organs. The glutamate-glutamine-citrulline-arginine pathway

Cited by 56 publications

References 31 publications

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Glutamine: precursor or nitrogen donor for citrulline synthesis?

A randomized trial of intravenous glutamine supplementation in trauma ICU patients: response to the comments by Ozcelik et al.

Contact Info

Product

Resources

About