scholarly journals Glutamine metabolism in lymphocytes of the rat

1983 ◽  
Vol 212 (3) ◽  
pp. 835-842 ◽  
Author(s):  
M S M Ardawi ◽  
E A Newsholme

The metabolism of glutamine in resting and concanavalin-A-stimulated lymphocytes was investigated. In incubated lymphocytes isolated from rat mesenteric lymph nodes, the rates of oxygen and glutamine utilization and that of aspartate production were approximately linear with respect to time for 60 min, and the concentrations of adenine nucleotides plus the ATP/ADP or ATP/AMP concentration ratios remained approximately constant for 90 min. The major end products of glutamine metabolism were glutamate, aspartate and ammonia: the carbon from glutamine may contribute about 30% to respiration. When both glucose and glutamine were presented to the cells, the rates of utilization of both substances increased. Evidence was obtained that the stimulation of glycolysis by glutamine could be due, in part, to an activation of 6-phosphofructokinase. Starvation of the donor animal increased the rate of glutamine utilization. The phosphoenolpyruvate carboxykinase inhibitor mercaptopicolinate decreased the rate of glutamine utilization by 28%; the rates of accumulation of glutamate and ammonia were decreased, whereas those of lactate, aspartate and malate were increased. The mitogen concanavalin A increased the rate of glutamine utilization (by about 51%). The rate of [3H]thymidine incorporation into DNA caused by concanavalin A in cultured lymphocytes was very low in the absence of glutamine; it was increased about 4-fold at 1 microM-glutamine and was maximal at 0.3 mM-glutamine; neither other amino acids nor ammonia could replace glutamine.

1985 ◽  
Vol 231 (3) ◽  
pp. 713-719 ◽  
Author(s):  
M S M Ardawi ◽  
E A Newsholme

In incubated colonocytes isolated from rat colons, the rates of utilization O2, glucose or glutamine were linear with respect to time for over 30 min, and the concentrations of adenine nucleotides plus the ATP/ADP or ATP/AMP concentration ratios remained approximately constant for 30 min. Glutamine, n-butyrate or ketone bodies were the only substrates that caused increases in O2 consumption by isolated incubated colonocytes. The maximum activity of hexokinase in colonic mucosa is similar to that of 6-phosphofructokinase. Starvation of the donor animal decreased the activities of hexokinase and 6-phosphofructokinase, whereas it increased those of glucose-6-phosphatase and fructose-bisphosphatase. Isolated incubated colonocytes utilized glucose at about 6.8 mumol/min per g dry wt., with lactate accounting for 83% of glucose removed. These rates were not affected by the addition of glutamine, acetoacetate or n-butyrate, and starvation of the donor animal. Isolated incubated colonocytes utilized glutamine at about 5.5 mumol/min per g dry wt., which is about 21% of the maximum activity of glutaminase. The major end-products of glutamine metabolism were glutamate, aspartate, alanine and ammonia. Starvation of the donor animal decreased the rate of glutamine utilization by colonocytes, which is accompanied by a decrease in glutamate formation and in the maximum activity of glutaminase. Isolated incubated colonocytes utilized acetoacetate at about 3.5 mumol/min per g dry wt. This rate was not markedly affected by addition of glucose or by starvation of the donor animal. When colonocytes were incubated with n-butyrate, both acetoacetate and 3-hydroxybutyrate were formed, with the latter accounting for only about 19% of total ketones produced.


1984 ◽  
Vol 221 (2) ◽  
pp. 471-475 ◽  
Author(s):  
K Brand ◽  
J F Williams ◽  
M J Weidemann

The metabolism of glucose and glutamine in freshly prepared resting and concanavalin A-stimulated rat thymocytes was studied. Concanavalin A addition enhanced uptake of both glucose and glutamine and led to an increase in oxidative degradation of both substrates to CO2. With variously labelled [14C]glucose, it was shown that the pathways of glucose dissimilation were equally stimulated by the mitogen. A disproportionately large percentage of the extra glucose taken up was converted into lactate, but concanavalin A also caused an increase in the oxidation of pyruvate as judged by the enhanced release of 14CO2 from [2-14C]-, [3,4-14C]- and [6-14C]-glucose. Addition of glutamine did not affect glucose metabolism. The major end products of glutamine metabolism by resting and mitogen-stimulated rat thymocytes were glutamate, aspartate, CO2 and NH3. Virtually no lactate was formed from glutamine. Concanavalin A enhanced the formation of all end products except glutamate, indicating that more glutamine was metabolized beyond the stage of glutamate in the mitogen-activated cells. Addition of glucose caused a significant decrease in the rates of glutamine utilization and conversion into aspartate and CO2 in the absence and in the presence of concanavalin A. In the presence of glucose, almost all nitrogen of the metabolized glutamine was accounted for as NH3 released via the glutaminase and/or glutamate dehydrogenase reactions. In the absence of glucose, part (18%) of the glutamine nitrogen was metabolized by the resting and to a larger extent (38%) by the mitogen-stimulated thymocytes via a transaminase or amidotransferase reaction.


1983 ◽  
Vol 210 (2) ◽  
pp. 483-487 ◽  
Author(s):  
D Durozard ◽  
G Baverel

1. The effects of 3-aminopicolinate, a known hyperglycaemic agent in the rat, on glutamine metabolism were studied in isolated dog kidney tubules. 2. 3-Aminopicolinate greatly stimulated glutamine (but not glutamate) removal and glutamate accumulation from glutamine as well as formation of ammonia, aspartate, lactate, alanine and glucose. 3. The increased accumulation of aspartate from glutamine and glutamate, and the inhibition of glucose synthesis from various non-nitrogenous gluconeogenic substrates, as well as the increased accumulation of malate from succinate, support the proposal that 3-aminopicolinate is an inhibitor rather than a stimulator of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in dog kidney tubules. 4. With glutamine as substrate, the increase in flux through glutamate dehydrogenase (EC 1.4.1.3) could not explain the large increase in glutamine removal caused by 3-aminopicolinate. 5. Inhibition by amino-oxyacetate of accumulation of aspartate and alanine from glutamine caused by 3-aminopicolinate did not prevent the acceleration of glutamine utilization. 6. These data are consistent with a direct stimulation of glutaminase (EC 3.5.1.2) by 3-aminopicolinate in dog kidney tubules.


1971 ◽  
Vol 124 (2) ◽  
pp. 265-274 ◽  
Author(s):  
F. J. Ballard

1. Measurements in livers of rats delivered by Caesarian section show a rapid change in the relative proportion of adenine nucleotides. By 20min the ATP/ADP ratio had increased from 1.76 to 8.7 and the value of the relationship [ATP][AMP]/[ADP]2increased from 1.0 to 4.4. These changes are dependent on the availability of oxygen to the animal. 2. The free [NAD+]/[NADH] ratio in the liver cytosol increases from 180 after delivery to reach a maximum of 1010 at 2h, before falling to 540 in the 24h-old animal. 3. The mitochondrial NAD redox potential also shows a sharp increase towards a more oxidized state in livers of delivered rats. 4. These results probably indicate that the foetal liver is hypoxic, with oxygenation occurring in the first hour after delivery. 5. Measurements in livers of naturally born rats 2min after birth also suggest that this tissue is hypoxic with an ATP/ADP ratio of 1.83 and a free [NAD+]/[NADH] ratio of 117. 6. Concentrations of intermediates in the gluconeogenic pathway have been determined in livers of foetal, 1h-old and 1-day-old rats. These experiments imply a facilitation of lactate dehydrogenase and glucose 6-phosphatase activities by 1h after birth, and a stimulation of phosphoenolpyruvate carboxykinase and glucose 6-phosphatase steps by 1 day after birth. 7. The appearance of gluconeogenesis in livers of newborn rats seems therefore to involve an oxygenation stage followed by an increase in phosphoenolpyruvate carboxykinase activity.


1993 ◽  
Vol 165 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Paul S. Dudrick ◽  
Peter Sarantos ◽  
Kimberly Ockert ◽  
Ratna Chakrabarti ◽  
Edward M. Copeland ◽  
...  

1989 ◽  
Vol 261 (3) ◽  
pp. 739-742 ◽  
Author(s):  
Z Szondy ◽  
E A Newsholme

The effect of adenosine on the metabolism of prelabelled adenine nucleotides was investigated in concanavalin-A-stimulated rat lymphocytes. Adenosine in the presence of the adenosine deaminase inhibitor, deoxycoformycin, caused a 2-fold increase in the ATP concentration. This effect was, in part, countereacted by an increased rate of adenine nucleotide catabolism, which could be explained by a stimulation of AMP deaminase (EC 3.5.4.6). At the same time a continuous rate of labelled adenosine production was found, which was not affected by the increased ATP concentration and which could only be detected by the trapping effect of a high concentration of added unlabelled adenosine. It is concluded that the rate of the substrate cycle between AMP and adenosine is low (1.9 +/- 0.2 nmol/h per 10(7) cells) in comparison to the rate of AMP deamination.


mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Michal Werbner ◽  
Yiftah Barsheshet ◽  
Nir Werbner ◽  
Mor Zigdon ◽  
Itamar Averbuch ◽  
...  

How do stressful life events increase the risk for autoimmune disorders? Here we show that chronic social stress in mice promotes the expression of virulent genes in the gut microbiota and alters the microbial translocation into the mesenteric lymph nodes. Our results also suggest that the consequent immune response to the stress-affected microbiota may endanger the tolerance for self. The presence of specific translocated bacteria and the immune response in the mesenteric lymph nodes can be diminished using an inhibitor of the bacterial communication system without drastically affecting the gut microbial composition as antibiotics do.


2002 ◽  
Vol 368 (1) ◽  
pp. 301-308 ◽  
Author(s):  
Agnès CONJARD ◽  
Virginie BRUN ◽  
Mireille MARTIN ◽  
Gabriel BAVEREL ◽  
Bernard FERRIER

It has been shown recently that glutamine is taken up by the mouse kidney in vivo. However, knowledge about the fate of this amino acid and the regulation of its metabolism in the mouse kidney remains poor. Given the physiological and pathophysiological importance of renal glutamine metabolism and the increasing use of genetically modified mice in biological research, we have conducted a study to characterize glutamine metabolism in the mouse kidney. Proximal tubules isolated from fed and 48h-starved mice and then incubated with a physiological concentration of glutamine, removed this amino acid and produced ammonium ions at similar rates. In agreement with this observation, activities of the ammoniagenic enzymes, glutaminase and glutamate dehydrogenase, were not different in the renal cortex of fed and starved mice, but the glutamate dehydrogenase mRNA level was elevated 4.5-fold in the renal cortex from starved mice. In contrast, glucose production from glutamine was greatly stimulated whereas the glutamine carbon removed, that was presumably completely oxidized in tubules from fed mice, was virtually suppressed in tubules from starved animals. In accordance with the starvation-induced stimulation of glutamine gluconeogenesis, the activities and mRNA levels of glucose-6-phosphatase, and especially of phosphoenolpyruvate carboxykinase, but not of fructose-1,6-bisphosphatase, were increased in the renal cortex of starved mice. On the basis of our in vitro results, the elevated urinary excretion of ammonium ions observed in starved mice probably reflected an increased transport of these ions into the urine at the expense of those released into the renal veins rather than a stimulation of renal ammoniagenesis.


2001 ◽  
Vol 120 (5) ◽  
pp. A183-A183
Author(s):  
H KOBAYASHI ◽  
H NAGATA ◽  
S MIURA ◽  
T AZUMA ◽  
H SUZUKI ◽  
...  

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