Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine release by the liver constitutes a process of nitrogen salvage through the recycling of a part of the nitrogen, which prevents irreversible nitrogen losses as urea. The aim of this work was to study the nitrogen cycling in the splanchnic bed under different nutritional conditions: fed state, postabsorptive state (16 h food deprivation) or prolonged starvation (24 or 40 h). Rats were adapted to a 15% casein diet for 15 d and then sampled. The digestive, hepatic and splanchnic balances of glucose, lactate, ketone bodies, urea and amino acids were determined. There was a net release of lactate and alanine by the digestive tract, due to the high rate of glycolysis and glutaminolysis. During prolonged starvation, ketone bodies became major energy fuel for the intestine. In fed rats, there was a net uptake of most amino acids by the liver, except for glutamine and glutamate. Urea, glutamine and glutamate released represented 33, 24 and 6% of total nitrogen taken up by the liver, respectively. In postabsorptive rats, compared with fed rats, there was a significant reduction of ureagenesis, and glutamine became the major form of nitrogen released by the liver. In fact, nitrogen cycling in the form of glutamine or glutamate in the liver may be interpreted as a nitrogen salvage process, rather than as an acid-base control process. In the splanchnic area, in parallel with a highly active cycling of glucose as lactate, there exists a nitrogen cycling involving opposite fluxes of glutamine and alanine.
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PMID:Opposite fluxes of glutamine and alanine in the splanchnic area are an efficient mechanism for nitrogen sparing in rats. 973 9

Glutamine is the most abundant free amino acid in human muscle and plasma and is utilised at high rates by rapidly dividing cells, including leucocytes, to provide energy and optimal conditions for nucleotide biosynthesis. As such, it is considered to be essential for proper immune function. During various catabolic states including surgical trauma, infection, starvation and prolonged exercise, glutamine homeostasis is placed under stress. Falls in the plasma glutamine level (normal range 500 to 750 mumol/L after an overnight fast) have been reported following endurance events and prolonged exercise. These levels remain unchanged or temporarily elevated after short term, high intensity exercise. Plasma glutamine has also been reported to fall in patients with untreated diabetes mellitus, in diet-induced metabolic acidosis and in the recovery period following high intensity intermittent exercise. Common factors among all these stress states are rises in the plasma concentrations of cortisol and glucagon and an increased tissue requirement for glutamine for gluconeogenesis. It is suggested that increased gluconeogenesis and associated increases in hepatic, gut and renal glutamine uptake account for the depletion of plasma glutamine in catabolic stress states, including prolonged exercise. The short term effects of exercise on the plasma glutamine level may be cumulative, since heavy training has been shown to result in low plasma glutamine levels (< 500 mumol/L) requiring long periods of recovery. Furthermore, athletes experiencing discomfort from the overtraining syndrome exhibit lower resting levels of plasma glutamine than active healthy controls. Therefore, physical activity directly affects the availability of glutamine to the leucocytes and thus may influence immune function. The utility of plasma glutamine level as a marker of overtraining has recently been highlighted, but a consensus has not yet been reached concerning the best method of determining the level. Since injury, infection, nutritional status and acute exercise can all influence plasma glutamine level, these factors must be controlled and/or taken into consideration if plasma glutamine is to prove a useful marker of impending overtraining.
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PMID:Glutamine, exercise and immune function. Links and possible mechanisms. 980 74

The glutamine metabolism was studied in glucose-starved and glucose-sufficient hybridoma and Sp2/0-Ag14 myeloma cells. Glucose starvation was attained by cultivating the hybridoma cells with fructose instead of glucose, and the myeloma cells with a low initial glucose concentration which was rapidly exhausted. Glutamine used in the experiments was labeled with 15N, either in the amine or in the amide position. The fate of the label was monitored by 1H/15N NMR analysis of released 15NH+4 and 15N-alanine. Thus, NH+4 formed via glutaminase (GLNase) could be distinguished from NH+4 formed via glutamate dehydrogenase (GDH). In the glucose-sufficient cells a small but measurable amount of 15NH+4 released by GDH could be detected in both cell lines (0.75 and 0.31 micromole/10(6) cells for hybridoma and myeloma cells, respectively). The uptake of glutamine and the total production of NH+4 was significantly increased in both fructose-grown hybridoma and glucose-starved myeloma cells, as compared to the glucose-sufficient cells. The increased NH+4 production was due to an increased throughput via GLNase (1.6 -1.9-fold in the hybridoma, and 2.7-fold in the myeloma cell line) and an even further increased metabolism via GDH (4.8-7.9-fold in the hybridoma cells, and 3.1-fold in the myeloma cells). The data indicate that both GLNase and GDH are down-regulated when glucose is in excess, but up-regulated in glucose-starved cells. It was calculated that the maximum potential ATP production from glutamine could increase by 35-40 % in the fructose-grown hybridoma cells, mainly due to the increased metabolism via GDH.
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PMID:Elevated glutamate dehydrogenase flux in glucose-deprived hybridoma and myeloma cells: evidence from 1H/15N NMR. 1009 57

Asparagine linked (N-linked) glycosylation is an important modification of recombinant proteins, because the attached oligosaccharide chains can significantly alter protein properties. Potential glycosylation sites are not always occupied with oligosaccharide, and site occupancy can change with the culture environment. To investigate the relationship between metabolism and glycosylation site occupancy, we studied the glycosylation of recombinant human interferon-gamma (IFN-gamma) produced in continuous culture of Chinese hamster ovary cells. Intracellular nucleotide sugar levels and IFN-gamma glycosylation were measured at different steady states which were characterized by central carbon metabolic fluxes estimated by material balances and extracellular metabolite rate measurements. Although site occupancy varied over a rather narrow range, we found that differences correlated with the intracellular pool of UDP-N-acetylglucosamine + UDP-N-acetylgalactosamine (UDP-GNAc). Measured nucleotide levels and estimates of central carbon metabolic fluxes point to UTP depletion as the cause of decreased UDP-GNAc during glucose limitation. Glucose limited cells preferentially utilized available carbon for energy production, causing reduced nucleotide biosynthesis. Lower nucleoside triphosphate pools in turn led to lower nucleotide sugar pools and reduced glycosylation site occupancy. Subsequent experiments in batch and fed-batch culture have confirmed that UDP-sugar concentrations are correlated with UTP levels in the absence of glutamine limitation. Glutamine limitation appears to influence glycosylation by reducing amino sugar formation and hence UDP-GNAc concentration. The influence of nucleotide sugars on site occupancy may only be important during periods of extreme starvation, since relatively large changes in nucleotide sugar pools led to only minor changes in glycosylation.
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PMID:Metabolic effects on recombinant interferon-gamma glycosylation in continuous culture of Chinese hamster ovary cells. 1009 45

Glutamine starvation induces apoptosis in enterocytes; therefore glutamine is important in the maintenance of gut mucosal homeostasis. However, the molecular mechanisms are unknown. The caspase family of proteases constitutes the molecular machinery that drives apoptosis. Caspases are selectively activated in a stimulus-specific and tissue-specific fashion. The aims of this study were to (1) identify specific caspases activated by glutamine starvation and (2) determine whether a general caspase inhibitor blocks glutamine starvation-induced apoptosis in intestinal epithelial cells. Rat intestinal epithelial (RIE-1) cells were deprived of glutamine. Specific caspase activation was measured using fluorogenic substrate assay. Apoptosis was quantified by DNA fragmentation and Hoechst nuclear staining. Glutamine starvation of RIE-1 cells resulted in the time-dependent activation of caspases 3 (10 hours) and 2 (18 hours), and the induction of DNA fragmentation (12 hours). Caspases 1 and 8 remained inactive ZVAD-fluoromethyl ketone, a general caspase inhibitor, completely blocked glutamine starvation-induced caspase activation, DNA fragmentation, and nuclear condensation. These results indicate that glutamine starvation selectively activates specific caspases, which leads to the induction of apoptosis in RIE-1 cells. Furthermore, inhibition of caspase activity blocked the induction of apoptosis, suggesting that caspases are potential molecular targets to attenuate apoptotic responses in the gut.
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PMID:Prevention of mucosal atrophy: role of glutamine and caspases in apoptosis in intestinal epithelial cells. 1105 61

Glutamine is an important fuel for some cells of the immune system. In situations of stress, such as clinical trauma, starvation, or prolonged, strenuous exercise, the concentration of glutamine in blood is decreased, often substantially. In endurance athletes this decrease occurs concomitantly with relatively transient immunodepression. Provision of glutamine or a glutamine precursor has been found to decrease the incidence of illness in endurance athletes. To date, it has not been established precisely which aspect of the immune system is affected by glutamine feeding during the transient immunodepression that occurs after prolonged, strenuous exercise. However, there is increasing evidence that neutrophils may be implicated.
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PMID:Can glutamine modify the apparent immunodepression observed after prolonged, exhaustive exercise? 1198 38

Two-month-old tomato plants were submitted to day/night cycles and to prolonged darkness in order to investigate the physiological and biochemical response to sugar starvation in sink organs. Roots appeared particularly sensitive to the cessation of photosynthesis, as revealed by the reduction of the growth rate and the decline of the carbohydrate and protein content. Therefore, excised tomato roots were used as a model to deepen the characterization of sugar starvation symptoms. In excised roots, the endogenous sugars were rapidly exhausted and significant degradation of protein was observed. Glutamine and asparagine accounted for most of the nitrogen released by protein breakdown. Respiration declined and proliferation- and growth-associated genes were repressed soon after the beginning of the sugar depletion. Among the genes studied, only the gene encoding asparagine synthetase was strongly induced. All the starvation symptoms were reversible when the roots were resupplied with sugar. When the culture conditions deteriorated, the metabolic and molecular changes led to the triggering of apoptosis of the root cells.
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PMID:Physiological, biochemical and molecular analysis of sugar-starvation responses in tomato roots. 1265 65

In situations of stress, such as clinical trauma, starvation or prolonged, strenuous exercise, the concentration of glutamine in the blood is decreased, often substantially. In endurance athletes this decrease occurs concomitantly with relatively transient immunodepression. Glutamine is used as a fuel by some cells of the immune system. Provision of glutamine or a glutamine precursor, such as branched chain amino acids, has been seen to have a beneficial effect on gut function, on morbidity and mortality, and on some aspects of immune cell function in clinical studies. It has also been seen to decrease the self-reported incidence of illness in endurance athletes. So far, there is no firm evidence as to precisely which aspect of the immune system is affected by glutamine feeding during the transient immunodepression that occurs after prolonged, strenuous exercise. However, there is increasing evidence that neutrophils may be implicated. Other aspects of glutamine and glutamine supplementation are also addressed.
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PMID:Glutamine supplementation in vitro and in vivo, in exercise and in immunodepression. 1269 82

1. Aminopterin prevents the multiplication of HeLa cells in Eagle's medium. The joint addition of adenine and thymidine removes the inhibition. 2. The aminopterin-induced thymine deficiency specifically results in a cessation of cell division and a doubling in the average protein content of the cells. Continued starvation for thymine results in the inability of cells to proliferate after aminopterin is removed. After 6 days only 10(-6) to 10(-5) of the original population proliferates. 3. The omission of a single essential amino acid, such as arginine or glutamine, from the medium during deprivation of thymine prevents a net increase in protein and results in about a 10(5)-fold greater cell survival after 6 days, when aminopterin is removed and the missing amino acid is supplied. 4. Glutamine-requiring, auxotrophic mutants of HeLa exhibit a high survival after exposure to aminopterin in a glutamine-free medium. Glutamine-independent HeLa cells show a much lower survival in the same medium. Low frequencies of the auxotrophs can be specifically and efficiently selected for in artificial mixtures of the two cell types by treatment with the glutamine-free medium containing aminopterin.
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PMID:A method of selecting for auxotrophic mutants of HeLa cells. 1372 Jul 2

High intracellular glutamine levels have been implicated in promoting net protein synthesis and accretion in mammalian skeletal muscle. Little is known regarding glutamine metabolism in uricotelic species but chicken breast muscle exhibits high rates of protein accretion and would be predicted to maintain high glutamine levels. However, chicken breast muscle expresses high glutaminase activity and here we report that chicken breast muscle also expresses low glutamine synthetase activity (0.07+/-0.01 U/g) when compared to leg muscle (0.50+/-0.04 U/g). Free glutamine levels were 1.38+/-0.09 and 9.69+/-0.12 nmol/mg wet weight in breast and leg muscles of fed chickens, respectively. Glutamine levels were also lower in dove breast muscle (4.82+/-0.35 nmol/mg wet weight) when compared to leg muscle (16.2+/-1.0 nmol/mg wet weight) and much lower (1.80+/-0.46 nmol/mg wet weight) in lizard leg muscle. In fed chickens, rates of fractional protein synthesis were higher in leg than in breast muscle, and starvation (48 h) resulted in a decrease in both glutamine content and rate of protein synthesis in leg muscle. Thus, although tissue-specific glutamine metabolism in uricotelic species differs markedly from that in ureotelic animals, differences in rates of skeletal muscle protein synthesis are associated with corresponding differences in intramuscular glutamine content.
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PMID:Glutamine metabolism in uricotelic species: variation in skeletal muscle glutamine synthetase, glutaminase, glutamine levels and rates of protein synthesis. 1576 16


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