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)

The present study was designed to investigate the metabolism of glycylglutamine and its effects on organ balances of amino acids during intravenous infusion of this dipeptide (100 mumol.h-1.kg-1) in postabsorptive and briefly starved (84-86 h) human subjects. Arterial concentrations of glycylglutamine were not significantly different in postabsorptive (265 +/- 18 microM) and starved (241 +/- 13 microM) subjects. Among the organs examined, kidney predominated in clearance of glycylglutamine from plasma. Moreover, renal clearance of glycylglutamine was reduced by starvation (87 +/- 7 vs. 52 +/- 5 mumol/min, P less than 0.01), whereas neither splanchnic nor muscle clearance was significantly affected. Infusion of glycylglutamine raised plasma concentrations of glycine and glutamine by increasing renal release of these amino acids. In postabsorptive subjects the infusion significantly increased splanchnic balances of glycine and glutamine with little or no effect on the muscle balances; the opposite was found in starved subjects. As far as other amino acids are concerned, the infusion decreased the muscle release of alanine and increased renal release of serine. We conclude that the amino acid residues of glycylglutamine are largely metabolized by the splanchnic organs in postabsorptive subjects and by peripheral organs in starved subjects. The latter results in selective inhibition of muscle release of amino acids.
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PMID:Glycylglutamine: metabolism and effects on organ balances of amino acids in postabsorptive and starved subjects. 153 41

Periportal hepatocytes around the afferent vessels and perivenous hepatocytes around the efferent vessels of the liver acinus exhibit different metabolic capacities and subcellular structures. This observation led to the concept of the metabolic zonation of the liver acinus. Oxidative energy metabolism, gluconeogenesis, urea synthesis, bile formation and protective metabolism are catalyzed mainly in the periportal zone; glycolysis linked to liponeogenesis, glutamine synthesis and xenobiotic metabolism are predominant in the perivenous zone. This zonation is dynamic rather than static. Zonation develops gradually, depending on perinatal changes of the hepatic circulation and on postnatal alterations of the supply with energy substrates. Zonation also is modulated during puberty. Moreover, adaptation to longer-lasting physiological and pathological alterations occurs as observed during starvation and refeeding, diabetes and regeneration after partial hepatectomy or zonal necrosis. Periportal to perivenous gradients of oxygen, hormones and metabolites, as well as zonal differences in the hepatic innervation, seem to be responsible for the heterogeneous gene expression within the liver acinus.
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PMID:Metabolic heterogeneity of hepatocytes across the liver acinus. 154 56

Glutamine synthetase activity from Synechocystis sp. strain PCC 6803 is regulated as a function of the nitrogen source available in the medium. Addition of 0.25 mM NH4Cl to nitrate-grown cells promotes a clear short-term inactivation of glutamine synthetase, whose enzyme activity decreases to 5 to 10% of the initial value in 25 min. The intracellular levels of glutamine, determined under various conditions, taken together with the results obtained with azaserine (an inhibitor of transamidases), rule out the possibility that glutamine per se is responsible for glutamine synthetase inactivation. Nitrogen starvation attenuates the ammonium-mediated glutamine synthetase inactivation, indicating that glutamine synthetase regulation is modulated through the internal balance between carbon-nitrogen compounds and carbon compounds. The parallelism observed between the glutamine synthetase activity and the internal concentration of alpha-ketoglutarate suggests that this metabolite could play a role as a positive effector of glutamine synthetase activity in Synechocystis sp. Despite the similarities of this physiological system to that described for enterobacteria, the lack of in vivo 32P labeling of glutamine synthetase during the inactivation process excludes the existence of an adenylylation-deadenylylation system in this cyanobacterium.
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PMID:Regulation of glutamine synthetase activity in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 by the nitrogen source: effect of ammonium. 167 97

Cytoplasmic and mitochondrial molecular forms of glutamine synthetase (CE 6.3.1.2) have been isolated from the carp muscle with purification degree of 100 and 165 times and output 9.0%. It is established that the temperature optimum of the cytoplasmic form activity is 30 degrees C and that of mitochondrial one--20 degrees C; the pH optimum for the both molecular forms is 6.0 and 8.2. The optimal ratio [Me2+] : [ATP] for the isolated form is 2:1; Km (seeming) of the cytoplasmic form in the presence of Mg2+ is 6.0 mM for glutamate, 0.035 for ammonium, for ATP 0.5 and 0.7 for magnesium ions; these values for the mitochondrial form are: 14.3, 0.048, 1.0 and 0.8 mM, respectively. Activity of the both glutamine synthetases with Mg2+ ions is almost by 50% higher than that of glutamine synthetases with Mn2+ ions. Seasonal regularities of the synthesis of molecular glutamine synthetase forms have been established in vivo. Cytoplasmic form is present in the muscles all year round, while mitochondrial one only in winter at low temperature of the environment and fish starvation. Differences in properties and seasonal character of synthesis of molecular glutamine synthetase forms in carp muscles are a result of diversity of their functional role.
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PMID:[Multiple molecular forms of glutamine synthetase in carp muscles]. 167 61

We have studied the regulation of expression of the asparagine synthetase (AS) gene in ts11 cells, a mutant of BHK hamster cells which encodes a temperature-sensitive AS and therefore does not produce endogenous asparagine at 39.5 degrees C. Incubation of ts11 cells at the nonpermissive temperature drastically increases the level of AS mRNA, and the stimulation of AS mRNA expression is effectively suppressed by the addition of asparagine to the medium. We show here that regulation of AS gene expression involves cis-acting elements which are contained in the mRNA as well as in the 5' genomic region. When a plasmid containing the human AS cDNA under the control of the human AS promoter region was stably transfected into ts11 cells, the expression of human AS RNAs was regulated as that of the endogenous hamster transcripts, indicating that this construct contained all cis elements necessary for regulation. Expression of the AS cDNA in ts11 cells under the control of a constitutive foreign promoter was also regulated by the concentration of asparagine, and this regulation required translation. When we introduced by mutagenesis a number of stop codons in the AS cDNA, the mutant mRNAs with short open reading frames were expressed at low levels that were not increased by asparagine deprivation. Inhibition of protein and RNA synthesis also prevented down-regulation of AS mRNA levels by high concentrations of asparagine. In a parallel series of experiments, we showed that an AS DNA fragment including the promoter and first exon can also regulate RNA expression in response to asparagine concentration. Furthermore, similar increases in the levels of AS RNAs are produced not only by asparagine deprivation in ts11 cells but also by deprivation of human and wild-type BHK cells of leucine, isoleucine, or glutamine. Thus, regulation of AS gene expression is a response to amino acid starvation through mechanisms which appear to involve both changes in RNA stability and change in the rates of transcription initiation or elongation.
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PMID:Regulation of asparagine synthetase gene expression by amino acid starvation. 168 98

The response to injury and infection can be viewed as a mobilization of body protein, fat, and carbohydrate stores to ensure normal or above-normal circulating levels of substrate in the absence of dietary intake. The situation does not readily yield to nutritional manipulation, and inappropriate nutritional support can cause additional stress. Artificial nutrition is mainly a form of nutrient administration and not nutrient utilization. Modulation of neurohumoral and wound responses to trauma due to starvation and refeeding has not been delineated. The provision of adequate substrates alone does not necessarily guarantee their efficient use in metabolism. With a clear knowledge of the role of cellular mediators in the pathophysiology of disease, it may be possible to develop more rational therapeutic approaches during critical illness. Determination of appropriate and optimal substrate support through parenteral and enteral nutrition remains of great clinical importance. The clinical application of branched-chain amino acids, dispensable amino acids, acetylated amino acids, dipeptides or tripeptides, cysteine, glutamine, and arginine has been explored in recent years. The idea that lipids are deleterious in sepsis and organ failure should be revised and documented, and recent studies suggest that fish oils as a lipid source may also favorably affect immune responses. Under stressful conditions, total parenteral nutrition can require large amounts of energy at a time when there are marked disturbances in glucose utilization. In this area, the use of nonglucose carbohydrates or oligosaccharides can be appropriate, despite the lack of broad acceptance. Existing conventional substrates should be studied beyond mere provision of energy and metabolic pathway support.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutritional and metabolic support: converging concepts. 180 4

Food is an important stimulus for the growth of gastrointestinal mucosa. Gut structure is influenced by the route of nutrient administration, dietary composition and the availability of specific nutrients. The alterations in intestinal structure and function that occur when enteral nutrition is withheld suggests that the ingestion of food results in physiologic responses that are responsible for the maintenance of gut mass during the fed state. The mechanism of mucosal suppression that occurs during starvation, stress, and total parenteral nutrition is not completely understood but may involve the absence of luminal substrates, decreased pancreaticobiliary secretions and alterations in the endocrine or paracrine events that normally accompany eating, digestion, and absorption. Enterocytes prefer glutamine and ketone bodies as oxidative fuels, whereas colonocytes utilize short chain fatty acids. Although enteral delivery of nutrients is the preferred route for maintenance of intestinal mass, provision of specific nutrients and hormonal stimulation during parenteral alimentation has been shown to be important in maintaining mucosal structure and function. If not adequately maintained, the intestine becomes susceptible to a variety of injuries which may result in impaired ability to digest and absorb nutrients and loss of mucosal barrier function.
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PMID:Influence of nutrient delivery on gut structure and function. 180 12

400 MHz 1H NMR spectroscopy was used to analyze methyl group-containing metabolites in perchloric acid extracts of livers of rats treated with carbon tetrachloride or fed with ethanol-containing liquid diets, and sacrificed with carbon dioxide anoxic euthanasia or pentobarbital euthanasia (with or without 12-18 hour fasting). In all cases, coenzyme A was detected using 1H NMR spectroscopy, but at higher levels for chronic ethanol-treated rats. Propionate was also detected in livers 6 hours after treatment with carbon tetrachloride. The assignments of the 1H NMR resonances in a spectrum of biological origin to these two metabolites have not been previously reported. Another unusual metabolite, 1,2-propanediol, was also observed in dramatically elevated levels in starved rats. The methyl groups for coenzyme A, propionate, and 1,2-propanediol have 1H NMR chemical shifts at 0.73 and 0.87 ppm, 1.18 ppm, and 1.14 ppm (from tetramethylsilane) respectively. In addition to the above mentioned resonances, glutamine, glutamate, proline, acetate, leucine, alanine, lactate, ethanol, beta-hydroxybutyrate, and valine were also observed in the 0.5-2.3 ppm methyl region of the 1H NMR spectra. Biochemical changes were also observed in these latter metabolites. beta-Hydroxybutyrate was increased by chronic ethanol administration; this increase was exacerbated by starvation. Alanine was decreased by chronic ethanol administration. Acetate was increased by chronic ethanol administration except when glycerol was added to the liver or when the rat was starved. We also observed an unassigned triplet at 0.81 ppm, and its appearance seems to be correlated with that of 1,2-propanediol.
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PMID:1H NMR analyses of methyl group-containing metabolites in rat liver extracts--effects of starvation, anoxia, acute glycerol and carbon tetrachloride treatment and chronic ethanol administration on hepatic metabolism. 181 3

Conventional solutions of parenteral nutrients fail to reverse the colonic atrophy caused by starvation. This may be due to the absence from these solutions of the amino acid glutamine--a fuel for rapidly dividing cells such as colonocytes and fibroblasts. Although glutamine is unstable in solution, the infusion of branched chain amino acids (BCAA) increases the rate of synthesis and release of glutamine from skeletal muscle. We evaluated the hypothesis that the infusion of BCAA into undernourished rats would reduce the extent of mucosal atrophy and enhance the healing of anastomoses in the colon. Undernourished rats were randomized to receive 6 days of either a normal diet (Chow), conventional parenteral nutrition (CPN), or CPN supplemented with 1.8% BCAA (BCAA). The BCAA group had a higher plasma glutamine concentration than the Chow group (P less than 0.05). Compared with the CPN group, the BCAA group had the greater colonic mucosal weight (P less than 0.05) and colonic mucosal protein content (P less than 0.05), but there were no significant differences between groups in the bursting wall tension of the colon or the hydroxyproline content of the anastomoses. Although the infusion of BCAA has a beneficial effect on colonic atrophy, this did not result in the more secure healing of colonic anastomoses in this experimental model.
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PMID:The influence of branched chain amino acids on colonic atrophy and anastomotic strength in the rat. 189 89

It has been found that there exists a correlation in the dynamics of changes in the amount of glutamate, alpha-ketoglutarate, glutamine, ammonia and activity level or alpha-ketoglutarate dehydrogenase, NADP-glutamate dehydrogenase, glutamine synthetase and glutaminase in the brain of young carp in the process of winter starvation. It has been stated that under condition of energy deficiency and meaningful amount of ammonia in the organism of hibernating fish, its binding parallel with the known glutamine synthetase mechanism may proceed in the course of the NADP-glutamate dehydrogenase reaction which balance is shifted towards the glutamate synthesis. This reaction is supposed to provide the outflow of alpha-ketoglutarate from the citric cycle, which intensifies energy deficiency of the organism.
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PMID:[Features of the interconversion of alpha-ketoglutarate--glutamate in brain mitochondria of exothermic animals during hibernation]. 198 77


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