Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across dif...Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.展开更多
AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Para...AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.展开更多
Glutamine is the most abundant amino acid in milk, and lactation is associated with increased glutamine utilization both for milk synthesis and as a fuel for the enlarged small intestine. A number of recent studies ha...Glutamine is the most abundant amino acid in milk, and lactation is associated with increased glutamine utilization both for milk synthesis and as a fuel for the enlarged small intestine. A number of recent studies have indicated that lactation is accompanied by a mild catabolic state in which skeletal muscle proteins are degraded to provide amino acids that are used to synthesize additional glutamine. In this study we tested the hypothesis that supplemental L-glutamine or the commercially available glutamine supplement Aminogut （2.5% by weight mixed into daily feed） provided to gilts from 30 days prior to parturition until 21 days post-parturition would prevent a decrease in skeletal muscle glutamine while increasing the glutamine content of the milk. Muscle glutamine content decreased （P 〈 0.05） in control animals during lactation but this was prevented by supplementation with either L-glutamine or Aminogut. In this study, neither lactation nor supplementation had any effect on plasma glutamine or glutamate content. Free glutamine, and the total glutamine plus glutamate concentrations in milk from the control and the Aminogut group rose （P 〈 0.05） during the first 7 days of lactation, with milk concentrations in the L-glutamine supplemented group showing a similar trend （P = 0.053）. Milk glutamate remained constant between day 7 and 21 of lactation in the control and L-glutamine supplemented groups, but by day 21 of lactation the free glutamine, glutamate, and glutamine plus glutamate concentrations in milk from Aminogut-treated gilts were higher than those of control gilts. Thus dietary glutamine supplementation can alleviate the fall in intramuscular glutamine content during lactation in gilts, and may alleviate some of the catabolic effects of lactation. Furthermore, the increased milk glutamine content in the supplemented gilts may provide optimum nutrition for piglet development.展开更多
Root biomass of rice seedlings was increased at lower concentration of exogenous NH 4 + , but it was decreased at higher concentration of exogenous NH 4 + . The level of free NH 4 + in the roots was accumulated gradua...Root biomass of rice seedlings was increased at lower concentration of exogenous NH 4 + , but it was decreased at higher concentration of exogenous NH 4 + . The level of free NH 4 + in the roots was accumulated gradually with the increase of NH 4 + concentration in the nutrient solution. The content of the soluble proteins was essentially constant at higher NH 4 + . The activities of glutamine synthetase (GS), NADH-dependent glutamate synthase (NADH-GOGAT), and NADH-dependent glutamate dehydrogenase (NADH-GDH) were risen with exogenous NH 4 + concentration at the lower NH 4 + concentration range. But the activities of GS and NADH-GOGAT were declined, and the level of NADH-GDH activity was kept constant under higher NH 4 + concentration. The GS/GDH ratio suggested that NH 4 + was assimilated by GS-GOGAT cycle under lower NH 4 + concentration, but NADH-GDH was more important for NH 4 + assimilation and detoxifying NH 4 + to the tissue cells at the higher NH 4 + level. According to the growth and the activity changes of these ammonium-assimilating enzymes of rice seedling roots, 10. 0 μg/mL NH 4 + -N in nutrient solution was more suitable to the rice growth.展开更多
AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoper...AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoperated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, signif icantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modif ies the normal function in some brain regions.展开更多
Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major ch...Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major challenge.Interestingly,Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts.The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk,and observed that metabolic risk factors such as obesity,insulin resistance(IR),high blood pressure,and dyslipidemia were associated with several metabolites,including branched-chain amino acids,other hydrophobic amino acids,tryptophan breakdown products,and nucleotide metabolites.In addition,the authors found a significant association of IR traits with glutamine,glutamate and the glutamineto-glutamate ratio.These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk.We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions.We discuss here the critical role of the "liver metabolism" in the pathogenesis of the MS and IR,and postulate that before fatty liver develops,abnormal levels of liver enzymes,such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver.展开更多
BACKGROUND： Central sensitization, a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation, is an important mechanism underlying hyper...BACKGROUND： Central sensitization, a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation, is an important mechanism underlying hyperalgesia and neuropathic pain. Participation of the glutamate-glutamine cycle in central sensitization of the spinal cord remains poorly understood. OBJECTIVE： To determine whether the astrocyte-neuronal glutamate-glutamine cycle is involved in formalin-induced central sensitization in the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Orthopedics, Second Hospital, Lanzhou University, China from September 2007 to August 2008. MATERIALS： Methionine sulfoximine （MSO, 0.1 mmol/L）, glutamine （0.25 mmol/L）, and formalin were used for this study. METHODS： A total of 43 male, Sprague Dawley rats, aged 4 months, were randomly assigned to a sham operation group （n = 6） and a model group （n = 37）. Rats in the model group received intrathecal infusion in the spinal cord. 7 days later, 37 model rats were randomly divided into PBS, MSO, glutamine, MSO ＋ glutamine and formalin subcutaneous injection alone groups. The PBS, MSO, glutamine, MSO ＋ glutamine groups were respectively intrathecally injected with PBS, MSO, glutamine, MSO ＋ glutamine （50 μL each）, and then infused with 10 μL of saline. Rats from the sham operation group were not subjected to intrathecal infusion in the spinal cord. At 15 minutes after intrathecal injection, a rat model of formalin-induced inflammatory pain was established by subcutaneous injection of 5% formalin （50 μL） in the left hindpaw. MAIN OUTCOME MEASURES： Changes in spontaneous nociceptive behavior （licking/biting or flinching） were observed following formalin injection into the rat hindpaw. RESULTS： Compared with the PBS group, duration of licking/biting was significantly shortened, and flinching frequency was significantly diminished in the MSO group （P 〈 0.05）. Compared with the MSO group, duration of licking/biting was significantly prolonged, and flinching frequency was significantly increased in the MSO ＋ glutamine group （P 〈 0.05）. There was no significant difference in inflammatory pain behaviors among the sham operation, PBS, glutamine, MSO ＋ glutamine, and formalin subcutaneous injection alone groups （P 〉 0.05）. CONCLUSION： The astrocyte-neuronal glutamate-glutamine cycle in the spinal cord was shown to be involved in central sensitization induced by formalin subcutaneous injection into the hindpaw.展开更多
Tb(111) and Ca(11) ion equilibria in the presence of glutamic acid and glutamine were studied by potentiometric titration at 37'C and an ionic strength of 0. 15mol/L(NaCl) .The stability constants for Tb(111) and ...Tb(111) and Ca(11) ion equilibria in the presence of glutamic acid and glutamine were studied by potentiometric titration at 37'C and an ionic strength of 0. 15mol/L(NaCl) .The stability constants for Tb(111) and Ca(11)complexes in the systems were obtained. The species and their distribution in the systems were discussed.展开更多
Amino acids are very important compounds for the body and are involved in important functions that keep us healthy. Amino acids are essential components such as valine, proline, glutamine and glutamic acid. They can b...Amino acids are very important compounds for the body and are involved in important functions that keep us healthy. Amino acids are essential components such as valine, proline, glutamine and glutamic acid. They can be synthesized either naturally or artificially. To examine the metabolism and regulate the synthesis process, compounds labeled with nitrogen or carbon isotopes need to be used. These isotopic compounds allow for more extensive research and enable studies that would otherwise be impossible. However, their use is dependent on the availability of simple, efficient methods for isotopic analysis. Currently, the determination of the atomic fraction of carbon and nitrogen isotopes is only possible through their conversion into molecular nitrogen or carbon monoxide or carbon dioxide. This leads to the loss of information about isotopic enrichment in specific centers of the molecule. This article explores a new direct approach to determining the atomic fraction of carbon and nitrogen isotopes in the isotope-modified or identical centers of these compounds. This method eliminates the transfer process and dilution due to nitrogen and carbon impurities. It is now possible to simultaneously determine the atomic fraction of nitrogen and carbon isotopes in the research substance. This method can be applied to amino acids, making it an effective tool for proposing new research methods. Several articles [1] [2] [3] have proposed similar methods for organic compounds and amino acids.展开更多
Our previous behavioral studies have indicated that the astroglial glutamate-giutamine cycle is involved in the process of formalin-induced spinal cord central sensitization, but there was little morphological evidenc...Our previous behavioral studies have indicated that the astroglial glutamate-giutamine cycle is involved in the process of formalin-induced spinal cord central sensitization, but there was little morphological evidence. In this study, double-labeling immunofluorescence techniques showed that after rats were intrathecally injected with PBS and plantarly injected with formalin, glial fibrillary acidic protein （GFAP） and glutamine synthesase （GS） expression were increased and GFAP/GS coexpression was changed to include layers III and IV. After intrathecal injection of methionine sulfoximine, a GS specific inhibitor, the formalin-induced change in expression and coexpression of GFAP and GS in spinal cord dorsal horns was inhibited. The morphology, distribution and quantity of astrocytes recovered to normal levels. An intrathecal glutamine injection reversed the inhibitory effect of methionine sulfoximine. Astrocytes showed significant activation and distribution extended to layers V and VI. The present study provides morphological evidence that the astroglial glutamateglutamine cycle is involved in the process of formalin-induced spinal cord central sensitization.展开更多
[Objectives] This study was conducted to clarify the evolution characteristics of foxtail millet varieties in different ages and provide a basis for the breeding of new varieties. [Methods] A field experiment was carr...[Objectives] This study was conducted to clarify the evolution characteristics of foxtail millet varieties in different ages and provide a basis for the breeding of new varieties. [Methods] A field experiment was carried out on 20 main foxtail millet varieties promoted in North China developed from the 1980 s to 2000 s. The physiological and biochemical indexes of different foxtail millet varieties in four ages were compared, including chlorophyll content, soluble protein content, glutamine synthetase(GS) activity and glutamate synthase(GOGAT) activity, and the correlation between enzyme activity and yield was analyzed. [Results] The chlorophyll SPAD values of the flag leaf and functional leaves of foxtail millet varieties decreased with the filling process. The SPAD values of the flag leaf, top second leaf and top third leaf were higher in the varieties developed in the 1990 s and 2000 s than those in the 1980 s and 2010 s. The activity of glutamine synthetase(GS) and glutamate synthase(GOGAT) showed a single-peak curve in different foxtail millet varieties developed in the recent 30 years, and the peaks of the two were at 7 d and at 7 or 14 d, respectively. The activity of GS and GOGAT increased with the breeding age. In the period from 7 d after anthesis to the mature period, the decreases in the soluble protein content followed an order of 2010 s, 2000 s, 1990 s and 1980 s from small to large, indicating that the degradation rate of various enzyme sources and metabolic regulators in foxtail millet plants decreased during the improvement process. At 35 d after anthesis, the correlation coefficient between GS activity and yield was-0.247, that is, there was a negative correlation with yield. And there was a significant positive correlation between GOGAT activity and yield, and the correlation coefficient was as high as 0.455 at 7 d after anthesis. [Conclusions] Changes in the GS activity, GOGAT activity and soluble protein content in the flag leaf of foxtail millet varieties developed in recent years have a certain impact on yield.展开更多
Glutamine and glutamate are not considered essential amino acids but they play important roles in maintaining growth and health in both neonates and adults. Although glutamine and glutamate are highly abundant in most...Glutamine and glutamate are not considered essential amino acids but they play important roles in maintaining growth and health in both neonates and adults. Although glutamine and glutamate are highly abundant in most feedstuffs there is increasing evidence that they may be limiting during pregnancy, lactation and neonatal growth, particularly when relatively low protein diets are fed. Supplementation of diets with glutamine, glutamate or both at 0.5 to 1.0% to both suckling and recently weaned piglets improves intestinal and immune function and results in better growth. In addition such supplementation to the sow prevents some of the loss of lean body mass during lactation, and increases milk glutamine content. However, a number of important questions related to physiological condition,species under study and the form and amount of the supplements need to be addressed before the full benefits of glutamine and glutamate supplementation in domestic animal production can be realized.展开更多
Weaning stress may cause reduced energy intake for maintenance of mucosal structure.Gln,Glu,and Asp are major energy sources for the small intestine.This study investigated whether Gln,Glu,and Asp improve the intestin...Weaning stress may cause reduced energy intake for maintenance of mucosal structure.Gln,Glu,and Asp are major energy sources for the small intestine.This study investigated whether Gln,Glu,and Asp improve the intestinal morphology via regulating the energy metabolism in weaning piglets.A total of 198 weaned piglets were assigned to 3 treatments:Control(Basal diet+1.59%L-Ala);T1(Basal diet+1%L-Gln+0.5%L-Glu+0.1%L-Asp);T2(Low energy diet+1%L-Gln+0.5%L-Glu+0.1%L-Asp).Jejunum and ileum were obtained on d 5 or 21 post-weaning.T1 enhanced growth performance.T1 and T2 treatments improved small intestinal morphology by increasing villus height,goblet cell number and decreasing crypt depth.Days post-weaning affected the efficacy of T2,but not T1,on energy metabolism.At normal energy supplementation,Gln,Glu,and Asp restored small intestinal energy homeostasis via replenishing the Krebs'cycle and down-regulating the AMPK(adenosine monophosphate activated protein kinase)pathway.As these are not sufficient to maintain the intestinal energy-balance of piglets fed with a low energy diet on d 5 post-weaning,the AMPK,glycolysis,beta-oxidation,and mitochondrial biogenesis are activated to meet the high energy demand of enterocytes.These data indicated that Gln,Glu,and Asp could restore the energy homeostasis of intestinal mucosa of weaning piglets under normal energy fed.Low energy feeding may increase the susceptibility of piglets to stress,which may decrease the efficacy of Gln,Glu,and Asp on the restoration of energy balance.These findings provide new information on nutritional intervention for insufficient energy intake in weaning piglets.展开更多
A previous study has demonstrated that early weaning significantly suppressed hepatic glucose metabolism in piglets.Glutamate(Glu),aspartate(Asp)and glutamine(Gln)are major metabolic fuels for the small intestine and ...A previous study has demonstrated that early weaning significantly suppressed hepatic glucose metabolism in piglets.Glutamate(Glu),aspartate(Asp)and glutamine(Gln)are major metabolic fuels for the small intestine and can alleviate weaning stress,and therefore might improve hepatic energy metabolism.The objective of this study was to investigate the effects of administration of Glu,Asp and Gln on the expression of hepatic genes and proteins involved in lipid metabolism in post-weaning piglets.Thirty-six weaned piglets were assigned to the following treatments:control diet(Control;basal diet+15.90 g/kg alanine);Asp,Gln and Glu-supplemented diet(Control+AA;basal diet+1.00 g/kg Asp+5.00 g/kg Glu+10.00 g/kg Gln);and the energy-restricted diet supplemented with Asp,Gln and Glu(Energy^-+AA;energy deficient diet+1.00 g/kg Asp+5.00 g/kg Glu+10.00 g/kg Gln),Liver samples were obtained on d 5 and 21 post-weaning.Piglets fed Energy^-+AA diet had higher liver mRNA abundances of acyl-CoA oxidase 1(ACOX1),succinate dehydrogenase(SDH),mitochondrial transcription factor A(TFAM)and sirtuin 1(SIRT1),as well as higher protein expression of serine/threonine protein kinase 11(LKB1),phosphor-acetyl-CoA carboxylase(P-ACC)and SIRT1 compared with piglets fed control diet(P<0.05)on d 5 post-weaning.Control+AA diet increased liver malic enzyme 1(ME1)and SIRT1 mRNA levels,as well as protein expression of LKBl and P-ACC on d 5 post-weaning(P<0.05).On d 21 post-weaning,compared to control group,Glu,Gln and Asp supplementation up-regulated the mRNA levels of ACOX1,ME1 and SIRT1(P<0.05).These findings indicated that dietary Glu,Gln and Asp supplementation could improve hepatic lipid metabolism to some extent,which may provide nutritional intervention for the insufficient energy intake after weaning in piglets.展开更多
基金supported by Georgia Research Alliance and the National Natural Science Foundation of China(Grant Nos.81320108025,61402194,61572227)the Science-Technology Development Project from Jilin Province(Nos.20160101259JC,20160204022GX,20170520063JH)
文摘Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.
基金Supported by VU University Medical Center,Amsterdam,The Netherlands
文摘AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.
基金Ajinomoto do Brasil/FUNCAP-Fundaao Cearense de Apoio ao Desenvolvimento Científico/CNPq-Conselho Nacional de Desenvolvimento Científico e Tecnológico
文摘Glutamine is the most abundant amino acid in milk, and lactation is associated with increased glutamine utilization both for milk synthesis and as a fuel for the enlarged small intestine. A number of recent studies have indicated that lactation is accompanied by a mild catabolic state in which skeletal muscle proteins are degraded to provide amino acids that are used to synthesize additional glutamine. In this study we tested the hypothesis that supplemental L-glutamine or the commercially available glutamine supplement Aminogut （2.5% by weight mixed into daily feed） provided to gilts from 30 days prior to parturition until 21 days post-parturition would prevent a decrease in skeletal muscle glutamine while increasing the glutamine content of the milk. Muscle glutamine content decreased （P 〈 0.05） in control animals during lactation but this was prevented by supplementation with either L-glutamine or Aminogut. In this study, neither lactation nor supplementation had any effect on plasma glutamine or glutamate content. Free glutamine, and the total glutamine plus glutamate concentrations in milk from the control and the Aminogut group rose （P 〈 0.05） during the first 7 days of lactation, with milk concentrations in the L-glutamine supplemented group showing a similar trend （P = 0.053）. Milk glutamate remained constant between day 7 and 21 of lactation in the control and L-glutamine supplemented groups, but by day 21 of lactation the free glutamine, glutamate, and glutamine plus glutamate concentrations in milk from Aminogut-treated gilts were higher than those of control gilts. Thus dietary glutamine supplementation can alleviate the fall in intramuscular glutamine content during lactation in gilts, and may alleviate some of the catabolic effects of lactation. Furthermore, the increased milk glutamine content in the supplemented gilts may provide optimum nutrition for piglet development.
文摘Root biomass of rice seedlings was increased at lower concentration of exogenous NH 4 + , but it was decreased at higher concentration of exogenous NH 4 + . The level of free NH 4 + in the roots was accumulated gradually with the increase of NH 4 + concentration in the nutrient solution. The content of the soluble proteins was essentially constant at higher NH 4 + . The activities of glutamine synthetase (GS), NADH-dependent glutamate synthase (NADH-GOGAT), and NADH-dependent glutamate dehydrogenase (NADH-GDH) were risen with exogenous NH 4 + concentration at the lower NH 4 + concentration range. But the activities of GS and NADH-GOGAT were declined, and the level of NADH-GDH activity was kept constant under higher NH 4 + concentration. The GS/GDH ratio suggested that NH 4 + was assimilated by GS-GOGAT cycle under lower NH 4 + concentration, but NADH-GDH was more important for NH 4 + assimilation and detoxifying NH 4 + to the tissue cells at the higher NH 4 + level. According to the growth and the activity changes of these ammonium-assimilating enzymes of rice seedling roots, 10. 0 μg/mL NH 4 + -N in nutrient solution was more suitable to the rice growth.
基金Supported by Grant B013 from the University of Buenos Aires, Argentina and PIP 5869 from National Research Council of Argentina
文摘AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoperated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, signif icantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modif ies the normal function in some brain regions.
基金Supported by Grants PICT 2008-1521 and 2010-0441,from Agencia Nacional de Promoción Científica y TecnológicaUBACYT CM04,from Universidad de Buenos Aires
文摘Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major challenge.Interestingly,Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts.The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk,and observed that metabolic risk factors such as obesity,insulin resistance(IR),high blood pressure,and dyslipidemia were associated with several metabolites,including branched-chain amino acids,other hydrophobic amino acids,tryptophan breakdown products,and nucleotide metabolites.In addition,the authors found a significant association of IR traits with glutamine,glutamate and the glutamineto-glutamate ratio.These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk.We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions.We discuss here the critical role of the "liver metabolism" in the pathogenesis of the MS and IR,and postulate that before fatty liver develops,abnormal levels of liver enzymes,such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver.
基金the National Science Foundation of China,No.30800333
文摘BACKGROUND： Central sensitization, a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation, is an important mechanism underlying hyperalgesia and neuropathic pain. Participation of the glutamate-glutamine cycle in central sensitization of the spinal cord remains poorly understood. OBJECTIVE： To determine whether the astrocyte-neuronal glutamate-glutamine cycle is involved in formalin-induced central sensitization in the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Orthopedics, Second Hospital, Lanzhou University, China from September 2007 to August 2008. MATERIALS： Methionine sulfoximine （MSO, 0.1 mmol/L）, glutamine （0.25 mmol/L）, and formalin were used for this study. METHODS： A total of 43 male, Sprague Dawley rats, aged 4 months, were randomly assigned to a sham operation group （n = 6） and a model group （n = 37）. Rats in the model group received intrathecal infusion in the spinal cord. 7 days later, 37 model rats were randomly divided into PBS, MSO, glutamine, MSO ＋ glutamine and formalin subcutaneous injection alone groups. The PBS, MSO, glutamine, MSO ＋ glutamine groups were respectively intrathecally injected with PBS, MSO, glutamine, MSO ＋ glutamine （50 μL each）, and then infused with 10 μL of saline. Rats from the sham operation group were not subjected to intrathecal infusion in the spinal cord. At 15 minutes after intrathecal injection, a rat model of formalin-induced inflammatory pain was established by subcutaneous injection of 5% formalin （50 μL） in the left hindpaw. MAIN OUTCOME MEASURES： Changes in spontaneous nociceptive behavior （licking/biting or flinching） were observed following formalin injection into the rat hindpaw. RESULTS： Compared with the PBS group, duration of licking/biting was significantly shortened, and flinching frequency was significantly diminished in the MSO group （P 〈 0.05）. Compared with the MSO group, duration of licking/biting was significantly prolonged, and flinching frequency was significantly increased in the MSO ＋ glutamine group （P 〈 0.05）. There was no significant difference in inflammatory pain behaviors among the sham operation, PBS, glutamine, MSO ＋ glutamine, and formalin subcutaneous injection alone groups （P 〉 0.05）. CONCLUSION： The astrocyte-neuronal glutamate-glutamine cycle in the spinal cord was shown to be involved in central sensitization induced by formalin subcutaneous injection into the hindpaw.
文摘Tb(111) and Ca(11) ion equilibria in the presence of glutamic acid and glutamine were studied by potentiometric titration at 37'C and an ionic strength of 0. 15mol/L(NaCl) .The stability constants for Tb(111) and Ca(11)complexes in the systems were obtained. The species and their distribution in the systems were discussed.
文摘Amino acids are very important compounds for the body and are involved in important functions that keep us healthy. Amino acids are essential components such as valine, proline, glutamine and glutamic acid. They can be synthesized either naturally or artificially. To examine the metabolism and regulate the synthesis process, compounds labeled with nitrogen or carbon isotopes need to be used. These isotopic compounds allow for more extensive research and enable studies that would otherwise be impossible. However, their use is dependent on the availability of simple, efficient methods for isotopic analysis. Currently, the determination of the atomic fraction of carbon and nitrogen isotopes is only possible through their conversion into molecular nitrogen or carbon monoxide or carbon dioxide. This leads to the loss of information about isotopic enrichment in specific centers of the molecule. This article explores a new direct approach to determining the atomic fraction of carbon and nitrogen isotopes in the isotope-modified or identical centers of these compounds. This method eliminates the transfer process and dilution due to nitrogen and carbon impurities. It is now possible to simultaneously determine the atomic fraction of nitrogen and carbon isotopes in the research substance. This method can be applied to amino acids, making it an effective tool for proposing new research methods. Several articles [1] [2] [3] have proposed similar methods for organic compounds and amino acids.
基金the National Natural Science Foundation of China, No. 30800333the Fundamental Research Funds for the Central Universities, No. lzujbky-2010-148
文摘Our previous behavioral studies have indicated that the astroglial glutamate-giutamine cycle is involved in the process of formalin-induced spinal cord central sensitization, but there was little morphological evidence. In this study, double-labeling immunofluorescence techniques showed that after rats were intrathecally injected with PBS and plantarly injected with formalin, glial fibrillary acidic protein （GFAP） and glutamine synthesase （GS） expression were increased and GFAP/GS coexpression was changed to include layers III and IV. After intrathecal injection of methionine sulfoximine, a GS specific inhibitor, the formalin-induced change in expression and coexpression of GFAP and GS in spinal cord dorsal horns was inhibited. The morphology, distribution and quantity of astrocytes recovered to normal levels. An intrathecal glutamine injection reversed the inhibitory effect of methionine sulfoximine. Astrocytes showed significant activation and distribution extended to layers V and VI. The present study provides morphological evidence that the astroglial glutamateglutamine cycle is involved in the process of formalin-induced spinal cord central sensitization.
基金Supported by The Earmarked Fund for Modern Agro-industry Technology Research System(CARS-06-13.5-A19)Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences(GXGC2018D02)Shandong Key R&D Program(2018GNC113016)
文摘[Objectives] This study was conducted to clarify the evolution characteristics of foxtail millet varieties in different ages and provide a basis for the breeding of new varieties. [Methods] A field experiment was carried out on 20 main foxtail millet varieties promoted in North China developed from the 1980 s to 2000 s. The physiological and biochemical indexes of different foxtail millet varieties in four ages were compared, including chlorophyll content, soluble protein content, glutamine synthetase(GS) activity and glutamate synthase(GOGAT) activity, and the correlation between enzyme activity and yield was analyzed. [Results] The chlorophyll SPAD values of the flag leaf and functional leaves of foxtail millet varieties decreased with the filling process. The SPAD values of the flag leaf, top second leaf and top third leaf were higher in the varieties developed in the 1990 s and 2000 s than those in the 1980 s and 2010 s. The activity of glutamine synthetase(GS) and glutamate synthase(GOGAT) showed a single-peak curve in different foxtail millet varieties developed in the recent 30 years, and the peaks of the two were at 7 d and at 7 or 14 d, respectively. The activity of GS and GOGAT increased with the breeding age. In the period from 7 d after anthesis to the mature period, the decreases in the soluble protein content followed an order of 2010 s, 2000 s, 1990 s and 1980 s from small to large, indicating that the degradation rate of various enzyme sources and metabolic regulators in foxtail millet plants decreased during the improvement process. At 35 d after anthesis, the correlation coefficient between GS activity and yield was-0.247, that is, there was a negative correlation with yield. And there was a significant positive correlation between GOGAT activity and yield, and the correlation coefficient was as high as 0.455 at 7 d after anthesis. [Conclusions] Changes in the GS activity, GOGAT activity and soluble protein content in the flag leaf of foxtail millet varieties developed in recent years have a certain impact on yield.
文摘Glutamine and glutamate are not considered essential amino acids but they play important roles in maintaining growth and health in both neonates and adults. Although glutamine and glutamate are highly abundant in most feedstuffs there is increasing evidence that they may be limiting during pregnancy, lactation and neonatal growth, particularly when relatively low protein diets are fed. Supplementation of diets with glutamine, glutamate or both at 0.5 to 1.0% to both suckling and recently weaned piglets improves intestinal and immune function and results in better growth. In addition such supplementation to the sow prevents some of the loss of lean body mass during lactation, and increases milk glutamine content. However, a number of important questions related to physiological condition,species under study and the form and amount of the supplements need to be addressed before the full benefits of glutamine and glutamate supplementation in domestic animal production can be realized.
基金This project was supported by the National Natural Science Foundation of China(U20A2054,32072745)Innovation Province Project(2019RS3021)+1 种基金Postdoctoral Research Foundation of China(BX20180096)The authors thank Changsha Lvye Biotechnology Limited Company Academician Expert Workstation,Guangdong Wangda Group Academician Workstation for Clean Feed Technology Research and Development in Swine for providing technical assistance.
文摘Weaning stress may cause reduced energy intake for maintenance of mucosal structure.Gln,Glu,and Asp are major energy sources for the small intestine.This study investigated whether Gln,Glu,and Asp improve the intestinal morphology via regulating the energy metabolism in weaning piglets.A total of 198 weaned piglets were assigned to 3 treatments:Control(Basal diet+1.59%L-Ala);T1(Basal diet+1%L-Gln+0.5%L-Glu+0.1%L-Asp);T2(Low energy diet+1%L-Gln+0.5%L-Glu+0.1%L-Asp).Jejunum and ileum were obtained on d 5 or 21 post-weaning.T1 enhanced growth performance.T1 and T2 treatments improved small intestinal morphology by increasing villus height,goblet cell number and decreasing crypt depth.Days post-weaning affected the efficacy of T2,but not T1,on energy metabolism.At normal energy supplementation,Gln,Glu,and Asp restored small intestinal energy homeostasis via replenishing the Krebs'cycle and down-regulating the AMPK(adenosine monophosphate activated protein kinase)pathway.As these are not sufficient to maintain the intestinal energy-balance of piglets fed with a low energy diet on d 5 post-weaning,the AMPK,glycolysis,beta-oxidation,and mitochondrial biogenesis are activated to meet the high energy demand of enterocytes.These data indicated that Gln,Glu,and Asp could restore the energy homeostasis of intestinal mucosa of weaning piglets under normal energy fed.Low energy feeding may increase the susceptibility of piglets to stress,which may decrease the efficacy of Gln,Glu,and Asp on the restoration of energy balance.These findings provide new information on nutritional intervention for insufficient energy intake in weaning piglets.
基金funded by Key Programs of frontier scientific research of the Chinese Academy of Sciences(QYZDY-SSWSMC008)Youth Innovation Team Project of ISA,CAS(2017QNCXTD_TBE)+1 种基金National Natural Science Foundation of China(No 31672433,31501964,31560640)the Earmarked Fund for China Agriculture Research System(CARS-35)
文摘A previous study has demonstrated that early weaning significantly suppressed hepatic glucose metabolism in piglets.Glutamate(Glu),aspartate(Asp)and glutamine(Gln)are major metabolic fuels for the small intestine and can alleviate weaning stress,and therefore might improve hepatic energy metabolism.The objective of this study was to investigate the effects of administration of Glu,Asp and Gln on the expression of hepatic genes and proteins involved in lipid metabolism in post-weaning piglets.Thirty-six weaned piglets were assigned to the following treatments:control diet(Control;basal diet+15.90 g/kg alanine);Asp,Gln and Glu-supplemented diet(Control+AA;basal diet+1.00 g/kg Asp+5.00 g/kg Glu+10.00 g/kg Gln);and the energy-restricted diet supplemented with Asp,Gln and Glu(Energy^-+AA;energy deficient diet+1.00 g/kg Asp+5.00 g/kg Glu+10.00 g/kg Gln),Liver samples were obtained on d 5 and 21 post-weaning.Piglets fed Energy^-+AA diet had higher liver mRNA abundances of acyl-CoA oxidase 1(ACOX1),succinate dehydrogenase(SDH),mitochondrial transcription factor A(TFAM)and sirtuin 1(SIRT1),as well as higher protein expression of serine/threonine protein kinase 11(LKB1),phosphor-acetyl-CoA carboxylase(P-ACC)and SIRT1 compared with piglets fed control diet(P<0.05)on d 5 post-weaning.Control+AA diet increased liver malic enzyme 1(ME1)and SIRT1 mRNA levels,as well as protein expression of LKBl and P-ACC on d 5 post-weaning(P<0.05).On d 21 post-weaning,compared to control group,Glu,Gln and Asp supplementation up-regulated the mRNA levels of ACOX1,ME1 and SIRT1(P<0.05).These findings indicated that dietary Glu,Gln and Asp supplementation could improve hepatic lipid metabolism to some extent,which may provide nutritional intervention for the insufficient energy intake after weaning in piglets.
