Levels Of Glutamate Dehydrogenase Activity Research Articles

The activity of platelet enzymes and subpopulation composition of monocytes in schizophrenia

IntroductionThe studies on various groups of patients with schizophrenia revealed impairments in immune system, glutamatergic, and antioxidant systems contributing substantially in schizophrenia pathogenesis.Objectives To search for links between the activities of platelet enzymes involved in glutamate and glutathione metabolism and monocytes’ subpopulation compositions in patients with schizophrenia and to identify possible correlations of the biomarkers with clinical data. Research objectives: determination of subpopulation ratio of monocytes; measurement of the activity levels of glutamate dehydrogenase (GDH), phosphate-activated glutaminase (PAG), glutathione reductase (GR) and glutathione S-transferase (GST) in blood platelets; search for correlations between these parameters and the scores by psychometric scales.Methods The study included 36 women aged 16-45 years with acute schizophrenia hospitalized in the Mental Health Research Centre with their current condition assessed as depressive-delusional. The control group consisted of 17 women 18-45 years old without somatic or mental pathology. GDH, PAG, GR and GST activities were measured by spectrophotometric methods, and numbers of monocyte subpopulations - “classical”, “intermediate”, “non-classical” - by flow cytometry. The Hamilton Depression Rating Scale (HAMD-17) was used to assess depression severity. The data was processed using the Statistica 8.0 software.Results The detected changes in monocyte subpopulations’ composition towards the increase in the proportion of cells having a pro-inflammatory phenotype (CD14++CD16+ “intermediate”) indicated the activation of inflammatory reactions. Also, the activities of platelet enzymes of glutathione metabolism (GR and GST) were significantly decreased (p<0.05). Moreover, GDH and GST activities significantly correlated with the scores by HAMD-17 (r=0.40, p=0.022 and r=0.45, p=0.030, respectively). The results indicate the presence of pathological inflammatory process, the decrease in activities of glutathione antioxidant metabolism enzymes and a link to glutamate metabolism involvement (GDH) in the studied patient group.Conclusions The identified redistribution in the monocyte subpopulations’ composition and decrease in the activity of enzymes involved in glutamate metabolism and antioxidant system indicate the involvement of the immune, glutamate and antioxidant systems in the pathogenesis of schizophrenia and may reflect a functional interaction between these systems.Disclosure of InterestNone Declared

Evaluation of Platelet Glutamate Dehydrogenase Activity in Late-Life Depressions

The aim of the study is to evaluate the activity of platelet glutamate dehydrogenase (GDH) in late-life depression compared to the healthy control group and to reveal possible correlations with clinical data. Patients and methods: 42 elderly patients (60–86 years old) with depressive episodes of different nosological categories according to ICD-10 were examined: a single depressive episode (F32.0, F32.1), a depressive episode in recurrent depressive disorder (RDD — F33.0, F33.1) and a depressive episode in bipolar affective disorder (BD — F31.3). The activity of GDH and the severity of depression (using the Hamilton depressive scale, HAMD-17, and the Hamilton scale for assessing anxiety, HARS) were evaluated twice: before the starting the course of antidepressant therapy (day 0) and on the 28th day of the treatment course. Results: patients showed a significant decrease in the activity of GDH compared to the control group (p < 0.0008). Before the treatment, GDH activity was significantly reduced compared to the control in both RDD and BD (p < 0.002 and p < 0.004), whereas after the treatment, the decreased GDH activity was observed only in patients with BD (p < 0.002). When compared with the control group, male patients showed a significant decrease in GDH activity both before and after the treatment course (p < 0.017 and p < 0.027), whereas women patients showed the decrease only before the treatment (p < 0.014). Conclusion: the decreased platelet GDH activity in elderly depressions may indicate an impairment of glutamate metabolism. Gender differences were revealed in the reversal of GDH activity level after the therapy: in men, the level of GDH activity did not recover to control values after the treatment course. An elevation in the level of GDH to control values over a 28-day course of therapy occurred only in patients with RDD, but not in patients with BD.

Therapeutic potentiality of a new flavonoid against ketamine induced glutamatergic dysregulation in schizophrenia: In vivo and in silico approach

Glutamate and dopamine hypotheses are leading theories of the pathophysiology of schizophrenia. Multiple lines of evidence suggest that dopaminergic and glutamatergic dysfunction is an underlying mechanism in schizophrenia. Since currently available antipsychotic drugs have significant untoward side effects, identification of new neuroprotective compounds from the medicinal plants may prove beneficial in neurodegenerative disorders. In our previous investigation we have isolated, characterized and reported a novel bioactive compound viz. 3-(3, 4-dimethoxy phenyl)-1-(4-methoxy phenyl) prop-2-en-1-one from the Celastrus paniculatus (CP) is used for the current clinical intervention of schizophrenia disease. The present study is mainly aimed to evaluate the neuroprotective potential of the above bioactive compound against ketamine-induced schizophrenia with particular reference to glutamate metabolism using in vivo and in silico methods. The decrease in glutamine content and the activity levels of glutamate dehydrogenase, glutamine synthetase, and glutaminase in different regions of the rat brain suggests lowered oxidative deamination and lowered mobilization of glutamate towards glutamine formation during ketamine-induced schizophrenia. Pre-treatment with the plant compound reversed the alterations in glutamate metabolism and restored the normal glutamatergic neurotransmission akin to the reference drug, clozapine. In addition, the compound has shown strong interaction and exhibited the highest binding energies against selected NMDA receptors with the lowest inhibition constant than the reference drug. Recoveries of these parameters during anti-schizophrenic treatment suggest that administration of plant compound might offer neuroprotection by interrupting the pathological cascade of glutamatergic neurotransmission that occurs during schizophrenia.

Effects of Parathion Toxin on Glutamate Dehydrogenase Enzyme Activity and Diabetes Induction

Introduction: The main propose of this study was to determine the effect of parathion on activity of glutamate dehydrogenase (GDH) as a key enzyme in second phase secretion of insulin and to determine serum glucose levels in rats. Methods: To conduct the study, 35 rats were randomly divided into five groups (n=7). The serum glucose level of each group was measured and the total average was calculated with a glucometer. The experimental groups (groups 1,2,3,4) received 0.5, 1, 1.5, and 2 mg/kg of parathion pesticide via IP injection; whereas, the control group received no treatment. All rats were kept in similar condition. Serum glucose levels of rats were measured 24h after the final injection. Glutamate dehydrogenase (GDH) activity in rat’s pancreas was measured by GDH activity assay kit and using a spectrophotometer at 570nm. Result: The levels of glucose in treatment groups significantly increased compared with the control group (P<0.01). The levels of GDH activity in rats increased after receiving 1.5 and 2 mg/kg of parathion pesticides compared with the control group (P<0.01, p<0.05). Conclusion: Regarding the results, parathion affects the GDH enzyme in the pancreatic islets and leads to insufficient secretion of insulin. Although insulin was increased and increased the intermediates of Krebs cycle, the rate of insulin secretion was not so high to overcome the increase of glucose caused by parathion organophosphate

Molecular cloning of glutamate dehydrogenase genes of Nicotiana plumbaginifolia: structure analysis and regulation of their expression by physiological and stress conditions

Two Nicotiana plumbaginifolia gdh genes ( gdhA and gdhB) encoding for NADH dependent glutamate dehydrogenase (GDH) were isolated by PCR and I-PCR (inverse-PCR) and sequenced. The coding sequence is interrupted by eight introns that are located in the same positions in both genes. Computer analysis of the promoter regions of gdhA (650 nt) and gdhB (1800 nt) revealed several conserved motifs and, for gdhB, the presence of an I-Box element known to have light dependent regulatory functions in plants. The response of the gdh genes to carbohydrate deprivation and to ammonium feeding and to various stress conditions (salinity, temperature shifts and heavy metals) was examined in callus culture. The results clearly showed that the carbohydrate status of the cell is the main factor affecting gdh genes expression. Stress condition may depress or increase gdh transcript levels, but theses are not always correlated to the corresponding levels of GDH activity. Altogether these results point to the existence of multiple levels of regulation (transcriptional and post-transcriptional) of gdh genes.

Cadmium increases the activity levels of glutamate dehydrogenase and cysteine synthase in Chlamydomonas reinhardtii

The presence of 300 μM Cd 2+ in culture medium was found to be toxic to Chlamydomonas reinhardtii, reducing growth and productivity by about 48%. Approximately 30% of the total cadmium in the medium was accumulated by the alga resulting in 0.88% of the algal dried biomass. Elemental analysis indicated a cadmium-dependent decrease in the C (about 3.2%) and N content (about 7.1%) within C. reinhardtii, while the S content increased by approximately 7.5%. In parallel, Cd 2+ produced a significant activation of the aminating glutamate dehydrogenase (EC 1.4.1.2) activity and also NAD +- and NADP +-isocitrate dehydrogenase (EC 1.1.1.41 and 1.1.1.42, respectively) activities upon 24 h of the exposure to 150 μM of the metal. These data are consistent with the key role of the glutamate dehydrogenase/isocitrate dehydrogenase system to supply the glutamate required for the Cd 2+-induction of phytochelatin synthesis in the alga. Moreover, the presence of cadmium in the culture medium enhances the sulfate uptake rate and the components of the cysteine synthase complex within the cells such as the serine acetyltransferase (EC 2.3.1.30) and O-acetyl-L-serine (thiol)lyase (EC 4.2.99.8) activities.

Nucleotide sequence and regulation of expression of the Aspergillus nidulans gdhA gene encoding NADP dependent glutamate dehydrogenase

The nucleotide sequence of the Aspergillus nidulans gdhA gene encoding NADP linked glutamate dehydrogenase has been determined and Northern blot analysis used to study the regulation of expression of this gene. The gdhA gene is 1485 nucleotides long and, by comparison with the corresponding Neurospora crassa am gene, has two putative introns of 53 nucleotides and a protein encoding region of 1380 nucleotides that codes for an inferred protein of 49.63 kDa which shows regions of homology with glutamate dehydrogenase proteins from a range of organisms. mRNA analysis of wild-type mycelium grown under a variety of conditions shows that: (a) the highest levels are seen with glucose as the carbon source with inorganic nitrogen; and (b) no gdhA mRNA is detectable when cells are transferred to amino acids as sole carbon source, closely matching the observed glutamate dehydrogenase activity levels under identical conditions. The results presented strongly suggest that a good carbon source is a prerequisite for transcription, but the molecular mechanism responsible is unclear.

Expression of the Escherichia coli glutamate dehydrogenase gene in the cyanobacterium Synechococcus PCC6301 causes ammonium tolerance

The unicellular cyanobacterium Synechococcus PCC6301 lacks a hybridisable homologue of the strongly conserved gdhA gene of E. coli that encodes NADP-specific glutamate dehydrogenase. This is consistent with the failure to find this enzyme in extracts of the cyanobacterium. The E. coli gdhA gene was transferred to Synechococcus PCC6301 by transformation with an integrative vector. High levels of glutamate dehydrogenase activity, similar to those found in ammonium grown E. coli cells, were found in these transformants. These transformed cyanobacteria displayed an ammonium tolerant phenotype, consistent with the action of their acquired glutamate dehydrogenase activity as an ammonium detoxification mechanism. Minor differences in colony size and in growth at low light intensity were also observed.

Identification of the ammonium‐dependent isoenzyme of glutamate dehydrogenase as the form induced by senescence or darkness stress in the first leaf of wheat

The level of glutamate dehydrogenase activity increases nearly 3 fold in detached wheat (Triticum aestivum L. cv. Capitole) leaves during 72 h incubation with 15 mM ammonia. De novo synthesis of one of the glutamate dehydrogenase isoenzymes is shown to be correlated with the activity increase, by using an immunochemical approach. The identification of the ammonia inducible isoenzyme as the form previously reported induced by darkness stress or senescence (Laurière et al. 1981, Physiol. Plant. 52: 151‐155), provides new information on the possible physiological significance of the response to ammonia.

Changes in activity levels of glutamate dehydrogenase and two transaminases of maternal liver during reproduction and after administration of oestradiol and progesterone in Zoarces viviparus (L.)

The enzyme activity per unit liver wet weight, the specific activity and the total liver activity level of glutamate dehydrogenase (GDH) and two transaminases (GOT and GPT) were studied during vitellogenesis and pregnancy. A steady level of activity was observed during the short summer vitellogenesis and during early pregnancy. During mid‐term pregnancy in October the activity level significantly increased.Administration of 5 and 100 μg oestradiol increased serum vitellogenin, total liver protein and the liver somatic index during late pregnancy. Oestradiol decreased activity and specific activity of the enzymes. However, expressing activity as total hepatic enzyme activity units in fish of standard body weight oestradiol had no effect.

The measurement of glutamate dehydrogenase activity in Praunus flexuosus and its role in the regulation of ammonium excretion

Abstract 1. 1. A strong correlation (r2 = 0.916) was found between glutamate dehydrogenase (GDH) activity and ammonium excretion in Praunus flexuosus suggesting a key regulatory role for this enzyme. 2. 2. The high level of GDH activity found in this mysid was sufficient to account for all the ammonium excreted. 3. 3. Activator-inhibitor studies imply that GDH may regulate energy production and growth, in addition to ammonium excretion. 4. 4. The GDH assay presented here appears useful as a technique for quantifying zooplankton ammonium excretion impacts in the world oceans.

Ammonium assimilation in Rhizobium meliloti.

We have characterized a mutant of Rhizobium meliloti strain 2011 which cannot use ammonium as a nitrogen source. This mutant, RTm2620, was found to have significantly altered glutamate synthase activity. Both the mutant and the wild-type strains had glutamate dehydrogenase activity, which, although stimulated in the presence of glutamate and ammonium, was apparently insufficient to allow ammonium assimmilation. We conclude that the glutamine synthetase-glutamate synthase pathway may be the normal mode of ammonium assimilation by this strain in the free-living state. Independent revertants of Rm2620 were isolated and fell into two classes. Class I revertants regained partial glutamate synthase activity and had the same levels of glutamate dehydrogenase activity as Rm2620. Class II revertants retained the altered glutamate synthase activity but acquired a very high level of assimilatory glutamate dehydrogenase activity. Both classes were found to be altered in their symbiotic properties, although the original Rm2620 mutant was normal in this regard.

The Location of Nitrite Reductase and Other Enzymes Related to Amino Acid Biosynthesis in the Plastids of Root and Leaves

Density gradient separation of plastids from leaf and root tissue was carried out. The distribution in the gradients of the activity of the following enzymes was determined: nitrite reductase, glutamine synthetase, acetolactate synthetase, aspartate aminotransferase, catalase, cytochrome oxidase, and triosephosphate isomerase. The distribution of chlorophyll was followed in gradients from leaf tissue. The presence of plastids that have retained their stroma enzymes was denoted by a peak of triosephosphate isomerase activity. Coincidental with this peak were bands of nitrite reductase, acetolactate synthetase, glutamine synthetase, and aspartate aminotransferase activity. The results suggest that most, if not all, the nitrite reductase and acetolactate synthetase activity of the cell is in the plastids. The plastids were found to contain only part of the total glutamine synthetase, aspartate aminotransferase, and triosephosphate dehydrogenase activity in the cell. Some evidence was obtained for low levels of glutamate dehydrogenase activity in chloroplasts.

Development of glucose-6-phosphate, malate, and glutamate dehydrogenase activities in the ventral half of the chick spinal cord in the absence of extrinsic neuronal connections

Microsurgical operations were performed on the neural tube of chick embryos after 50–53 hr of incubation. As a result of the operation, the ventral half of the brachial spinal cord developed in the absence of extrinsic neuronal connections. The levels of activity of glucose-6-phosphate dehydrogenase, malate dehydrogenase, and glutamate dehydrogenase were measured in the ventral half of the brachial spinal cord of both experimental and control embryos 11–21 days of development. The experimental values for both glucose-6-phosphate and malate dehydrogenases were similar to those of control embryos. The level of glutamate dehydrogenase activity was significantly less in the experimental embryos of 19, 20, and 21 days of development. These findings, when considered in the light of other studies, suggest that the differentiation of malate and glucose-6-phosphate dehydrogenase activities is not regulated either by extrinsic neuronal connections, and hence the level of neuronal stimulation, or by the over-all level of motor activity. The reduced levels of glutamate dehydrogenase activity, however, may be a direct reflection of the operative deficit, a reduction in the number of synaptic terminals.