Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glutaminase catalyzes reaction of glutamate to GABA.

ABSTRACT: Here, for the first time, we report an NMR spectroscopy study of l-Glutamine (Gln) conversion by Glutaminase (Glnase), which shows that the reaction involves two distinct steps. In the first step, Glnase rapidly hydrolyzes Gln to Glutamate (Glu) (?16.87 ?mol of Gln/min/mg of Glnase) and in the second step, Glu generated in the first step is decarboxylated into gamma-amino butyric acid (GABA) with a much slower rate (?0.185 ?mol/min/mg). When Glnase was added to the sample containing l-Glu alone, it was also converted to GABA, at a similar rate as in the second step mentioned above. The rate of Glu decarboxylation into GABA by Glnase is about an order of magnitude lower than that by commonly known enzyme, Glutamate decarboxylase. Potential impact of these findings, on the mechanistic aspects of Gln-Glu shuttle in neuroscience and glutaminolysis in tumors, is discussed.

SUBMITTER: Nanga RP

PROVIDER: S-EPMC4097173 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Glutaminase catalyzes reaction of glutamate to GABA.

Nanga Ravi Prakash Reddy RP DeBrosse Catherine C Singh Anup A D'Aquilla Kevin K Hariharan Hari H Reddy Ravinder R

Biochemical and biophysical research communications 20140419 4

Here, for the first time, we report an NMR spectroscopy study of l-Glutamine (Gln) conversion by Glutaminase (Glnase), which shows that the reaction involves two distinct steps. In the first step, Glnase rapidly hydrolyzes Gln to Glutamate (Glu) (∼16.87 μmol of Gln/min/mg of Glnase) and in the second step, Glu generated in the first step is decarboxylated into gamma-amino butyric acid (GABA) with a much slower rate (∼0.185 μmol/min/mg). When Glnase was added to the sample containing l-Glu alone, ...[more]

PMID: 24755074

Similar Datasets

Distinct Signaling by Ventral Tegmental Area Glutamate, GABA, and Combinatorial Glutamate-GABA Neurons in Motivated Behavior.

Project description:Ventral tegmental area (VTA) neurons play roles in reward and aversion. We recently discovered that the VTA has neurons that co-transmit glutamate and GABA (glutamate-GABA co-transmitting neurons), transmit glutamate without GABA (glutamate-transmitting neurons), or transmit GABA without glutamate (GABA-transmitting neurons). However, the functions of these VTA cell types in motivated behavior are unclear. To identify the functions of these VTA cell types, we combine recombinase mouse lines with INTRSECT2.0 vectors to selectively target these neurons. We find that VTA cell types have unique signaling patterns for reward, aversion, and learned cues. Whereas VTA glutamate-transmitting neurons signal cues predicting reward, VTA GABA-transmitting neurons signal cues predicting the absence of reward, and glutamate-GABA co-transmitting neurons signal rewarding and aversive outcomes without signaling learned cues related to those outcomes. Thus, we demonstrate that genetically defined subclasses of VTA glutamate and GABA neurons signal different aspects of motivated behavior.

| S-EPMC7556367 | biostudies-literature

Upregulation of the Glutaminase II Pathway Contributes to Glutamate Production upon Glutaminase 1 Inhibition in Pancreatic Cancer.

Project description:The targeting of glutamine metabolism specifically via pharmacological inhibition of glutaminase 1 (GLS1) has been translated into clinical trials as a novel therapy for several cancers. The results, though encouraging, show room for improvement in terms of tumor reduction. In this study, the glutaminase II pathway is found to be upregulated for glutamate production upon GLS1 inhibition in pancreatic tumors. Moreover, genetic suppression of glutamine transaminase K (GTK), a key enzyme of the glutaminase II pathway, leads to the complete inhibition of pancreatic tumorigenesis in vivo unveiling GTK as a new metabolic target for cancer therapy. These results suggest that current trials using GLS1 inhibition as a therapeutic approach targeting glutamine metabolism in cancer should take into account the upregulation of other metabolic pathways that can lead to glutamate production; one such pathway is the glutaminase II pathway via GTK.

| S-EPMC6851409 | biostudies-literature

Reconstitution of GABA, Glycine and Glutamate Transporters.

Project description:In contrast to water soluble enzymes which can be purified and studied while in solution, studies of solute carrier (transporter) proteins require both that the protein of interest is situated in a phospholipid membrane and that this membrane forms a closed compartment. An additional challenge to the study of transporter proteins has been that the transport depends on the transmembrane electrochemical gradients. Baruch I. Kanner understood this early on and first developed techniques for studying plasma membrane vesicles. This advanced the field in that the experimenter could control the electrochemical gradients. Kanner, however, did not stop there, but started to solubilize the membranes so that the transporter proteins were taken out of their natural environment. In order to study them, Kanner then had to find a way to reconstitute them (reinsert them into phospholipid membranes). The scope of the present review is both to describe the reconstitution method in full detail as that has never been done, and also to reveal the scientific impact that this method has had. Kanner's later work is not reviewed here although that also deserves a review because it too has had a huge impact.

| S-EPMC8763731 | biostudies-literature

Supernova: A Deoxyribozyme that Catalyzes a Chemiluminescent Reaction.

Project description:Functional DNA molecules are useful components in nanotechnology and synthetic biology. To expand the toolkit of functional DNA parts, in this study we used artificial evolution to identify a glowing deoxyribozyme called Supernova. This deoxyribozyme transfers a phosphate from a 1,2-dioxetane substrate to its 5' hydroxyl group, which triggers a chemiluminescent reaction and a flash of blue light. An engineered version of Supernova is only catalytically active in the presence of an oligonucleotide complementary to its 3' end, demonstrating that light production can be coupled to ligand binding. We anticipate that Supernova will be useful in a wide variety of applications, including as a signaling component in allosterically regulated sensors and in logic gates of molecular computers.

| S-EPMC9298802 | biostudies-literature

Reduced cortical GABA and glutamate in high schizotypy.

Project description:RationaleAbnormal functioning of the inhibitory gamma-aminobutyric acid (GABA) and excitatory (glutamate) systems is proposed to play a role in the development of schizophrenia spectrum disorder. Although results are mixed, previous 1H-magnetic resonance spectroscopy (MRS) studies in schizophrenia and clinical high-risk samples report these metabolites are altered in comparison to healthy controls. Currently, however, there are few studies of these metabolites in schizotypy samples, a personality dimension associated with the experience of schizophrenia and psychosis-like symptoms.ObjectivesWe investigated if GABA and glutamate metabolite concentrations are altered in people with high schizotypy. We also explored the relationship between resilience to stress, GABA metabolite concentrations and schizotypy.MethodsWe used MRS to examine GABA and glutamate levels in the medial prefrontal cortex in people with low and high schizotypy traits as assessed with the Schizotypal Personality Questionnaire. Resilience to stress was assessed using the Connor-Davidson Resilience Scale.ResultsCompared to individuals with low schizotypy traits, high schizotypy individuals showed lower cortical prefrontal GABA (F (1,38) = 5.18, p = 0.03, η2 = 0.09) and glutamate metabolite levels (F (1, 49) = 6.25, p = 0.02, η2 = 0.02). Furthermore, participants with high GABA and high resilience levels were significantly more likely to be in the low schizotypy group than participants with low GABA and high resilience or high GABA and low resilience (95% CI 1.07-1.34, p < .001).ConclusionsThese findings demonstrate that subclinical schizotypal traits are associated with abnormal functioning of both inhibitory and excitatory systems and suggest that these transmitters are implicated in a personality trait believed to be on a continuum with psychosis.

| S-EPMC8373725 | biostudies-literature

Single rodent mesohabenular axons release glutamate and GABA.

Project description:The lateral habenula (LHb) is involved in reward, aversion, addiction and depression through descending interactions with several brain structures, including the ventral tegmental area (VTA). The VTA provides reciprocal inputs to LHb, but their actions are unclear. Here we show that the majority of rat and mouse VTA neurons innervating LHb coexpress markers for both glutamate signaling (vesicular glutamate transporter 2; VGluT2) and GABA signaling (glutamic acid decarboxylase; GAD, and vesicular GABA transporter; VGaT). A single axon from these mesohabenular neurons coexpresses VGluT2 protein and VGaT protein and, surprisingly, establishes symmetric and asymmetric synapses on LHb neurons. In LHb slices, light activation of mesohabenular fibers expressing channelrhodopsin2 driven by VGluT2 (Slc17a6) or VGaT (Slc32a1) promoters elicits release of both glutamate and GABA onto single LHb neurons. In vivo light activation of mesohabenular terminals inhibits or excites LHb neurons. Our findings reveal an unanticipated type of VTA neuron that cotransmits glutamate and GABA and provides the majority of mesohabenular inputs.

| S-EPMC4843828 | biostudies-literature

FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders

Project description:Autism spectrum disorder (ASD) is a disorder of brain development believed, in most cases, to be of genetic origin. We use induced pluripotent stem cells (iPSCs)-derived 3-dimensional neural cultures (organoids) in patients with ASD and macrocephaly to investigate neurodevelopmental alterations that cause this form of ASD. By using transcriptome analyses, we identified modules of co-expressed genes significantly upregulated in ASD patients compared to non-ASD first-degree family members.

2015-07-16 | GSE61476 | GEO

Two-color, two-photon uncaging of glutamate and GABA.

Project description:We developed a caged GABA (gamma-aminobutyric acid), which, when combined with an appropriate caged glutamate, allows bimodal control of neuronal membrane potential with subcellular resolution using optically independent two-photon uncaging of each neurotransmitter. We used two-color, two-photon uncaging to fire and block action potentials from rat hippocampal CA1 neurons in brain slices with 720-nm and 830-nm light, respectively. Our method should be generalizable to other chemical messenger pairs.

| S-EPMC4135702 | biostudies-literature

New GABA/glutamate receptor target for [³H]isoxazoline insecticide.

Project description:The highly effective and selective isoxazoline insecticide A1443 is known to potently displace [(3)H]ethynylbicycloorthobenzoate ([(3)H]EBOB) binding to house fly head membranes with an IC50 of 0.2 nM in a manner characteristic of GABA-gated chloride channel antagonists. To further define its mode of action, we prepared phenyl-labeled [(3)H]A1443 as described with a specific activity of 14 Ci/mmol. This new radioligand with an apparent IC50 of about 0.4 nM is poorly displaced by most insecticides acting at the [(3)H]EBOB site. Interestingly, the isoxazoline binding site is directly coupled to the avermectin GABA/glutamate chloride channel activator site. These findings revive interest in the insect GABA/glutamate receptor as an insecticide target.

| S-EPMC3731417 | biostudies-literature

Prefrontal GABA and glutamate-glutamine levels affect sustained attention.

Project description:Attention levels fluctuate during the course of daily activities. However, factors underlying sustained attention are still unknown. We investigated mechanisms of sustained attention using psychological, neuroimaging, and neurochemical approaches. Participants were scanned with functional magnetic resonance imaging (fMRI) while performing gradual-onset, continuous performance tasks (gradCPTs). In gradCPTs, narrations or visual scenes gradually changed from one to the next. Participants pressed a button for frequent Go trials as quickly as possible and withheld responses to infrequent No-go trials. Performance was better for the visual gradCPT than for the auditory gradCPT, but the 2 were correlated. The dorsal attention network was activated during intermittent responses, regardless of sensory modality. Reaction-time variability of gradCPTs was correlated with signal changes (SCs) in the left fronto-parietal regions. We also used magnetic resonance spectroscopy (MRS) to measure levels of glutamate-glutamine (Glx) and γ-aminobutyric acid (GABA) in the left prefrontal cortex (PFC). Glx levels were associated with performance under undemanding situations, whereas GABA levels were related to performance under demanding situations. Combined fMRI-MRS results demonstrated that SCs of the left PFC were positively correlated with neurometabolite levels. These findings suggest that a neural balance between excitation and inhibition is involved in attentional fluctuations and brain dynamics.

| S-EPMC10545440 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data