Affinage

GLUD1

Glutamate dehydrogenase 1, mitochondrial · UniProt P00367

Length
558 aa
Mass
61.4 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GLUD1 encodes the mitochondrial glutamate dehydrogenase (hGDH1) that catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate (α-KG), feeding glutamate carbon into the TCA cycle for anaplerosis and energy production (PMID:11032875, PMID:22924626). The enzyme maintains substantial basal activity and is tightly governed by allosteric effectors—potently inhibited by GTP and activated by L-leucine and ADP—with the regulatory 'antenna' residue Arg-443 being essential for both catalytic and allosteric function (PMID:11032875, PMID:12324473). Loss of allosteric control is pathogenic: gain-of-function mutations that impair GTP inhibition (e.g., Y266C, P436L, G446V) drive unregulated glutamate oxidation and glutamine-stimulated insulin secretion, causing hyperinsulinism-hyperammonemia syndrome (PMID:11872671, PMID:19690084, PMID:32143698). The protein localizes principally to mitochondria, with a minor ER-associated pool, directed by an N-terminal mitochondrial signal sequence (PMID:19448744). In the nervous system GLUD1 supports glutamate synthesis/release at nerve terminals and is required for astrocytic oxidative catabolism of glutamate for Krebs cycle entry (PMID:19890003, PMID:22924626), while in muscle stem cells it acts as a metabolic brake on differentiation by preventing mitochondrial glutamate accumulation and malate-aspartate shuttle inhibition (PMID:39121856). GLUD1 abundance and localization are extensively controlled post-translationally: it translocates to the cytoplasm under amino-acid or glucose deprivation, where it is ubiquitinated and degraded by RNF213, with degradation lowering α-KG, reducing α-KG-dependent histone demethylase activity, and reprogramming gene expression to conserve nutrients (PMID:34269483). Additional E3 ligases (STUB1 at K503; the LASP1/SYVN1 axis) target GLUD1 for proteasomal degradation, whereas PRMT7-mediated arginine methylation at R76 (downstream of AKT1) and K84 deacetylation stabilize and activate the enzyme (PMID:37416474, PMID:38587834, PMID:39144257, PMID:41876450). In cancer, GLUD1 is transcriptionally induced via EGFR-MEK-ERK-ELK1 and phosphorylated by EGFR at Y135 to activate CaMKIV-CREB signaling, and it promotes anoikis resistance both enzymatically—through α-KG-driven CaMKK2-AMPK activation in LKB1-deficient cells—and non-enzymatically, by stabilizing ARAF to sustain MEK/ERK signaling (PMID:29249655, PMID:32034306, PMID:36516759, PMID:41786885).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Established that the GLUD1-encoded enzyme is a distinct allosterically regulated GDH isoform, defining its baseline catalytic and regulatory parameters.

    Evidence In vitro kinetic and allosteric assays with purified recombinant hGDH1 expressed in Sf9 cells

    PMID:11032875

    Open questions at the time
    • Does not address in vivo regulation or physiological effector concentrations
    • Allosteric structural basis not resolved
  2. 2002 High

    Identified Arg-443 in the antenna domain as essential for basal activity and L-leucine activation, linking a single residue to intersubunit communication and allosteric control.

    Evidence Site-directed mutagenesis (R443S) with recombinant expression and in vitro enzymatic assays

    PMID:12324473

    Open questions at the time
    • No structural model of the conformational change
    • Physiological consequence of antenna-domain regulation in cells untested here
  3. 2002 High

    Connected loss of GDH allosteric regulation to disease by showing a gain-of-function mutation drives glutamine-stimulated insulin secretion.

    Evidence Y266C mutagenesis, activity assays in COS-7, overexpression and insulin secretion assays in MIN6 insulinoma cells

    PMID:11872671

    Open questions at the time
    • Does not establish in vivo β-cell phenotype
    • Ammonemia mechanism not directly addressed
  4. 2009 High

    Defined GLUD1 subcellular distribution, establishing a dominant mitochondrial pool and a minor ER-associated full-length form dependent on the signal sequence.

    Evidence EGFP fusions in multiple cell lines, confocal microscopy, fractionation, signal-sequence deletion

    PMID:19448744

    Open questions at the time
    • Functional role of the ER-associated form unknown
    • No evidence yet for regulated cytoplasmic translocation
  5. 2009 High

    Demonstrated in vivo neuronal roles for GLUD1 in depolarization-induced glutamate release and synaptic transmission.

    Evidence Neuron-specific Glud1 transgenic overexpression, in vivo glutamate microelectrode measurements, mEPSC electrophysiology

    PMID:19890003

    Open questions at the time
    • Overexpression model may not reflect endogenous levels
    • Mechanism of release coupling not resolved
  6. 2012 High

    Established the requirement of GLUD1 for astrocytic oxidative glutamate catabolism and Krebs cycle entry in the brain in vivo.

    Evidence CNS-conditional Glud1 knockout (Nestin-Cre), NMR spectroscopy, enzymatic assays, electrophysiology, IHC

    PMID:22924626

    Open questions at the time
    • Compensatory transporter/glutamine synthetase upregulation complicates interpretation
    • No synaptic defect under standard conditions
  7. 2009 Medium

    Expanded the spectrum of GTP-insensitive activating mutations causing hyperinsulinism-hyperammonemia syndrome.

    Evidence GLUD1 sequencing and functional analysis of mutant GDH (P436L, N410D, D451V) in patient samples

    PMID:19690084

    Open questions at the time
    • Single-center cohort
    • Functional analysis limited to subset of mutations
  8. 2020 High

    Linked GLUD1 to oncogenic transcription and a structural basis for impaired GTP regulation in disease.

    Evidence ChIP and ELK1-Ser383 mutagenesis showing EGFR-MEK-ERK-ELK1 induction of GDH1; computational and patient-cell analysis of the G446V activating mutation

    PMID:32034306 PMID:32143698

    Open questions at the time
    • G446V functional data from single study in patient-derived cells
    • Transcriptional control mapped in glioblastoma only
  9. 2017 High

    Defined an enzymatic, α-KG-dependent mechanism by which GLUD1 confers anoikis resistance in LKB1-deficient cancer.

    Evidence Detachment assays, knockdown/overexpression, Co-IP of CamKK2-AMPK, metabolite measurement, patient-derived xenografts

    PMID:29249655

    Open questions at the time
    • Dependence on LKB1 status limits generality
    • PLAG1 induction mechanism not fully resolved
  10. 2021 High

    Revealed stress-induced cytoplasmic translocation and RNF213-mediated degradation of GLUD1 as a nutrient-conservation program coupling α-KG to epigenetic gene control.

    Evidence Fractionation, ubiquitination assays, RNF213 identification, α-KG metabolomics, histone-methylation ChIP

    PMID:34269483

    Open questions at the time
    • Trigger for mitochondria-to-cytosol relocation not fully defined
    • Reversibility of degradation upon refeeding untested
  11. 2022 Medium

    Identified EGFR phosphorylation of GLUD1 at Y135 as an activating modification driving CaMKIV-CREB pro-metastatic signaling.

    Evidence Phosphorylation and kinase assays, Co-IP, invasion/anoikis assays, patient tumor correlation

    PMID:36516759

    Open questions at the time
    • Single-lab biochemistry
    • Direct structural consequence of Y135 phosphorylation not shown
  12. 2023 Medium

    Mapped a second degradation route, identifying STUB1 as an E3 ligase and K503 as the primary GLUD1 ubiquitination site controlling tumor growth.

    Evidence Co-IP, ubiquitination assays, K503 mutagenesis, proliferation and xenograft assays

    PMID:37416474

    Open questions at the time
    • Single-lab, two orthogonal methods
    • Relationship to RNF213 pathway unresolved
  13. 2024 High

    Placed GLUD1 as a metabolic brake on muscle stem cell differentiation acting through mitochondrial glutamate and the malate-aspartate shuttle.

    Evidence Conditional Glud1 knockout in MuSCs, metabolomics, MAS rescue, NAD+/NADH manipulation, in vitro and in vivo differentiation assays

    PMID:39121856

    Open questions at the time
    • Compartment-specific NAD+/NADH measurement is inferential
    • Generalizability to other stem cell types unknown
  14. 2024 Medium

    Extended GLUD1 stability control to additional ligase axes and identified acetylation-coupled cytoplasmic functions and an AKT-suppressive role.

    Evidence Co-IP and ubiquitination assays defining LASP1/SYVN1-mediated degradation and GLUD1-AKT interaction; K84 acetylation mapping with TRIM21, KGA, and p62 interactions under glucose starvation

    PMID:38587834 PMID:39144257

    Open questions at the time
    • Single-lab Co-IP datasets
    • Functional integration of multiple competing ligases unclear
    • K63-ubiquitination role mechanistically incomplete
  15. 2026 Medium

    Established a non-enzymatic scaffolding function of GLUD1 (ARAF stabilization) and a stabilizing methylation modification (PRMT7/R76 downstream of AKT1).

    Evidence Co-IP and ubiquitination assays for GLUD1-ARAF stabilization with in vivo dissemination model; PRMT7 R76 methylation mapping with AKT1-T73 phosphorylation and xenografts

    PMID:41786885 PMID:41876450

    Open questions at the time
    • Single-lab biochemistry for each axis
    • Structural basis of ARAF binding and R76 methylation not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple competing post-translational modifications, ligases, and the enzymatic versus non-enzymatic activities of GLUD1 are integrated in a single cell to set its abundance, localization, and signaling output remains unresolved.
  • No unified model reconciling RNF213, STUB1, SYVN1, and TRIM21 ubiquitination
  • Relative contribution of enzymatic α-KG output versus scaffolding functions in tumors unquantified
  • Structural basis of mitochondria-to-cytoplasm translocation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0098772 molecular function regulator activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-112316 Neuronal System 2
Partners
AKT1ARAFEGFRLASP1PRMT7RNF213STUB1SYVN1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Human GLUD1-encoded GDH (hGDH1) displays distinct allosteric regulation compared to the nerve-specific GLUD2 isoform: hGDH1 maintains substantial basal activity (~35-40% of maximal) and is markedly inhibited by GTP (IC50 ~0.20 µM), whereas activation by L-leucine alone (~75%) requires higher concentrations without ADP. ADP synergizes with L-leucine to activate the enzyme. These properties differ from the GLUD2 enzyme, and distinct Km values for glutamate and α-ketoglutarate were determined for each isoform. Recombinant enzyme expression in Sf9 cells, in vitro kinetic and allosteric assays with purified hGDH1 and hGDH2 Journal of neurochemistry High 11032875
2002 Substitution of Ser for Arg-443 in the regulatory 'antenna' domain of GLUD1 GDH virtually abolishes basal enzymatic activity and abrogates L-leucine activation in the absence of ADP. With ADP present, L-leucine can activate the R443S mutant >2000%. The Arg-443 residue lies in a helix that undergoes conformational changes during catalysis and is involved in intersubunit communication; this single substitution is sufficient to impair both catalytic and allosteric function. Site-directed mutagenesis of GLUD1, recombinant expression, in vitro enzymatic assays The Journal of biological chemistry High 12324473
2002 A gain-of-function mutation Y266C in GLUD1 results in constitutively elevated GDH activity with severely impaired allosteric regulation by ADP and GTP. Overexpression of this mutant GDH (GDH266C) in insulinoma MIN6 cells causes glutamine-stimulated insulin secretion, demonstrating that unregulated GDH activity enhances oxidation of glutamate to α-ketoglutarate and thereby stimulates insulin secretion from pancreatic β-cells. Site-directed mutagenesis, COS-7 cell expression for activity assays, overexpression in MIN6 insulinoma cells, insulin secretion assays Diabetes High 11872671
2009 Human GLUD1 and GLUD2 GDH proteins localize primarily to mitochondria and, to a lesser extent, to the endoplasmic reticulum. Deletion of the mitochondrial signal sequence prevents mitochondrial entry and eliminates the ER-associated full-length form. Two molecular weight forms correspond to the mitochondrial (cleaved, ~90 kDa) and ER-associated (full-length, ~95 kDa) proteins. EGFP fusion constructs expressed in multiple cell lines (COS7, HeLa, CHO, HEK293, SHSY-5Y), confocal microscopy with organelle markers, Western blot fractionation, signal sequence deletion Biochemistry and cell biology High 19448744
2009 Transgenic (Tg) mice overexpressing Glud1 under the neuron-specific enolase promoter show increased GLUD protein activity in CNS neurons, increased in vivo depolarization-induced glutamate release in striatum, and increased frequency and amplitude of miniature EPSCs in CA1 hippocampus. This demonstrates that GLUD1 functions in the pathway of glutamate synthesis/release in nerve terminals. Transgenic mouse overexpression, in vivo glutamate microelectrode measurements, electrophysiological recordings (mEPSCs), immunohistochemistry The Journal of neuroscience High 19890003
2009 Activating mutations in GLUD1 (e.g., P436L, N410D, D451V) that impair GTP inhibition of GDH cause hyperinsulinism-hyperammonemia syndrome. Functional analysis confirmed that the P436L mutation abolishes GTP inhibitory regulation of the enzyme. GLUD1 gene sequencing, functional analysis of mutant GDH in patient samples European journal of endocrinology Medium 19690084
2012 CNS-specific deletion of Glud1 in mice causes deficient oxidative catabolism of glutamate in astrocytes (reduced astrocytic glutamate breakdown, requiring GDH for Krebs cycle entry). Brain glutamate levels remain unchanged while glutamine levels increase. Glutamate and glutamine transporters and glutamine synthetase are upregulated. Synaptic transmission is not altered under standard conditions. CNS-conditional Glud1 knockout mice (Nestin-Cre/LoxP), enzymatic activity assays, NMR spectroscopy, immunohistochemistry, electrophysiology Journal of neurochemistry High 22924626
2012 GLUD1 GDH properties differ from GLUD2: hGDH1 maintains substantial basal activity and is subject to potent GTP inhibition, while hGDH2 (with the Arg443Ser evolutionary change) has low basal activity, is insensitive to GTP at physiological concentrations, and is more responsive to activation by rising ADP/L-leucine levels. These properties were confirmed using purified recombinant proteins from Sf21 cell expression. Recombinant expression in Sf21 cells, in vitro enzymatic assays, allosteric regulation studies Neurochemistry international High 22658952
2017 GDH1 (GLUD1) promotes anoikis resistance and tumor metastasis in LKB1-deficient lung cancer. Upon detachment, GDH1 is upregulated via PLAG1 transcription factor. The GDH1 product α-ketoglutarate (α-KG) activates CamKK2 by enhancing its binding to substrate AMPK, thereby contributing to energy production that confers anoikis resistance. This GDH1-CamKK2-AMPK axis is particularly important in LKB1-deficient tumors where AMPK activation depends predominantly on CamKK2. Cell detachment assays, gene knockdown/overexpression, Co-IP (CamKK2-AMPK interaction), metabolite measurement, patient-derived xenograft model, correlation studies Molecular cell High 29249655
2020 EGFR activation upregulates GDH1 transcription through the MEK/ERK/ELK1 pathway in glioblastoma. EGFR triggers phosphorylation of ELK1 at Ser383 via MEK/ERK; phosphorylated ELK1 binds the GDH1 promoter to activate transcription. ELK1 knockdown or ELK1-Ser383 mutation prevents EGFR-induced GDH1 upregulation and glutamine metabolism activation. ChIP assay (ELK1 at GDH1 promoter), ELK1 knockdown, ELK1 Ser383 point mutation, Western blot for phosphorylation, luciferase reporter or direct measurement of GDH1 transcription Oncogene High 32034306
2020 A gain-of-function GLUD1 mutation G446V reduces the energy barrier between open and closed enzyme states, impairing allosteric inhibition by GTP and activation by ADP. Patient-derived lymphoblastoid cells carrying GDH-G446V show higher mitochondrial respiration in response to GDH-dependent substrates, indicating a metabolic shift toward glutaminolysis. Computational conformational energy analysis, enzymatic activity assay in patient-derived lymphoblastoid cells, mitochondrial respiration assay Human genomics Medium 32143698
2021 Under amino acid deprivation or mTORC1 inhibition, GDH1 translocates from mitochondria to the cytoplasm, where it is ubiquitinated and degraded via the E3 ligase RNF213. GDH1 degradation reduces intracellular α-KG levels and decreases activity of α-KG-dependent lysine demethylases (KDMs), leading to increased histone H3K9 and H3K27 methylation that suppresses ribosomal protein gene expression to preserve nutrients for cell survival. Cell fractionation, ubiquitination assays, E3 ligase identification (RNF213), metabolite measurement (α-KG), ChIP for histone methylation marks, gene expression analysis The EMBO journal High 34269483
2022 EGFR phosphorylates GDH1 at tyrosine 135, activating it. Activated GDH1 cooperates with RSK2 to enhance CREB activity via CaMKIV signaling, promoting metastasis. GDH1, RSK2, and CREB phosphorylation positively correlate with EGFR mutation/activation in lung cancer patient tumors. Phosphorylation assays, co-immunoprecipitation, kinase assays, cell invasion/anoikis resistance assays, patient tumor correlation Cell reports Medium 36516759
2023 STUB1 (CHIP) is the E3 ubiquitin ligase responsible for ubiquitin-mediated proteasomal degradation of GLUD1. Lysine 503 (K503) is the primary ubiquitination site on GLUD1. Inhibiting ubiquitination at K503 promotes proliferation and tumor growth of lung adenocarcinoma cells. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K503), cell proliferation and xenograft assays iScience Medium 37416474
2024 GLUD1 deletion in proliferating muscle stem cells (MuSCs) causes mitochondrial glutamate accumulation and inhibition of the malate-aspartate shuttle (MAS), leading to compartment-specific NAD+/NADH ratio shifts. This triggers precocious differentiation and fusion, and loss of self-renewal in vitro and in vivo. Restoring MAS activity or directly altering NAD+/NADH ratios normalizes myogenesis, placing GLUD1 as a metabolic brake on MuSC differentiation acting through mitochondrial glutamate levels and the MAS. Conditional Glud1 knockout in MuSCs, metabolomics (mitochondrial glutamate/α-KG), MAS activity rescue, NAD+/NADH manipulation, in vitro and in vivo differentiation assays Developmental cell High 39121856
2024 LASP1 interacts with GLUD1 and promotes its degradation via the ubiquitin-proteasome pathway, relying on the E3 ubiquitin ligase SYVN1 (synoviolin). LASP1 enhances SYVN1-GLUD1 interaction to facilitate GLUD1 ubiquitination. In HBV-related HCC, HBX protein suppresses GLUD1 through this LASP1/SYVN1 axis. GLUD1 interacts with AKT and α-KG produced by GLUD1 suppresses AKT activation. Co-immunoprecipitation, ubiquitination assays, gene silencing, Western blot Journal of molecular cell biology Medium 38587834
2024 Glucose starvation reduces GLUD1 acetylation at Lys84, which promotes active hexamer formation and GLUD1 enzymatic activity. Under glucose starvation, deacetylated GLUD1 translocates to the cytoplasm where it is ubiquitinated in K63-linkage by TRIM21 and binds cytoplasmic glutaminase KGA, enhancing glutamine metabolism. Cytoplasmic GLUD1 also interacts with p62, preventing p62 acetylation and blocking autophagic cell death in lung adenocarcinoma cells. Acetylation site mapping, Co-immunoprecipitation (GLUD1-KGA, GLUD1-p62), ubiquitination assays, cell fractionation, glucose starvation experiments Cell insight Medium 39144257
2026 GLUD1 interacts with ARAF proto-oncogene protein and limits its ubiquitin-proteasome-mediated degradation, thereby stabilizing ARAF protein levels and sustaining MEK/ERK signaling. This represents a non-enzymatic function of GLUD1 that supports anoikis resistance during peritoneal dissemination of ovarian cancer. Co-immunoprecipitation (GLUD1-ARAF interaction), ubiquitination assays, GLUD1 knockdown/overexpression, in vitro anoikis assays, in vivo peritoneal dissemination model NPJ precision oncology Medium 41786885
2026 PRMT7 mediates monomethylation of GLUD1 at arginine 76 (R76), which enhances GLUD1 protein stability by antagonizing ubiquitin-dependent proteasomal degradation. AKT1 phosphorylates PRMT7 at threonine 73 (T73) to promote PRMT7 activity toward GLUD1, stabilizing GLUD1 and supporting glutamine metabolism in gastric cancer cells. Co-immunoprecipitation, site-directed mutagenesis (R76, T73), ubiquitination assays, kinase assays, xenograft models Cell death & disease Medium 41876450
2015 Manganese (Mn) inhibits hGDH1 (GLUD1-encoded) enzymatic activity in vitro with an IC50 of ~1.54 mM at 0.25 mM ADP, exhibiting sigmoidal inhibition kinetics. This is a less potent and less cooperative inhibition compared to hGDH2, suggesting differential sensitivity of the two isoforms to Mn at physiologically relevant ADP levels. In vitro enzymatic inhibition assay with purified recombinant hGDH1 and hGDH2, determination of IC50 and Hill coefficients Neurochemistry international Medium 25837286
2024 PARP14 inhibits GLUD1 enzymatic activity via mono-ADP-ribosylation (MARylation), reducing α-KG production and suppressing energy metabolism. ECH (echinacoside) downregulates PARP14 expression, reversing this inhibition and restoring GLUD1-dependent glutamine metabolism and mitochondrial function in ovarian granulosa cells. Co-immunoprecipitation, enzymatic activity assay, siRNA knockdown, metabolomics, mitochondrial functional assays Phytomedicine Low 41895093
2025 Nuclear PHGDH regulates GLUD1 transcription via interaction with the transcription factor STAT3. ChIP-qPCR and co-immunoprecipitation showed nuclear PHGDH interacts with STAT3 to repress GLUD1 (and GLS2) gene expression, affecting macrophage polarization. STAT3 inhibition reversed the effects of PHGDH on macrophage function. ChIP-qPCR, co-immunoprecipitation, gene silencing, rescue experiments Cancer biology & medicine Medium 40434360
2025 SIRT3-dependent deacetylation of GLUD1 is promoted by the SENP1-Sirt3 signaling pathway activated by A-485 (p300/CBP inhibitor). Deacetylation of GLUD1 by SIRT3 enhances its enzymatic activity and improves mitochondrial function and osteogenic differentiation. SENP1 knockdown blocks these effects. Western blot for acetylation, SENP1 knockdown, SIRT3 activity assays, osteogenic differentiation assays, in vivo OVX rat model Journal of orthopaedic surgery and research Low 40442713

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 The PLAG1-GDH1 Axis Promotes Anoikis Resistance and Tumor Metastasis through CamKK2-AMPK Signaling in LKB1-Deficient Lung Cancer. Molecular cell 269 29249655
2016 Structural basis for integration of GluD receptors within synaptic organizer complexes. Science (New York, N.Y.) 122 27418511
2014 Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 24872547
2000 Nerve tissue-specific (GLUD2) and housekeeping (GLUD1) human glutamate dehydrogenases are regulated by distinct allosteric mechanisms: implications for biologic function. Journal of neurochemistry 79 11032875
2017 A GluD Coming-Of-Age Story. Trends in neurosciences 77 28110935
2020 EGFR activates GDH1 transcription to promote glutamine metabolism through MEK/ERK/ELK1 pathway in glioblastoma. Oncogene 76 32034306
2021 GluD1 is a signal transduction device disguised as an ionotropic receptor. Nature 75 34135511
2009 Transgenic expression of Glud1 (glutamate dehydrogenase 1) in neurons: in vivo model of enhanced glutamate release, altered synaptic plasticity, and selective neuronal vulnerability. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 19890003
2009 Hyperinsulinism-hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations. European journal of endocrinology 71 19690084
1985 Nucleotide sequence of yeast GDH1 encoding nicotinamide adenine dinucleotide phosphate-dependent glutamate dehydrogenase. The Journal of biological chemistry 67 2989290
2014 GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells. European journal of human genetics : EJHG 60 24916645
2015 Essential role of GluD1 in dendritic spine development and GluN2B to GluN2A NMDAR subunit switch in the cortex and hippocampus reveals ability of GluN2B inhibition in correcting hyperconnectivity. Neuropharmacology 55 25721396
2017 GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons. Molecular psychiatry 49 28696429
2012 Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission. Journal of neurochemistry 48 22924626
2011 Induction of excitatory and inhibitory presynaptic differentiation by GluD1. Biochemical and biophysical research communications 48 22138648
2009 Human GLUD1 and GLUD2 glutamate dehydrogenase localize to mitochondria and endoplasmic reticulum. Biochemistry and cell biology = Biochimie et biologie cellulaire 47 19448744
2020 GluD1 knockout mice with a pure C57BL/6N background show impaired fear memory, social interaction, and enhanced depressive-like behavior. PloS one 46 32078638
1995 The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation. Molecular and cellular biology 45 7799961
2002 GDH1 expression is regulated by GLN3, GCN4, and HAP4 under respiratory growth. Biochemical and biophysical research communications 44 12054566
2002 Substitution of Ser for Arg-443 in the regulatory domain of human housekeeping (GLUD1) glutamate dehydrogenase virtually abolishes basal activity and markedly alters the activation of the enzyme by ADP and L-leucine. The Journal of biological chemistry 44 12324473
2020 Cryo-EM structures of the ionotropic glutamate receptor GluD1 reveal a non-swapped architecture. Nature structural & molecular biology 43 31925409
2018 Glutamate dehydrogenase (GLUD1) expression in breast cancer. Breast cancer research and treatment 39 30470977
2002 Unregulated elevation of glutamate dehydrogenase activity induces glutamine-stimulated insulin secretion: identification and characterization of a GLUD1 gene mutation and insulin secretion studies with MIN6 cells overexpressing the mutant glutamate dehydrogenase. Diabetes 39 11872671
2019 Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. The Journal of comparative neurology 38 31625608
2023 GluD1 binds GABA and controls inhibitory plasticity. Science (New York, N.Y.) 37 38060673
2011 Neuronal Glud1 (glutamate dehydrogenase 1) over-expressing mice: increased glutamate formation and synaptic release, loss of synaptic activity, and adaptive changes in genomic expression. Neurochemistry international 33 21397652
2022 EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer. Cell reports 31 36516759
2022 Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer. Cell death & disease 30 35595754
2012 The complex regulation of human glud1 and glud2 glutamate dehydrogenases and its implications in nerve tissue biology. Neurochemistry international 27 22658952
2021 Cytosolic GDH1 degradation restricts protein synthesis to sustain tumor cell survival following amino acid deprivation. The EMBO journal 26 34269483
2020 Methylcrotonoyl-CoA Carboxylase 2 Promotes Proliferation, Migration and Invasion and Inhibits Apoptosis of Prostate Cancer Cells Through Regulating GLUD1-P38 MAPK Signaling Pathway. OncoTargets and therapy 23 32801758
1993 Three human glutamate dehydrogenase genes (GLUD1, GLUDP2, and GLUDP3) are located on chromosome 10q, but are not closely physically linked. Genomics 22 8244384
2015 Expression of human GLUD1 and GLUD2 glutamate dehydrogenases in steroid producing tissues. Molecular and cellular endocrinology 21 26241911
2020 Hyperinsulinism associated with GLUD1 mutation: allosteric regulation and functional characterization of p.G446V glutamate dehydrogenase. Human genomics 19 32143698
2016 Widening Spectrum of Cellular and Subcellular Expression of Human GLUD1 and GLUD2 Glutamate Dehydrogenases Suggests Novel Functions. Neurochemical research 19 27422263
2013 Development of mice with brain-specific deletion of floxed glud1 (glutamate dehydrogenase 1) using cre recombinase driven by the nestin promoter. Neurochemical research 19 23595828
2024 GLUD1 inhibits hepatocellular carcinoma progression via ROS-mediated p38/JNK MAPK pathway activation and mitochondrial apoptosis. Discover oncology 17 38216781
2022 GLUD1 suppresses renal tumorigenesis and development via inhibiting PI3K/Akt/mTOR pathway. Frontiers in oncology 16 36203437
2015 Comparison of the Vidas C. difficile GDH Automated Enzyme-Linked Fluorescence Immunoassay (ELFA) with Another Commercial Enzyme Immunoassay (EIA) (Quik Chek-60), Two Selective Media, and a PCR Assay for gluD for Detection of Clostridium difficile in Fecal Samples. Journal of clinical microbiology 16 25788549
2023 STUB1-mediated ubiquitination regulates the stability of GLUD1 in lung adenocarcinoma. iScience 15 37416474
2022 Differences between the GluD1 and GluD2 receptors revealed by GluD1 X-ray crystallography, binding studies and molecular dynamics. The FEBS journal 14 36128700
2020 Ultrastructural localization of glutamate delta 1 (GluD1) receptor immunoreactivity in the mouse and monkey striatum. The Journal of comparative neurology 14 33084025
2014 Metabolism changes during aging in the hippocampus and striatum of glud1 (glutamate dehydrogenase 1) transgenic mice. Neurochemical research 14 24442550
2010 Hap2-3-5-Gln3 determine transcriptional activation of GDH1 and ASN1 under repressive nitrogen conditions in the yeast Saccharomyces cerevisiae. Microbiology (Reading, England) 14 21051484
2019 Mechanisms underlying the synaptic trafficking of the glutamate delta receptor GluD1. Molecular psychiatry 13 30824864
2024 GLUD1 determines murine muscle stem cell fate by controlling mitochondrial glutamate levels. Developmental cell 12 39121856
2023 GluD receptors are functional ion channels. Biophysical journal 12 37177782
2020 miR‑30a‑5p inhibits hypoxia/reoxygenation‑induced oxidative stress and apoptosis in HK‑2 renal tubular epithelial cells by targeting glutamate dehydrogenase 1 (GLUD1). Oncology reports 12 32945480
2014 Mutational analysis of ABCC8, KCNJ11, GLUD1, HNF4A and GCK genes in 30 Chinese patients with congenital hyperinsulinism. Endocrine journal 12 25008049
2013 Haplotype variation of Glu-D1 locus and the origin of Glu-D1d allele conferring superior end-use qualities in common wheat. PloS one 12 24098671
2024 Lack of evidence for direct ligand-gated ion channel activity of GluD receptors. Proceedings of the National Academy of Sciences of the United States of America 11 39052831
2023 Potentiation of neuronal activity by tonic GluD1 current in brain slices. EMBO reports 11 37154294
2024 GRID1/GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses. Molecular psychiatry 10 38418578
2024 Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis. Journal of molecular cell biology 10 38587834
2022 Mosaic GLUD1 Mutations Associated with Hyperinsulinism Hyperammonemia Syndrome. Hormone research in paediatrics 10 35952631
2022 Identification of Glu-D1 Alleles and Novel Marker-Trait Associations for Flour Quality and Grain Yield Traits under Heat-Stress Environments in Wheat Lines Derived from Diverse Accessions of Aegilops tauschii. International journal of molecular sciences 10 36233335
2020 Hyperinsulinism hyperammonaemia (HI/HA) syndrome due to GLUD1 mutation: phenotypic variations ranging from late presentation to spontaneous resolution. Journal of pediatric endocrinology & metabolism : JPEM 10 32229669
2019 Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1. Indian journal of pediatrics 10 31119523
2016 Hyperinsulinism-hyperammonemia syndrome: a de novo mutation of the GLUD1 gene in twins and a review of the literature. Journal of pediatric endocrinology & metabolism : JPEM 10 27383869
2024 Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death. Cell insight 9 39144257
1993 Chromosomal mapping of two members of the human glutamate dehydrogenase (GLUD) gene family to chromosomes 10q22.3-q23 and Xq22-q23. Human heredity 9 8288265
2011 Differential levels of glutamate dehydrogenase 1 (GLUD1) in Balb/c and C57BL/6 mice and the effects of overexpression of the Glud1 gene on glutamate release in striatum. ASN neuro 8 21446915
2002 The cytogenetics and molecular characteristics of a translocated chromosome 1AS.1AL-1DL with a Glu-D1 locus in durum wheat. Cellular & molecular biology letters 8 12378261
2001 A Japanese case of congenital hyperinsulinism with hyperammonemia due to a mutation in glutamate dehydrogenase (GLUD1) gene. Internal medicine (Tokyo, Japan) 8 11201367
1989 A restriction fragment length polymorphism at murine Glud locus co-segregates with Rib-1, Es-10, and Tcra on chromosome 14. Nucleic acids research 8 2566156
2025 D-Serine disrupts Cbln1 and GluD1 interaction and affects Cbln1-dependent synaptic effects and nocifensive responses in the central amygdala. Cellular and molecular life sciences : CMLS 7 39890638
1993 Structure and expression analysis of a member of the human glutamate dehydrogenase (GLUD) gene family mapped to chromosome 10p11.2. Human genetics 7 8314555
2025 Nuclear PHGDH regulates macrophage polarization through transcriptional repression of GLUD1 and GLS2 in breast cancer. Cancer biology & medicine 6 40434360
2016 2,3,7,8 Tetrachlorodibenzo-p-dioxin-induced RNA abundance changes identify Ackr3, Col18a1, Cyb5a and Glud1 as candidate mediators of toxicity. Archives of toxicology 6 27136898
2024 IDH2 and GLUD1 depletion arrests embryonic development through an H4K20me3 epigenetic barrier in porcine parthenogenetic embryos. Zoological research 5 39318125
2024 BET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer. Life metabolism 5 39872506
2019 The NADP+-dependent glutamate dehydrogenase Gdh1 is subjected to glucose starvation-induced reversible aggregation that affects stress resistance in yeast. Journal of microbiology (Seoul, Korea) 5 31376105
2015 Differential interaction of hGDH1 and hGDH2 with manganese: Implications for metabolism and toxicity. Neurochemistry international 5 25837286
2024 Dynamic behaviors of protein and water associated with fresh noodle quality during processing based on different HMW-GSs at Glu-D1. Food chemistry 4 38754351
2023 Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1. Endocrine connections 4 35951311
2023 Polymorphism and expression of GLUD1 in relation to reproductive performance in Jining Grey goats. Archives animal breeding 4 38205377
2022 Homecoming of the estranged GluD channels. Trends in neurosciences 4 35490056
2021 Structural biology and thermodynamics of GluD receptors. Neuropharmacology 4 33845075
2016 A novel mutation in the glutamate dehydrogenase (GLUD1) of a patient with congenital hyperinsulinism-hyperammonemia (HI/HA). Journal of pediatric endocrinology & metabolism : JPEM 4 26656609
2015 Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene. Journal of pediatric endocrinology & metabolism : JPEM 4 25781533
2011 Biochemical evaluation of an infant with hypoglycemia resulting from a novel de novo mutation of the GLUD1 gene and hyperinsulinism-hyperammonemia syndrome. Journal of pediatric endocrinology & metabolism : JPEM 4 21932603
2025 A-485 alleviates postmenopausal osteoporosis by activating GLUD1 deacetylation through the SENP1-Sirt3 signal pathway. Journal of orthopaedic surgery and research 3 40442713
2021 Diazoxide-Induced Neutropenia and Long-Term Follow-up in a Patient with Hyperinsulinemia-Hyperammonemia due to GLUD1 Mutation. Acta endocrinologica (Bucharest, Romania : 2005) 3 35342475
2016 A novel mutation in GLUD1 causing hyperinsulinism-hyperammonemia in a patient with high density of homozygosity on microarray: a case report. Journal of medical case reports 3 26839063
2015 Characterization of a thermostable glucose dehydrogenase with strict substrate specificity from a hyperthermophilic archaeon Thermoproteus sp. GDH-1. Bioscience, biotechnology, and biochemistry 3 25746627
2025 GluD1 at the synaptic crossroads: from domain structure to circuit dysfunction. Acta pharmacologica Sinica 2 41345253
2024 GDH1 exacerbates renal fibrosis by inhibiting the transcriptional activity of peroxisome proliferator-activated receptor gamma. The FEBS journal 2 39136063
2024 Energy metabolism-related GLUD1 contributes to favorable clinical outcomes of IDH-mutant glioma. BMC neurology 2 39272024
2023 UBE3A and transsynaptic complex NRXN1-CBLN1-GluD1 in a hypothalamic VMHvl-arcuate feedback circuit regulates aggression. bioRxiv : the preprint server for biology 2 36909588
2017 [Effect of GLUD1 on proliferation, osteogenic differentiation and mineralization of human dental pulp stem cells]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 2 29199326
2023 Increases in anterograde axoplasmic transport in neurons of the hyper-glutamatergic, glutamate dehydrogenase 1 (Glud1) transgenic mouse: Effects of glutamate receptors on transport. Journal of neurochemistry 1 38124277
2013 [ABCC8, KCNJ11 and GLUD1 gene mutation analysis in congenital hyperinsulinism pedigree]. Zhonghua yi xue za zhi 1 23902843
2026 Integrated network pharmacology and multi-omics reveals GLUD1-mediated α-KG/Glu conversion in regulating amino acid metabolism: a mechanism of Dangua Fang against type 2 diabetes mellitus. Journal of ethnopharmacology 0 41529805
2026 GLUD1 supports ovarian cancer progression by counteracting anoikis via ARAF/MEK/ERK signaling. NPJ precision oncology 0 41786885
2026 AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression. Cell death & disease 0 41876450
2026 Echinacoside modulates PARP14-GLUD1 axis to mediate energy metabolism reprogramming and mitochondrial function in diminished ovarian reserve. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41895093
2026 Chronic stress promotes oral squamous cell carcinoma progression via GLUD1-mediated metabolic reprogramming. Carcinogenesis 0 41973845
2025 Hyperinsulinism-hyperammonemia syndrome associated with GLUD1 gene mutation: a case series. Journal of medical case reports 0 40652260
2023 Structural insights into the ligand binding domain of GluD1 and GluD2 receptors. The FEBS journal 0 37345272
2010 [Mutation analysis of the GLUD1 gene in patients with glutamate dehydrogenase congenital hyperinsulinism]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 20931523

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