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Last update 08 May 2025

GLUL

Last update 08 May 2025

Basic Info

Synonyms

GLNS, GLUL, Glutamate--ammonia ligase

+ [4]

Introduction

Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:16267323, PubMed:30158707, PubMed:36289327). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351). Through the interaction with BEST2, inhibits BEST2 channel activity by affecting the gating at the aperture in the absence of intracellular L-glutamate, but sensitizes BEST2 to intracellular L-glutamate, which promotes the opening of BEST2 and thus relieves its inhibitory effect on BEST2 (PubMed:36289327).

Drugs associated with GLUL

WO2024227949

Patent Mining

Target

GLUL

Mechanism-

Active Org.

Max Planck Gesellschaft zur Förderung der Wissenschaften eV

Originator Org.

Max Planck Gesellschaft zur Förderung der Wissenschaften eV

Active Indication

Cardiovascular Diseases [+12]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GLUL

100 Translational Medicine associated with GLUL

0 Patents (Medical) associated with GLUL

11,004

Literatures (Medical) associated with GLUL

01 Dec 2025·Current Neurology and Neuroscience Reports

Hepatic Encephalopathy: Current Thoughts on Pathophysiology and Management

Review

Author: Pan, Kausik ; Chakravarty, Ambar ; Sen, Barun Kumar

PURPOSE OF REVIEWThis review highlights the causes, types and clinical staging of hepatic encephalopathy (HE). Current concepts on the probable pathogenetic mechanisms and currently practiced therapeutic options are discussed.RECENT FINDINGSHE may be covert and overt. Also known as minimal HE. Covert HE, where there are behavioral abnormalities and impairment in activities of daily living with intact sensorium. The pathophysiology of HE remains poorly understood. There is disturbance of the urea cycle due to liver disease leading to increased production of ammonia. The ammonium ion enters the astrocytes along with glutamate (converted to glutamine by ammonia) and myo-inositol, thereby increasing the osmolality of the astrocytic cytoplasm. This osmotic gradient results in accumulation of water inside the astrocytes resulting in cerebral edema and increase in brain volume. Additionally, current research has noted the role of cerebral oxidative/nitrosative stress and the synergistic effects of increased cerebral ammonia and alteration in neurotransmitters, neurometabolites, and cortical excitability due to systemic inflammation. In advanced liver disease with systemic infection or inflammation, neuroinflammatory processes play significant role in the development of HE. Inflammatory cytokines like TNF-α, IL-6, IL-17 in presence of hyperammonemia have been found to induce neurotoxicity of ammonia by passing through the blood brain barrier and causing enlarged/swollen pale astrocytes, resulting in HE. Disrupted enterohepatic circulation in end stage liver disease also causes elevation of bile acids which induces neuroinflammation. Manganese and zinc play as co-factors of enzymatic reaction. These metal deposition causes multiple psychomotor symptoms observed in HE. The gut environment has a major impact on brain function in patients with HE. Toxins such as ammonia and inflammatory cytokines produced by this impaired intestinal flora access the circulation through porto-systemic anastomoses and exacerbate or precipitate HE. Finally, as a result of recurrent cerebral edema from astrocytic dysfunction and neuroinflammation, permanent neurodegeneration occurs with cognitive decline and motor disturbances, especially parkinsonian features and gait disturbances. This is the stage of chronic hepatic encephalopathy. Currently L-ornithine L-aspartate (LOLA) is being used to lower the ammonia level by stimulating the urea cycle. HE comprises a broad spectrum of neurological and/or psychiatric abnormalities caused by hepatic insufficiency and/or portal-systemic shunting in the absence of any other causes of brain dysfunction. HE may be caused or precipitated by several factors like infections, intoxications and drugs. The encephalopathic features may be covert or overt. The pathogenetic mechanisms for HE may be different. In the presence of liver disease, HE primarily results from disturbed urea cycle with hyperammonemia causing astrocytic swelling and cerebral edema. Porto-systemic anastomoses with intact liver function can cause HE by allowing ammonia and other toxins produced by the gut microbial flora and allowing these to bypass detoxification by the liver and exposing the brain to their harmful effects. Principles of therapy are twofold. First protecting the liver and the brain from gut generated ammonia and other toxins by ensuring smooth bowel function and avoiding stagnation with the use of osmotic laxatives like lactulose or lactitol and also reducing the gut microbial load with use of anti-bacterials/bacteriophages like neomycin and rifaximin along with metronidazole. Second, reducing the already generated cerebral edema by use of mannitol and appropriate ventilatory support. Currently L-ornithine L-aspartate (LOLA) is being used to reduce the ammonia load to the liver. LOLA is a stable compound formed from two amino acids. L-ornithine plays a crucial role in stimulating the urea cycle, leading to a reduction in ammonia levels. Both L-ornithine and L-aspartate serve as substrates for the enzyme glutamate transaminase, and their administration results in elevated glutamate concentrations. Ammonia is subsequently utilized in the conversion of glutamate to glutamine through the action of glutamine synthetase. Finally in resistant cases the use of liver transplant needs to be considered. Alternatively extracorporeal liver assist devices may be used like Molecular Adsorbent Recirculating System (MARS) or Single-Pass Albumin Dialysis (SPAD).

01 Sep 2025·Comparative Biochemistry and Physiology Part D: Genomics and Proteomics

Comparative transcriptome sequencing of two shell colour variants of Haliotis discus hannai identifying genes involved in shell formation and photosensitivity

Article

Author: Zhang, Xuekai ; Liu, Kun ; Li, Qianqian ; Yuan, Mengqiang ; Zhang, Meiwei ; Guo, Wenjian ; Wang, Xiaotong ; Wang, Xiaona ; Liu, Tianshuo

Shell colour variation in Haliotis discus hannai is a complex trait influenced by genetic, physiological, and environmental factors. This study investigates the molecular mechanisms underlying shell colour formation, with a focus on the roles of biomineralisation, photosensitivity, and stress resistance. Using transcriptome analysis and microstructural observations, we compared red-shelled (RS) and green-shelled (GS) variants to identify key genes and pathways associated with shell colour. The results reveal that GS variants exhibit higher expression of visual protein genes (e.g., RHO-opnGq), which are linked to light sensitivity and pigment synthesis. Additionally, RS variants show upregulated chitin biosynthesis genes (e.g., CHs-IA), potentially influencing shell structure and pigmentation. These findings suggest that these genes play a critical role in regulating pigment deposition and shell colour formation, while biomineralisation genes contribute to shell integrity. This study provides new insights into the genetic basis of shell colour variation and its ecological significance, offering valuable information for selective breeding programs.

01 Jul 2025·Brain, Behavior, and Immunity

Inflammation and psychomotor retardation in depression: The moderating role of glymphatic system

Article

Author: Li, Ying ; Qiu, Yingwei ; Zhang, Yingli ; Zhou, Zhifeng ; Liang, Qunjun ; Lin, Shiwei ; Xu, Ziyun ; Chen, Shengli ; Peng, Bo ; Wei, Hongyue ; Lin, Xiaoshan ; Hou, Gangqiang

BACKGROUNDPsychomotor retardation (PMR) is a predominant symptom in patients with major depressive disorder (MDD). The relationship between inflammation and PMR is the subject of ongoing debate. The glymphatic system (GS) is a waste clearance system in the brain that interacts with the immune system. Herein, we hypothesized that GS function moderates the association between inflammation and PMR.METHODSA total of 67 patients with MDD and 67 healthy controls (HCs) were recruited and underwent MRI scanning. PMR and inflammation, which were evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in peripheral blood, were assessed in all patients. Diffusion tensor imaging analysis along the perivascular space was used to assess GS function. Functional connectivity (FC) and morphology within the motor circuit were also assessed. Moderation models were constructed to estimate the effect of GS function as a moderator of the relationships between hsCRP level and PMR and between hsCRP level and motor cortex FC and morphology.RESULTSGS function in patients was impaired compared with that in HCs (t = -2.635, p = 0.009). Moderation models showed that hsCRP level significantly aggravated PMR severity at low levels of GS function, whereas this effect was negligible in patients with optimal GS function (F = 6.725, p = 0.021). GS function also exhibited a moderation effect on inflammation-related alterations in morphology (F = 13.86, p = 0.047) and FC (F = 13.765, p < 0.001) in the motor circuit.CONCLUSIONA well-functioning GS mitigates inflammation-induced PMR and protects neurons from inflammatory damage. Given its moderating effect, GS function may play a crucial role in MDD psychopathology, and targeting GS function may have therapeutic value as an MDD treatment strategy.

News (Medical) associated with GLUL

19 Nov 2024

·www.businesswire.com

Asimov and RevOpsis Therapeutics Sign Licensing Agreement for High Titer Multispecific-Expressing Cell Line

BOSTON & SAN CARLOS, Calif.--( BUSINESS WIRE )--Asimov, the synthetic biology company advancing the design and manufacture of therapeutics, today announced a licensing agreement for its CHO Edge System with RevOpsis Therapeutics (“RevOpsis”), a next-generation biopharmaceutical company spearheading innovation of multispecific biologics in ophthalmic therapies. This agreement follows a successful cell line development campaign with Asimov’s CHO Edge System for the lead RevOpsis asset, RO-104. Under the terms of the agreement, RevOpsis will integrate the CHO Edge System in the development and commercialization of its first-in-class fully modular tri-specific biologic, RO-104, for the treatment of retinal vascular diseases. RO-104 is designed to address all three clinically validated dominant angiogenic pathways (VEGF-A, VEGF-C, Ang-2) implicated in retinal vascular disease progression, including neovascular AMD and diabetic macular edema. RevOpsis has made significant progress with clinical progression of RO-104 supporting the initiation of IND-enabling studies beginning in January 2025 The CHO Edge System incorporates a GMP-banked CHO-K1 glutamine synthetase (GS) knockout host – or alternatively a GS-Fut8 double knockout for producing afucosylated antibodies – along with a hyperactive transposase, a library of over one thousand characterized genetic parts for vector design, and advanced AI and biophysics models. The system reliably generates stable cell lines with high titer and exceptional product quality, enabling optimization of the expression vector and bioreactor processes across various biologics modalities. Alec Nielsen, Asimov co-founder and CEO, said: “ Asimov’s CHO Edge System continues to gain rapid adoption since its launch last year. We are delighted that RevOpsis is joining the growing set of partners that are putting their trust in our platform. CHO Edge will form the cornerstone of their bioproduction process for an impactful therapeutic that will serve unmet needs in a growing patient population. We look forward to supporting their biologic development as they progress through clinical trials.” Ramanath Bhandari, RevOpsis co-founder and CEO, commented: “ RevOpsis is committed to the rapid discovery and development of novel multispecific therapies utilizing our modular RevMod™ Platform that consists of fully-human libraries. Asimov’s CHO Edge System has exhibited great performance and will underpin the development and commercialization of our lead clinical asset RO-104 for the treatment of retinal vascular disease progression, including neovascular age-related macular degeneration.” To learn more about the CHO Edge System, please visit Asimov’s webpage at https://www.asimov.com/cho

License out/in

28 Oct 2024

·www.prnewswire.com

WuXi Biologics Launches WuXia™ RidGS for Non-Antibiotic Cell Line Development

SHANGHAI, Oct. 28, 2024 /PRNewswire/ -- WuXi Biologics ("WuXi Bio") (2269.HK), a leading global Contract Research, Development, and Manufacturing Organization (CRDMO), today announced the launch of WuXia™ RidGS, a high-yield glutamine synthetase (GS)-knockout Chinese hamster ovary (CHO) expression system platform. The platform, specialized in non-antibiotic cell line development, employs zinc finger nucleases (ZFN) technology for targeted knockout of the endogenous GS gene in CHO cells. Based on the WuXia™ platform, WuXia™ RidGS not only retains the robust cell growth, metabolism, and expression profile characteristic of WuXia™, but also boasts an average clonal expression level exceeding 6 g/L for monoclonal antibodies(mAbs). WuXia™ RidGS ensures cell line stability for mAbs, as well as for various other therapeutic modalities, including bispecific antibodies, Fc-fusion proteins, and recombinant proteins. The quality of protein products expressed by the platform showcases favorable glycosylation patterns while maintaining an exceptional purity profile. In addition, without the need for antibiotics, WuXia™ RidGS host and production cells consistently maintain stable productivity and uniform product quality throughout extensive, long-term cell line stability studies. Dr. Chris Chen, CEO of WuXi Biologics, commented, "With the launch of WuXia™ RidGS, we are pleased to offer a more efficient alternative for the development of advanced therapeutic proteins. WuXi Biologics continues its commitment to developing tailored technology platforms that cater to the evolving needs of our global clients, accelerating the speed to market for life-saving therapies and advancing the accessibility of high-quality biologics for patients worldwide." About the WuXia ™ Cell Line Development Platform Family WuXia™ is a proven, high-yielding (up to about 11 g/L) mammalian cell line platform developed by WuXi Biologics. Accepted by regulatory agencies worldwide, the WuXia™ platform has generated over 900 cell lines expressing monoclonal and bispecific antibodies, fusion proteins, enzymes and other recombinant proteins for clinical and commercial manufacturing. WuXiaADCC Plus™ and WuXia™ RidGS mirror the impressive attributes of WuXia™, while catering to the diverse needs of global customers. About WuXi Biologics WuXi Biologics (stock code: 2269.HK) is a leading global Contract Research, Development and Manufacturing Organization (CRDMO) offering end-to-end solutions that enable partners to discover, develop and manufacture biologics – from concept to commercialization – for the benefit of patients worldwide. With over 12,000 skilled employees in China, the United States, Ireland, Germany and Singapore, WuXi Biologics leverages its technologies and expertise to provide customers with efficient and cost-effective biologics discovery, development and manufacturing solutions. As of June 30, 2024, WuXi Biologics is supporting 742 integrated client projects, including 16 in commercial manufacturing (excluding COVID CMO and non-COVID dormant CMO projects). WuXi Biologics views Environmental, Social, and Governance (ESG) responsibilities as an integral component of our ethos and business strategy, and we aim to become an ESG leader in the biologics CRDMO sector. Our facilities use next-generation biomanufacturing technologies and clean-energy sources. We have also established an ESG committee led by our CEO to steer the comprehensive ESG strategy and its implementation, enhancing our commitment to sustainability. For more information about WuXi Biologics, please visit: SOURCE WuXi Biologics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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GLUL

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