bims-glucam Biomed News
on Glutamine cancer metabolism
Issue of 2024‒06‒09
fifteen papers selected by
Sreeparna Banerjee, Middle East Technical University
  1. The role of anaplerotic metabolism of glucose and glutamine in insulin secretion: A model approach.
  2. Glutamine-derived peptides: Current progress and future directions.
  3. Necroptosis-Mediated Synergistic Photodynamic and Glutamine-Metabolic Therapy Enabled by a Biomimetic Targeting Nanosystem for Cholangiocarcinoma.
  4. Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma.
  5. Emerging roles of long noncoding RNAs in enzymes related intracellular metabolic pathways in cancer biology.
  6. Strategic disruption of cancer's powerhouse: precise nanomedicine targeting of mitochondrial metabolism.
  7. UnitedMet harnesses RNA-metabolite covariation to impute metabolite levels in clinical samples.
  8. Effects of essential amino acid (EAA) and glutamine supplementation on skeletal muscle wasting in acute, subacute, and postacute conditions.
  9. Ovarian aging: energy metabolism of oocytes.
  10. SLC7A11-mediated cystine import protects against NDUFS7 deficiency-induced cell death in HEK293T cells.
  11. Metabolic availability of amino acids in humans.
  12. Protocol for separating cancer cell subpopulations by metabolic activity using flow cytometry.
  13. Unraveling metabolic characteristics and clinical implications in gastric cancer through single-cell resolution analysis.
  14. A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases.
  15. Glutathione‑degrading enzymes in the complex landscape of tumors (Review).
  1. Biophys Chem. 2024 May 23. pii: S0301-4622(24)00099-1. [Epub ahead of print]311 107270
    The role of anaplerotic metabolism of glucose and glutamine in insulin secretion: A model approach.
    Vladimir Grubelnik, Jan Zmazek, Marko Gosak, Marko Marhl.
      We propose a detailed computational beta cell model that emphasizes the role of anaplerotic metabolism under glucose and glucose-glutamine stimulation. This model goes beyond the traditional focus on mitochondrial oxidative phosphorylation and ATP-sensitive K+ channels, highlighting the predominant generation of ATP from phosphoenolpyruvate in the vicinity of KATP channels. It also underlines the modulatory role of H2O2 as a signaling molecule in the first phase of glucose-stimulated insulin secretion. In the second phase, the model emphasizes the critical role of anaplerotic pathways, activated by glucose stimulation via pyruvate carboxylase and by glutamine via glutamate dehydrogenase. It particularly focuses on the production of NADPH and glutamate as key enhancers of insulin secretion. The predictions of the model are consistent with empirical data, highlighting the complex interplay of metabolic pathways and emphasizing the primary role of glucose and the facilitating role of glutamine in insulin secretion. By delineating these crucial metabolic pathways, the model provides valuable insights into potential therapeutic targets for diabetes.
    Keywords:  GSH; Isocitrate/α-KG (IDH) shuttle; Mathematical model; NADPH; PEP cycle; Pancreatic beta cell; Pyruvate-malate cycle; ROS; SENP1
    DOI:  https://doi.org/10.1016/j.bpc.2024.107270
  2. Compr Rev Food Sci Food Saf. 2024 Jul;23(4): e13386
    Glutamine-derived peptides: Current progress and future directions.
    Tianfei Yu, Tianshuo Hu, Kai Na, Li Zhang, Shuang Lu, Xiaohua Guo.
      Glutamine, the most abundant amino acid in the body, plays a critical role in preserving immune function, nitrogen balance, intestinal integrity, and resistance to infection. However, its limited solubility and instability present challenges for its use a functional nutrient. Consequently, there is a preference for utilizing glutamine-derived peptides as an alternative to achieve enhanced functionality. This article aims to review the applications of glutamine monomers in clinical, sports, and enteral nutrition. It compares the functional effectiveness of monomers and glutamine-derived peptides and provides a comprehensive assessment of glutamine-derived peptides in terms of their classification, preparation, mechanism of absorption, and biological activity. Furthermore, this study explores the potential integration of artificial intelligence (AI)-based peptidomics and synthetic biology in the de novo design and large-scale production of these peptides. The findings reveal that glutamine-derived peptides possess significant structure-related bioactivities, with the smaller molecular weight fraction serving as the primary active ingredient. These peptides possess the ability to promote intestinal homeostasis, exert hypotensive and hypoglycemic effects, and display antioxidant properties. However, our understanding of the structure-function relationships of glutamine-derived peptides remains largely exploratory at current stage. The combination of AI based peptidomics and synthetic biology presents an opportunity to explore the untapped resources of glutamine-derived peptides as functional food ingredients. Additionally, the utilization and bioavailability of these peptides can be enhanced through the use of delivery systems in vivo. This review serves as a valuable reference for future investigations of and developments in the discovery, functional validation, and biomanufacturing of glutamine-derived peptides in food science.
    Keywords:  artificial intelligence; bioactivity; de novo design and mass production; glutamine; peptide
    DOI:  https://doi.org/10.1111/1541-4337.13386
  3. Adv Sci (Weinh). 2024 Jun 05. e2309203
    Necroptosis-Mediated Synergistic Photodynamic and Glutamine-Metabolic Therapy Enabled by a Biomimetic Targeting Nanosystem for Cholangiocarcinoma.
    Qichang Zheng, Tianhao Zou, Weimin Wang, Chen Zhang, Shaobo Hu, Xiang Cheng, Ran Liu, Guoliang Wang, Ping Sun, Xing Zhou, Bing Yang, Jianjun Xu, Yang Gao, Jinyang Gu.
      Targeted delivery of glutamine metabolism inhibitors holds promise for cholangiocarcinoma therapy, yet effective delivery vehicles remain a challenge. This study reports the development of a biomimetic nanosystem, termed R-CM@MSN@BC, integrating mesoporous organosilicon nanoparticles with reactive oxygen species-responsive diselenide bonds for controlled release of the glutamine metabolism inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) and the photosensitizer Ce6. Erythrocyte membrane coating, engineered with Arg-Gly-Asp (RGD) peptides, not only enhanced biocompatibility but also improved tumor targeting and tissue penetration. Upon laser irradiation, R-CM@MSN@BC executed both photodynamic and glutamine-metabolic therapies, inducing necroptosis in tumor cells and triggering significant immunogenic cell death. Time-of-flight mass cytometry analysis revealed that R-CM@MSN@BC can remodel the immunosuppressive tumor microenvironment by polarizing M1-type macrophages, reducing infiltration of M2-type and CX3CR1+ macrophages, and decreasing T cell exhaustion, thereby increasing the effectiveness of anti-programmed cell death ligand 1 immunotherapy. This strategy proposed in this study presents a viable and promising approach for the treatment of cholangiocarcinoma.
    Keywords:  cancer immunotherapy; cholangiocarcinoma; diselenide‐bond bridged mesoporous organosilica nanoparticles; glutamine‐metabolic therapy; necroptosis; tumor‐associated macrophages
    DOI:  https://doi.org/10.1002/advs.202309203
  4. Rev Neurosci. 2024 Jun 07.
    Metabolic dysregulation of tricarboxylic acid cycle and oxidative phosphorylation in glioblastoma.
    Cristina Trejo-Solís, Norma Serrano-García, Rosa Angelica Castillo-Rodríguez, Diana Xochiquetzal Robledo-Cadena, Dolores Jimenez-Farfan, Álvaro Marín-Hernández, Daniela Silva-Adaya, Citlali Ekaterina Rodríguez-Pérez, Juan Carlos Gallardo-Pérez.
      Glioblastoma multiforme (GBM) exhibits genetic alterations that induce the deregulation of oncogenic pathways, thus promoting metabolic adaptation. The modulation of metabolic enzyme activities is necessary to generate nucleotides, amino acids, and fatty acids, which provide energy and metabolic intermediates essential for fulfilling the biosynthetic needs of glioma cells. Moreover, the TCA cycle produces intermediates that play important roles in the metabolism of glucose, fatty acids, or non-essential amino acids, and act as signaling molecules associated with the activation of oncogenic pathways, transcriptional changes, and epigenetic modifications. In this review, we aim to explore how dysregulated metabolic enzymes from the TCA cycle and oxidative phosphorylation, along with their metabolites, modulate both catabolic and anabolic metabolic pathways, as well as pro-oncogenic signaling pathways, transcriptional changes, and epigenetic modifications in GBM cells, contributing to the formation, survival, growth, and invasion of glioma cells. Additionally, we discuss promising therapeutic strategies targeting key players in metabolic regulation. Therefore, understanding metabolic reprogramming is necessary to fully comprehend the biology of malignant gliomas and significantly improve patient survival.
    Keywords:  glioma; metabolism; oncogenic signaling pathways
    DOI:  https://doi.org/10.1515/revneuro-2024-0054
  5. Biomed Pharmacother. 2024 Jun 01. pii: S0753-3322(24)00715-7. [Epub ahead of print]176 116831
    Emerging roles of long noncoding RNAs in enzymes related intracellular metabolic pathways in cancer biology.
    Jing Yu, Yue Zhang, Yaqi Xue, Hailong Pei, Bingyan Li.
      Metabolic reprogramming plays critical roles in the development and progression of tumor by providing cancer cells with a sufficient supply of nutrients and other factors needed for fast-proliferating. Emerging evidence indicates that long noncoding RNAs (lncRNAs) are involved in the initiation of metastasis via regulating the metabolic reprogramming in various cancers. In this paper, we aim to summarize that lncRNAs could participate in intracellular nutrient metabolism including glucose, amino acid, lipid, and nucleotide, regardless of whether lncRNAs have tumor-promoting or tumor-suppressor function. Meanwhile, modulation of lncRNAs in glucose metabolic enzymes in glycolysis, pentose phosphate pathway and tricarboxylic acid cycle (TCA) in cancer is reviewed. We also discuss therapeutic strategies targeted at interfering with enzyme activity to decrease the utilization of glucoses, amino acid, nucleotide acid and lipid in tumor cells. This review focuses on our current understanding of lncRNAs participating in cancer cell metabolic reprogramming, paving the way for further investigation into the combination of such approaches with existing anti-cancer therapies.
    Keywords:  Cancer; Intracellular nutrient metabolism; LncRNAs; Metabolic enzymes
    DOI:  https://doi.org/10.1016/j.biopha.2024.116831
  6. J Nanobiotechnology. 2024 Jun 08. 22(1): 318
    Strategic disruption of cancer's powerhouse: precise nanomedicine targeting of mitochondrial metabolism.
    Pei Lin, Ye Lu, Jiarong Zheng, Yunfan Lin, Xinyuan Zhao, Li Cui.
      Mitochondria occupy a central role in the biology of most eukaryotic cells, functioning as the hub of oxidative metabolism where sugars, fats, and amino acids are ultimately oxidized to release energy. This crucial function fuels a variety of cellular activities. Disruption in mitochondrial metabolism is a common feature in many diseases, including cancer, neurodegenerative conditions and cardiovascular diseases. Targeting tumor cell mitochondrial metabolism with multifunctional nanosystems emerges as a promising strategy for enhancing therapeutic efficacy against cancer. This review comprehensively outlines the pathways of mitochondrial metabolism, emphasizing their critical roles in cellular energy production and metabolic regulation. The associations between aberrant mitochondrial metabolism and the initiation and progression of cancer are highlighted, illustrating how these metabolic disruptions contribute to oncogenesis and tumor sustainability. More importantly, innovative strategies employing nanomedicines to precisely target mitochondrial metabolic pathways in cancer therapy are fully explored. Furthermore, key challenges and future directions in this field are identified and discussed. Collectively, this review provides a comprehensive understanding of the current state and future potential of nanomedicine in targeting mitochondrial metabolism, offering insights for developing more effective cancer therapies.
    Keywords:  Cancer therapy; Metabolism; Mitochondria; Nanomedicine
    DOI:  https://doi.org/10.1186/s12951-024-02585-3
  7. medRxiv. 2024 May 25. pii: 2024.05.24.24307903. [Epub ahead of print]
    UnitedMet harnesses RNA-metabolite covariation to impute metabolite levels in clinical samples.
    Amy X Xie, Wesley Tansey, Ed Reznik.
      Comprehensively studying metabolism requires the measurement of metabolite levels. However, in contrast to the broad availability of gene expression data, metabolites are rarely measured in large molecularly-defined cohorts of tissue samples. To address this basic barrier to metabolic discovery, we propose a Bayesian framework ("UnitedMet") which leverages the empirical strength of RNA-metabolite covariation to impute otherwise unmeasured metabolite levels from widely available transcriptomic data. We demonstrate that UnitedMet is equally capable of imputing whole pool sizes as well as the outcomes of isotope tracing experiments. We apply UnitedMet to investigate the metabolic impact of driver mutations in kidney cancer, identifying a novel association between BAP1 and a highly oxidative tumor phenotype. We similarly apply UnitedMet to determine that advanced kidney cancers upregulate oxidative phosphorylation relative to early-stage disease, that oxidative metabolism in kidney cancer is associated with inferior outcomes to combination therapy, and that kidney cancer metastases themselves demonstrate elevated oxidative phosphorylation relative to primary tumors. UnitedMet therefore enables the assessment of metabolic phenotypes in contexts where metabolite measurements were not taken or are otherwise infeasible, opening new avenues for the generation and evaluation of metabolite-centered hypotheses. UnitedMet is open source and publicly available ( https://github.com/reznik-lab/UnitedMet ).
    DOI:  https://doi.org/10.1101/2024.05.24.24307903
  8. Clin Nutr ESPEN. 2024 May 28. pii: S2405-4577(24)00142-6. [Epub ahead of print]62 224-233
    Effects of essential amino acid (EAA) and glutamine supplementation on skeletal muscle wasting in acute, subacute, and postacute conditions.
    Massimo Negro, Oscar Crisafulli, Giuseppe D'Antona.
      Under optimal physiological conditions, muscle mass maintenance is ensured by dietary protein, which balances the amino acid loss during the post-absorption period and preserves the body's protein homeostasis. Conversely, in critical clinical conditions (acute, subacute or postacute), particularly those related to hypomobility or immobility, combined with malnutrition, and local/systemic inflammation, the loss of muscle mass and strength can be quantitatively significant. A decline of more than 1% in muscle mass and of more than 3% in muscle strength has been registered in subjects with aged 20-37 yr after just five days of bed rest, similarly to those observed during one year of age-related decline in individuals over the age of 50. Loss of muscle mass and strength can have a dramatic effect on subjects' functional capacities, on their systemic metabolic control and on the amino acid reserve function, all of which are fundamental for the maintenance of other organs' and tissues' cell processes. References available indicate that the average 1%-2% reduction per day of muscle mass in patients in the intensive care unit (ICU) could represent an independent predictor of hospital mortality and physical disability in the five years following hospitalization. After just a few days or weeks of administration, supplementation with EAAs and glutamine has shown significant effects in maintaining muscle size and strength, which are typically negatively affected by some acute/subacute or postacute critical conditions (muscle recovery after surgery, oncology patients, ICU treatments), especially in the elderly or in those with pre-existing degenerative diseases. In this review, we focused on the theoretical bases and the most relevant clinical studies of EAA and glutamine supplementation as a single compound, with the aim of clarifying whether their combined use in a blend (EAAs-glutamine) could be potentially synergistic to prevent disease-related muscle wasting and its impact on the duration and quality of patients' clinical course.
    Keywords:  Cancer cachexia; Essential amino acids; Glutamine; Intensive care unit; Malnutrition; Muscle recovery
    DOI:  https://doi.org/10.1016/j.clnesp.2024.05.023
  9. J Ovarian Res. 2024 May 31. 17(1): 118
    Ovarian aging: energy metabolism of oocytes.
    Shenglan Bao, Tailang Yin, Su Liu.
      In women who are getting older, the quantity and quality of their follicles or oocytes and decline. This is characterized by decreased ovarian reserve function (DOR), fewer remaining oocytes, and lower quality oocytes. As more women choose to delay childbirth, the decline in fertility associated with age has become a significant concern for modern women. The decline in oocyte quality is a key indicator of ovarian aging. Many studies suggest that age-related changes in oocyte energy metabolism may impact oocyte quality. Changes in oocyte energy metabolism affect adenosine 5'-triphosphate (ATP) production, but how related products and proteins influence oocyte quality remains largely unknown. This review focuses on oocyte metabolism in age-related ovarian aging and its potential impact on oocyte quality, as well as therapeutic strategies that may partially influence oocyte metabolism. This research aims to enhance our understanding of age-related changes in oocyte energy metabolism, and the identification of biomarkers and treatment methods.
    Keywords:  Adenosine Remedial Pathway; Diminished ovarian reserve; Glutamine metabolism; Lipid metabolism; Metabolism; OXPHOS; Oocyte; Ovarian aging; TCA cycle
    DOI:  https://doi.org/10.1186/s13048-024-01427-y
  10. Biochem Biophys Res Commun. 2024 May 29. pii: S0006-291X(24)00714-9. [Epub ahead of print]723 150178
    SLC7A11-mediated cystine import protects against NDUFS7 deficiency-induced cell death in HEK293T cells.
    Jieli Chen, Liuze Gao.
      Cell models of mitochondrial complex Ⅰ (CⅠ) deficiency display significant elevations in reactive oxygen species (ROS) levels and an increase in cellular apoptosis. However, the underlying mechanisms governing anti-apoptotic processes in CⅠ-deficient cells remain elusive. Here, we introduced a mutation in NDUFS7, a crucial subunit of CI, in HEK293T cells and found that the absence of NDUFS7 resulted in reduced cell proliferation, elevated cell death, and increased susceptibility to oxidative stress. Mechanismly, we revealed that the upregulation of SLC7A11 played a crucial role in mitigating cell death resulting from NDUFS7 deficiency. Specifically, the increased expression of SLC7A11 enhanced cystine import, which subsequently reduced cell death by promoting the biosynthesis of reduced glutathione (GSH). Collectively, our findings suggest that SLC7A11-mediated cystine import, representing a novel pathway independent of NADPH production, plays a vital role in protection against NDUFS7 deficiency-induced cell death. This novel pathway provides potential insights into the understanding of pathogenic mechanisms and the therapeutic management of mitochondrial disorders associated with CⅠ deficiency.
    Keywords:  Cell death; Cystine; Deficiency; NDUFS7; SLC7A11
    DOI:  https://doi.org/10.1016/j.bbrc.2024.150178
  11. Front Nutr. 2024 ;11 1400676
    Metabolic availability of amino acids in humans.
    Alyssa Paoletti, Rajavel Elango, Glenda Courtney-Martin.
      Knowledge of amino acid bioavailability and the effect of combining complementary protein sources are required to determine how to best meet an individual's protein and indispensable amino acid needs. Traditionally, protein quality of foods has been assessed using digestibility data. Digestibility may overestimate bioavailability of some amino acids particularly those more susceptible to heat and processing. The indicator amino acid oxidation (IAAO) method has been validated and applied to determine amino acid bioavailability termed metabolic availability of the first limiting amino acid of a proteinaceous food. The metabolic availability of the limiting amino acid in the test protein is determined as a ratio of the indicator amino acid oxidation response to graded intakes of the test protein compared to the indicator response to a reference protein (crystalline amino acid patterned after egg protein). The IAAO method has also been applied to assess the effect of protein complementation directly in humans on the overall protein quality of the diet. The results demonstrate that protein complementation augments the limiting amino acid supply and increases protein synthesis.
    Keywords:  amino acids; indicator amino acid oxidation; metabolic availability; protein quality; slope ratio assay
    DOI:  https://doi.org/10.3389/fnut.2024.1400676
  12. STAR Protoc. 2024 Jun 01. pii: S2666-1667(24)00270-3. [Epub ahead of print]5(2): 103105
    Protocol for separating cancer cell subpopulations by metabolic activity using flow cytometry.
    Wiktoria Blaszczak, Bobby White, Pawel Swietach.
      Cells, even from the same line, can maintain heterogeneity in metabolic activity. Here, we present a protocol, adapted for fluorescence-activated cell sorting (FACS), that separates resuspended cells according to their metabolic rate. We describe steps for driving lactate efflux, which produces an alkaline transient proportional to fermentative rate. This pH signature, measured using pH-sensitive dyes, identifies cells with the highest metabolic rate. We then describe a fluorimetric assay of oxygen consumption and acid production to confirm the metabolic contrast between subpopulations. For complete details on the use and execution of this protocol, please refer to Blaszczak et al.1.
    Keywords:  Cancer; Flow Cytometry; Metabolism
    DOI:  https://doi.org/10.1016/j.xpro.2024.103105
  13. Front Mol Biosci. 2024 ;11 1399679
    Unraveling metabolic characteristics and clinical implications in gastric cancer through single-cell resolution analysis.
    Wenyue Wang, Conghui Li, Yuting Dai, Qingfa Wu, Weiqiang Yu.
      Background: Gastric cancer is a highly prevalent malignant neoplasm. Metabolic reprogramming is intricately linked to both tumorigenesis and cancer immune evasion. The advent of single-cell RNA sequencing technology provides a novel perspective for evaluating cellular metabolism. This study aims to comprehensively investigate the metabolic pathways of various cell types in tumor and normal samples at high resolution and delve into the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer. Methods: Utilizing single-cell RNA sequencing data from gastric cancer, we constructed metabolic landscape maps for different cell types in tumor and normal samples. Employing unsupervised clustering, we categorized malignant cells in tumor samples into high and low metabolic subclusters and further explored the characteristics of these subclusters. Results: Our research findings indicate that epithelial cells in tumor samples exhibit significantly higher activity in most KEGG metabolic pathways compared to other cell types. Unsupervised clustering, based on the scores of metabolic pathways, classified malignant cells into high and low metabolic subclusters. In the high metabolic subcluster, it demonstrated the potential to induce a stronger immune response, correlating with a relatively favorable prognosis. In the low metabolic subcluster, a subset of cells resembling cancer stem cells (CSCs) was identified, and its prognosis was less favorable. Furthermore, a set of risk genes associated with this subcluster was discovered. Conclusion: This study reveals the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer, offering new perspectives for improving prognosis and treatment strategies.
    Keywords:  gastric cancer; malignant cell; metabolic pathway; prognosis; scRNA-seq
    DOI:  https://doi.org/10.3389/fmolb.2024.1399679
  14. Front Oncol. 2024 ;14 1335401
    A glutamatergic biomarker panel enables differentiating Grade 4 gliomas/astrocytomas from brain metastases.
    Falko Lange, Richard Gade, Anne Einsle, Katrin Porath, Gesine Reichart, Claudia Maletzki, Björn Schneider, Christian Henker, Daniel Dubinski, Michael Linnebacher, Rüdiger Köhling, Thomas M Freiman, Timo Kirschstein.
      Background: The differentiation of high-grade glioma and brain tumors of an extracranial origin is eminent for the decision on subsequent treatment regimens. While in high-grade glioma, a surgical resection of the tumor mass is a fundamental part of current standard regimens, in brain metastasis, the burden of the primary tumor must be considered. However, without a cancer history, the differentiation remains challenging in the imaging. Hence, biopsies are common that may help to identify the tumor origin. An additional tool to support the differentiation may be of great help. For this purpose, we aimed to identify a biomarker panel based on the expression analysis of a small sample of tissue to support the pathological analysis of surgery resection specimens. Given that an aberrant glutamate signaling was identified to drive glioblastoma progression, we focused on glutamate receptors and key players of glutamate homeostasis.Methods: Based on surgically resected samples from 55 brain tumors, the expression of ionotropic and metabotropic glutamate receptors and key players of glutamate homeostasis were analyzed by RT-PCR. Subsequently, a receiver operating characteristic (ROC) analysis was performed to identify genes whose expression levels may be associated with either glioblastoma or brain metastasis.
    Results: Out of a total of 29 glutamatergic genes analyzed, nine genes presented a significantly different expression level between high-grade gliomas and brain metastases. Of those, seven were identified as potential biomarker candidates including genes encoding for AMPA receptors GRIA1, GRIA2, kainate receptors GRIK1 and GRIK4, metabotropic receptor GRM3, transaminase BCAT1 and the glutamine synthetase (encoded by GLUL). Overall, the biomarker panel achieved an accuracy of 88% (95% CI: 87.1, 90.8) in predicting the tumor entity. Gene expression data, however, could not discriminate between patients with seizures from those without.
    Conclusion: We have identified a panel of seven genes whose expression may serve as a biomarker panel to discriminate glioblastomas and brain metastases at the molecular level. After further validation, our biomarker signatures could be of great use in the decision making on subsequent treatment regimens after diagnosis.
    Keywords:  biomarker; brain metastasis; epilepsy; glioblastoma; glutamate; glutamate receptors
    DOI:  https://doi.org/10.3389/fonc.2024.1335401
  15. Int J Oncol. 2024 Jul;pii: 72. [Epub ahead of print]65(1):
    Glutathione‑degrading enzymes in the complex landscape of tumors (Review).
    Tianyi Zhang, Chongjie Yao, Xu Zhou, Shimin Liu, Li Qi, Shiguo Zhu, Chen Zhao, Dan Hu, Weidong Shen.
      Glutathione (GSH)‑degrading enzymes are essential for starting the first stages of GSH degradation. These enzymes include extracellular γ‑glutamyl transpeptidase (GGT) and intracellular GSH‑specific γ‑glutamylcyclotransferase 1 (ChaC1) and 2. These enzymes are essential for cellular activities, such as immune response, differentiation, proliferation, homeostasis regulation and programmed cell death. Tumor tissue frequently exhibits abnormal expression of GSH‑degrading enzymes, which has a key impact on the development and spread of malignancies. The present review summarizes gene and protein structure, catalytic activity and regulation of GSH‑degrading enzymes, their vital roles in tumor development (including regulation of oxidative and endoplasmic reticulum stress, control of programmed cell death, promotion of inflammation and tumorigenesis and modulation of drug resistance in tumor cells) and potential role as diagnostic biomarkers and therapeutic targets.
    Keywords:  ChaC1; GGT; GSH degrading enzyme; tumor
    DOI:  https://doi.org/10.3892/ijo.2024.5660
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