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Anti-Cancer Agents from Natural Sources
Published in Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg, Promising Drug Molecules of Natural Origin, 2020
Debasish Bandyopadhyay, Felipe Gonzalez
L-glutaminase is another vital enzyme that is primarily produced by bacillus and pseudomonas sp., while also be found in some fungi (Bind et al., 2017). It is extensively used in food industries, but recent research has determined that L-glutaminase has the potential to be a very powerful anti-cancer enzyme. The amino acid L-glutamine is essential for cellular function, especially for protein biosynthesis. The enzyme works by starving cancer cells through a conversion of L-glutamine to glutamic acid and ammonia. This catalytic reaction induced apoptosis because cancerous cells lack the glutamine biosynthesis enzyme, L-glutamine synthase (Unissa et al., 2015). A study conducted in 1966 by El-Asmar et al. (1966) revealed that normal cells were not affected by L-glutaminase because of the transformation of L-glutamine into glutamic acid. A study (Wise et al., 2010) determined that cancerous cells have an addiction to glutamine, as an important mitochondrial substrate, it takes part in NADPH production. For instance, pancreatic carcinoma MIA PaCa-2 and PANC-1 cells, showed dependence on L-glutamine in a study conducted in 1978 (Wu et al., 1978).
Nutritional Ergogenic Aids: Introduction, Definitions and Regulatory Issues
Published in Ira Wolinsky, Judy A. Driskell, Nutritional Ergogenic Aids, 2004
Ira Wolinsky, Judy A. Driskell
Glutamine is degraded to alpha-ketoglutarate, which is an important intermediate in several metabolic pathways, such as the citric acid cycle and the transamination process.1,2 Glutamine can also be converted to glutamate by the enzyme glutaminase, and thus plays an important role in the transami-nation process, synthesis of several key proteins, precursors of other non-essential amino acids and synthesis of excitatory neurotransmitters. Figure 9.2 summarizes the metabolism of glutamine
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
see glutamine glutamine Glutamine is the precursor of the neurotransmitter GLUTAMATE; GLUTAMINASE is the enzyme that catalyses the conversion of glutamine to glutamate (see CATALYST). Curiously, glutamine is synthesized from glutamate, a reaction catalysed by the enzyme GLUTAMINE SYNTHETASE. Why should it be possible to use glutamate to make glutamine, which is then used to make glutamate? The likeliest explanation is that glutamine is stored in NEURONS and glia as an inactive form of glutamate—a reservoir that can be called on if required. It is possible that the conversion of glutamine to glutamate can occur in neurons, though it can certainly occur in astrocytes (see GLIAL CELLS). Astrocytes appear able to transport glutamate across membranes into the neurons they support.
Overcoming cisplatin resistance of human lung cancer by sinomenine through targeting the miR-200a-3p-GLS axis
Published in Journal of Chemotherapy, 2023
Accumulating studies focussed on the re-programming of cancer cells by adapting their nutrient metabolism to meet the high demand for proliferation and maintaining tumour environment balance [18]. Glutamine is a known amino acid which is utilized by cancer cells for proliferation as well as survival under chemotherapeutic agent treatment [19]. To investigate the cellular processes which might be targeted by sinomenine, we examined the effects of sinomenine on the glutamine metabolism of lung cancer cells. A549 cells were exposed to increased concentrations of sinomenine for 48 h. Results from Figure 2A demonstrated that the overall glutamine consumption was significantly suppressed by sinomenine treatments. Meanwhile, the glutaminase activity was remarkedly inhibited by sinomenine treatments (Figure 2B). To evaluate the biological roles of glutamine metabolism in the sinomenine-induced lung cancer cell death, A549 cells were cultured with full medium or low glutamine medium for 24 h. Cells were then treated with sinomenine at the indicated concentrations. Expectedly, A549 cells with low glutamine supply showed a more adaptive phenotype than cells cultured with normal glutamine by MTT assay and clonogenic assay (Figure 2C,D), suggesting cells with low glutamine metabolism were less sensitive to glutamine metabolism. Taken together, these results clearly demonstrated sinomenine could target glutamine metabolism of lung cancer cells.
New insights into the metabolism of Th17 cells
Published in Immunological Medicine, 2023
Besides glycolysis, glutaminolysis also has a vital role in energy production in proliferating cells, including T cells [13]. Th17 cells depend more on glycolysis than other T cell subsets [74]. SLC1A5, known as alanine-serine-cysteine transporter 2 (ASCT2), transports neutral amino acids, including glutamine [75]. Deletion of Slc1a5 leads to impaired Th1 and Th17 cell differentiation [75]. Glutaminase is the first enzyme involved in glutaminolysis, converting glutamine to glutamate. ICER also binds to the promoter region of glutaminase 1 and enhances its expression (Figure 1) [74]. The glutaminase 1 inhibitor, Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), reduces Th17 cell differentiation and disease activity of MRL/lpr mice and EAE models [74,76]. Glutaminase 2 is another isoenzyme of glutaminase. Glutaminase 2 expression is reduced in CD4 T cells from MRL/lpr and patients with SLE [77]. Glutaminase 2 reduces ROS levels in T cells and promotes IL-2 production, which is reduced in lupus T cells [77]. Glutamate oxaloacetate transaminase 1 (GOT1) converts glutamate to α-ketoglutarate. Inhibition of GOT1 with aminooxy acetic acid (AOA) treatment or short hairpin RNA (shRNA) knockdown decreases Th17 differentiation of murine T cells [78] AOA treatment or adoptive transfer of Got1 knockdown Th17-polarized T cells ameliorates EAE [78].
An expert overview of emerging therapies for acute myeloid leukemia: novel small molecules targeting apoptosis, p53, transcriptional regulation and metabolism
Published in Expert Opinion on Investigational Drugs, 2020
Kapil Saxena, Marina Konopleva
Glutamine metabolism is involved in hematopoietic cell survival primarily via an indirect role in ATP production [116]. Glutamine is converted to glutamate via the enzyme glutaminase (GLS) [116]. The mitochondrial enzyme glutamate dehydrogenase 1 (GLUD1, encoded by the gene GLUD1) subsequently converts glutamate to alpha-ketoglutarate, a substrate in the citric acid (TCA) cycle [116]. There are two major isoenzymes of GLS: GLS1 (encoded by the gene GLS) and GLS2 (encoded by the gene GLS2) [117]. The Cancer Genome Atlas shows that GLS and GLUD1 are overexpressed in AML cells [116]. Furthermore, the GLS1 isoforms kidney-type glutaminase (KGA) and glutaminase C (GAC) are present at the protein level in both AML cell lines and primary samples [116,118]. AML cells have an increased number of mitochondria and a higher oxygen consumption rate (OCR) compared to normal hematopoietic cells, not unexpected given their high replicative capacity [116]. Removal of glutamine from the cell culture medium of AML cells leads to a reduction in oxidative phosphorylation (OxPhos), which leads to decreased ATP production and resultant apoptosis [116,118]. Furthermore, GLS1 knockdown leads to increased apoptosis of AML cell lines but not of nontransformed CD34+ hematopoietic cells [118]. Thus, as with other cancer cell types, AML cells seem to require high levels of glutamine for sufficient energy production and survival.