CIDeRplusGeneral Information:
| Id: | 6,432 |
| Diseases: |
Cancer
Diabetes mellitus, type II - [OMIM] Insulin resistance |
| Mammalia | |
| review | |
| Reference: | Szeliga M and Obara-Michlewska M(2009) Glutamine in neoplastic cells: focus on the expression and roles of glutaminases Neurochem. Int. 55: 71-75 [PMID: 19428809] |
Interaction Information:
| Comment | Glutamine (Gln) is engaged in synthesis of peptides, nucleotides and amino sugars. Moreover, it is a precursor of Glu, which is metabolized to such molecules as gamma-aminobutyrate, GSH, folic acid. |
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Formal Description Interaction-ID: 60650 |
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| Comment | Glutamine (Gln) is engaged in synthesis of peptides, nucleotides and amino sugars. Moreover, it is a precursor of Glu, which is metabolized to such molecules as gamma-aminobutyrate, GSH, folic acid. |
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Formal Description Interaction-ID: 61077 |
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| Comment | Glutamine (Gln) is engaged in synthesis of peptides, nucleotides and amino sugars. Moreover, it is a precursor of Glu, which is metabolized to such molecules as gamma-aminobutyrate, GSH, folic acid. |
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Formal Description Interaction-ID: 61078 |
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| Comment | Glutamine (Gln) is engaged in synthesis of peptides, nucleotides and amino sugars. Moreover, it is a precursor of Glu, which is metabolized to such molecules as gamma-aminobutyrate, GSH, folic acid. |
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Formal Description Interaction-ID: 61079 |
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| Comment | Glutamine (Gln) is engaged in synthesis of peptides, nucleotides and amino sugars. Moreover, it is a precursor of Glu, which is metabolized to such molecules as gamma-aminobutyrate, GSH, folic acid. |
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Formal Description Interaction-ID: 61080 |
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| Comment | Glutamine (Gln) is engaged in synthesis of peptides, nucleotides and amino sugars. Moreover, it is a precursor of Glu, which is metabolized to such molecules as gamma-aminobutyrate, GSH, folic acid. |
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Formal Description Interaction-ID: 61082 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Glutamine (Gln) is engaged in synthesis of peptides, nucleotides and amino sugars. Moreover, it is a precursor of Glu, which is metabolized to such molecules as gamma-aminobutyrate, GSH, folic acid. |
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Formal Description Interaction-ID: 61083 |
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| Comment | Imbalance between Gln anabolism and catabolism in favor of the latter is a feature of tumors of different origin. Increased activity of glutaminase, highest during exponential phase of cell growth, has been reported for many neoplasms. Concomitantly to higher GA activity, an inhibition of glutamine synthetase (GS, EC 6.3.1.2) has been observed. GS catalyses condensation of glutamate and ammonia to form glutamine, therefore glutamine consumption may exceed its synthesis. Accordingly, low intratumor concentration of Gln has been detected in rapidly growing hepatomas. |
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Formal Description Interaction-ID: 61084 |
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| Drugbank entries | Show/Hide entries for GLUL |
| Comment | Imbalance between Gln anabolism and catabolism in favor of the latter is a feature of tumors of different origin. Increased activity of glutaminase, highest during exponential phase of cell growth, has been reported for many neoplasms. Concomitantly to higher GA activity, an inhibition of glutamine synthetase (GS, EC 6.3.1.2) has been observed. GS catalyses condensation of glutamate and ammonia to form glutamine, therefore glutamine consumption may exceed its synthesis. Accordingly, low intratumor concentration of Gln has been detected in rapidly growing hepatomas. |
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Formal Description Interaction-ID: 61085 |
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| Drugbank entries | Show/Hide entries for GLUL |
| Comment | Imbalance between Gln anabolism and catabolism in favor of the latter is a feature of tumors of different origin. Increased activity of glutaminase, highest during exponential phase of cell growth, has been reported for many neoplasms. Concomitantly to higher GA activity, an inhibition of glutamine synthetase (GS, EC 6.3.1.2) has been observed. GS catalyses condensation of glutamate and ammonia to form glutamine, therefore glutamine consumption may exceed its synthesis. Accordingly, low intratumor concentration of Gln has been detected in rapidly growing hepatomas. |
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Formal Description Interaction-ID: 61086 |
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| Drugbank entries | Show/Hide entries for GLUL |
| Comment | Imbalance between Gln anabolism and catabolism in favor of the latter is a feature of tumors of different origin. Increased activity of glutaminase, highest during exponential phase of cell growth, has been reported for many neoplasms. Concomitantly to higher GA activity, an inhibition of glutamine synthetase (GS, EC 6.3.1.2) has been observed. GS catalyses condensation of glutamate and ammonia to form glutamine, therefore glutamine consumption may exceed its synthesis. Accordingly, low intratumor concentration of Gln has been detected in rapidly growing hepatomas. |
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Formal Description Interaction-ID: 61087 |
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| Drugbank entries | Show/Hide entries for GLUL |
| Comment | Tumors, termed as ‚Äėglutamine traps‚Äô, are able to prevent depletion of Gln by competing with normal cells for its uptake and by augmenting Gln concentration in host tissues. Transport of Gln mediated by membrane transporters is intensified in malignant cells. Overexpression of Gln transporter ASCT2, member of sodium-dependent system ASC family of transporters, has been reported for gliomas, colorectal carcinoma, hepatoma cells and neuroblastoma. Increased level of ASCT2 protein and induced activity of its promoter were observed in human hepatoma HepG2 cells, cultured in presence of elevated concentration of Gln. Glutamine deprivation resulted in opposite effect - a decrease of ASCT2 expression and promoter activity. Those results suggest that transcriptional regulation of ASCT2 expression is mediated by its substrate, glutamine. |
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Formal Description Interaction-ID: 61088 |
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| Drugbank entries | Show/Hide entries for SLC1A5 |
| Comment | Tumors, termed as ‚Äėglutamine traps‚Äô, are able to prevent depletion of Gln by competing with normal cells for its uptake and by augmenting Gln concentration in host tissues. Transport of Gln mediated by membrane transporters is intensified in malignant cells. Overexpression of Gln transporter ASCT2, member of sodium-dependent system ASC family of transporters, has been reported for gliomas, colorectal carcinoma, hepatoma cells and neuroblastoma. Increased level of ASCT2 protein and induced activity of its promoter were observed in human hepatoma HepG2 cells, cultured in presence of elevated concentration of Gln. Glutamine deprivation resulted in opposite effect - a decrease of ASCT2 expression and promoter activity. Those results suggest that transcriptional regulation of ASCT2 expression is mediated by its substrate, glutamine. |
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Formal Description Interaction-ID: 61089 |
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| Drugbank entries | Show/Hide entries for SLC1A5 |
| Comment | When the tumor progresses, depletion of Gln in blood occurs eventually, as a consequence of antineoplastic therapies and high glutaminolytic activity of tumor cells. Hyperammonemia accompanies this condition, probably as a consequence of increased glutaminase activity. |
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Formal Description Interaction-ID: 61090 |
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| Comment | When the tumor progresses, depletion of Gln in blood occurs eventually, as a consequence of antineoplastic therapies and high glutaminolytic activity of tumor cells. Hyperammonemia accompanies this condition, probably as a consequence of increased glutaminase activity. |
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Formal Description Interaction-ID: 61091 |
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| Comment | When the tumor progresses, depletion of Gln in blood occurs eventually, as a consequence of antineoplastic therapies and high glutaminolytic activity of tumor cells. Hyperammonemia accompanies this condition, probably as a consequence of increased glutaminase activity. |
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Formal Description Interaction-ID: 61092 |
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| Comment | Gln catabolism, leading to Glu formation, plays specific role in neoplastic phenotype. High extracellular concentration of Glu favors proliferation and migration of glioma cells, but also adenocarcinoma and breast and lung carcinoma cells. |
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Formal Description Interaction-ID: 61093 |
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| Comment | Glutathione (GSH) is an important product of Gln metabolism. It is a factor responsible for resistance of many tumors for chemo- and radiotherapy. Reducing of GSH levels resulted in decreased number of metastatic loci in mice livers inoculated with B16 melanoma cells. GSH depletion, resulting from Gln deprivation, decreased proliferation and enhanced chemosensitivity of neuroblastoma cells. On the other hand, introducing glutamine into diet may improve anticancer therapy, as was shown for rats bearing DMBA-induced mammary tumors. In these mice, glutaminase and enzymes involved in GSH metabolism were induced in the host and downregulated in tumor cells. |
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Formal Description Interaction-ID: 61094 |
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| Drugbank entries | Show/Hide entries for Glutathione |
| Comment | In mammals, there are two genes coding for GA isoforms: Gls2 and Gls. Comparison of nucleotide sequences of these genes and sequences of the encoded proteins suggests that they arose from gene duplication followed by divergent evolution. GA isoforms exhibit different structural and kinetic properties as well as tissue-specific expression profiles. The Gls2 gene encodes liver-type glutaminase (LGA) that is activated by low concentration of phosphate and is not inhibited by glutamate. Its expression has been identified in liver, brain, pancreas and breast carcinoma cells. The Gls gene encodes kidney-type glutaminase (KGA) that is activated by high phosphate levels, inhibited by glutamate and expressed in all the tissues except liver, particularly strongly in kidney and brain. The GAC isoform, an alternatively spliced variant of KGA is expressed in heart, pancreas, kidneys, lungs and in breast cancer cells. |
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Formal Description Interaction-ID: 61095 |
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| Drugbank entries | Show/Hide entries for GLS2 |
| Comment | In mammals, there are two genes coding for GA isoforms: Gls2 and Gls. Comparison of nucleotide sequences of these genes and sequences of the encoded proteins suggests that they arose from gene duplication followed by divergent evolution. GA isoforms exhibit different structural and kinetic properties as well as tissue-specific expression profiles. The Gls2 gene encodes liver-type glutaminase (LGA) that is activated by low concentration of phosphate and is not inhibited by glutamate. Its expression has been identified in liver, brain, pancreas and breast carcinoma cells. The Gls gene encodes kidney-type glutaminase (KGA) that is activated by high phosphate levels, inhibited by glutamate and expressed in all the tissues except liver, particularly strongly in kidney and brain. The GAC isoform, an alternatively spliced variant of KGA is expressed in heart, pancreas, kidneys, lungs and in breast cancer cells. |
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Formal Description Interaction-ID: 61096 |
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| Drugbank entries | Show/Hide entries for GLS2 |
| Comment | In mammals, there are two genes coding for GA isoforms: Gls2 and Gls. Comparison of nucleotide sequences of these genes and sequences of the encoded proteins suggests that they arose from gene duplication followed by divergent evolution. GA isoforms exhibit different structural and kinetic properties as well as tissue-specific expression profiles. The Gls2 gene encodes liver-type glutaminase (LGA) that is activated by low concentration of phosphate and is not inhibited by glutamate. Its expression has been identified in liver, brain, pancreas and breast carcinoma cells. The Gls gene encodes kidney-type glutaminase (KGA) that is activated by high phosphate levels, inhibited by glutamate and expressed in all the tissues except liver, particularly strongly in kidney and brain. The GAC isoform, an alternatively spliced variant of KGA is expressed in heart, pancreas, kidneys, lungs and in breast cancer cells. |
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Formal Description Interaction-ID: 61099 |
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| Drugbank entries | Show/Hide entries for GLS |