α-Ketoglutaramate-A Key Metabolite Contributing to Glutamine Addiction in Cancer Cells

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2022 Nov 21

PMID 36404951

Authors

Arthur J L Cooper

Thambi Dorai

John T Pinto

Travis T Denton

Affiliations

Soon will be listed here.

Citing Articles

Metabolic Heterogeneity, Plasticity, and Adaptation to "Glutamine Addiction" in Cancer Cells: The Role of Glutaminase and the GTωA [Glutamine Transaminase-ω-Amidase (Glutaminase II)] Pathway.

Cooper A, Dorai T, Pinto J, Denton T Biology (Basel). 2023; 12(8).

PMID: 37627015 PMC: 10452834. DOI: 10.3390/biology12081131.

Alone and together: current approaches to targeting glutaminase enzymes as part of anti-cancer therapies.

Nguyen T, Katt W, Cerione R Future Drug Discov. 2023; 4(4):FDD79.

PMID: 37009252 PMC: 10051075. DOI: 10.4155/fdd-2022-0011.

References

Dorai T, Pinto J, Denton T, Krasnikov B, Cooper A . The metabolic importance of the glutaminase II pathway in normal and cancerous cells. Anal Biochem. 2020; 644:114083. DOI: 10.1016/j.ab.2020.114083. View

Hoerner C, Chen V, Fan A . The 'Achilles Heel' of Metabolism in Renal Cell Carcinoma: Glutaminase Inhibition as a Rational Treatment Strategy. Kidney Cancer. 2019; 3(1):15-29. PMC: 6400133. DOI: 10.3233/KCA-180043. View

Meister A, TICE S . Transamination from glutamine to alpha-keto acids. J Biol Chem. 1950; 187(1):173-87. View

Delgir S, Bastami M, Ilkhani K, Safi A, Seif F, Alivand M . The pathways related to glutamine metabolism, glutamine inhibitors and their implication for improving the efficiency of chemotherapy in triple-negative breast cancer. Mutat Res Rev Mutat Res. 2021; 787:108366. DOI: 10.1016/j.mrrev.2021.108366. View

Hersh L . Rat liver omega-amidase. Purification and properties. Biochemistry. 1971; 10(15):2884-91. DOI: 10.1021/bi00791a014. View

Cooper A, Shurubor Y, Dorai T, Pinto J, Isakova E, Deryabina Y . ω-Amidase: an underappreciated, but important enzyme in L-glutamine and L-asparagine metabolism; relevance to sulfur and nitrogen metabolism, tumor biology and hyperammonemic diseases. Amino Acids. 2015; 48(1):1-20. DOI: 10.1007/s00726-015-2061-7. View

Pan T, Gao L, Wu G, Shen G, Xie S, Wen H . Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer. Biochem Biophys Res Commun. 2014; 456(1):452-8. DOI: 10.1016/j.bbrc.2014.11.105. View

Lin C, Chung M, Chen W, Chien C . Growth inhibitory effect of the human NIT2 gene and its allelic imbalance in cancers. FEBS J. 2007; 274(11):2946-56. DOI: 10.1111/j.1742-4658.2007.05828.x. View

Darmaun D, Matthews D, Bier D . Glutamine and glutamate kinetics in humans. Am J Physiol. 1986; 251(1 Pt 1):E117-26. DOI: 10.1152/ajpendo.1986.251.1.E117. View

10.

Li T, Le A . Glutamine Metabolism in Cancer. Adv Exp Med Biol. 2018; 1063:13-32. DOI: 10.1007/978-3-319-77736-8_2. View

11.

Pallett L, Dimeloe S, Sinclair L, Byrne A, Schurich A . A glutamine 'tug-of-war': targets to manipulate glutamine metabolism for cancer immunotherapy. Immunother Adv. 2021; 1(1):ltab010. PMC: 8444990. DOI: 10.1093/immadv/ltab010. View

12.

Koltai T . Targeting the pH Paradigm at the Bedside: A Practical Approach. Int J Mol Sci. 2020; 21(23). PMC: 7730959. DOI: 10.3390/ijms21239221. View

13.

Zhao Y, Feng X, Chen Y, Selfridge J, Gorityala S, Du Z . 5-Fluorouracil Enhances the Antitumor Activity of the Glutaminase Inhibitor CB-839 against -Mutant Colorectal Cancers. Cancer Res. 2020; 80(21):4815-4827. PMC: 7642187. DOI: 10.1158/0008-5472.CAN-20-0600. View

14.

Shurubor Y, Cooper A, Isakova E, Deryabina Y, Beal M, Krasnikov B . HPLC determination of α-ketoglutaramate [5-amino-2,5-dioxopentanoate] in biological samples. Anal Biochem. 2015; 494:52-4. DOI: 10.1016/j.ab.2015.11.003. View

15.

Vergara F, Plum F, Duffy T . Alpha-ketoglutaramate: increased concentrations in the cerebrospinal fluid of patients in hepatic coma. Science. 1974; 183(4120):81-3. DOI: 10.1126/science.183.4120.81. View

16.

Ellens K, Richardson L, Frelin O, Collins J, Ribeiro C, Hsieh Y . Evidence that glutamine transaminase and omega-amidase potentially act in tandem to close the methionine salvage cycle in bacteria and plants. Phytochemistry. 2014; 113:160-9. DOI: 10.1016/j.phytochem.2014.04.012. View

17.

Dorai T, Dorai B, Pinto J, Grasso M, Cooper A . High Levels of Glutaminase II Pathway Enzymes in Normal and Cancerous Prostate Suggest a Role in 'Glutamine Addiction'. Biomolecules. 2019; 10(1). PMC: 7022959. DOI: 10.3390/biom10010002. View

18.

Vanhove K, Derveaux E, Graulus G, Mesotten L, Thomeer M, Noben J . Glutamine Addiction and Therapeutic Strategies in Lung Cancer. Int J Mol Sci. 2019; 20(2). PMC: 6359540. DOI: 10.3390/ijms20020252. View

19.

Kuhara T, Ohse M, Inoue Y, Cooper A . A GC/MS-based metabolomic approach for diagnosing citrin deficiency. Anal Bioanal Chem. 2011; 400(7):1881-94. DOI: 10.1007/s00216-011-4766-0. View

20.

Gatenby R, Gillies R . Why do cancers have high aerobic glycolysis?. Nat Rev Cancer. 2004; 4(11):891-9. DOI: 10.1038/nrc1478. View