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Pathway Description
Glutaminolysis and Cancer
Homo sapiens
Disease Pathway
The glutaminolysis pathway catabolizes glutamine to generate ATP and lactate. Glutamine not only provides a major substrate for respiration but also for the synthesis of other macromolecules, such as nucleotides, proteins and hexosamines. It also macromolecule biosynthesis, glutaminolysis also has an important role in regulating redox balance, mTOR signaling, apoptosis and autophagy.
High extracellular glutamine concentrations stimulate tumor growth and are essential for cell transformation. The transportation of glutamine in and out regulates mTOR activation to coordinate cell growth and proliferation.
Glutaminolysis is a series of biochemical reactions by which glutamine is degraded into glutamate, aspartate, CO2, pyruvate, lactate, alanine and citrate.
Glutamine is imported through ASCT2 and SN2, once inside the cell, it can be deaminated into glutamate. Glutamate is converted into Oxoglutaric acid which then is incorporated into the TCA cycle. Once it reaches malic acid, it is transported outside the mitochondria and transformed into pyruvic acid and lactate.
The oxoglutaric acid can also be transformed into citric acid which then gets turned into acetyl coa and get incorporated into the lipid synthesis
References
Glutaminolysis and Cancer References
Jin L, Alesi GN, Kang S: Glutaminolysis as a target for cancer therapy. Oncogene. 2016 Jul 14;35(28):3619-25. doi: 10.1038/onc.2015.447. Epub 2015 Nov 23.
Pubmed: 26592449
Chen JQ, Russo J: Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells. Biochim Biophys Acta. 2012 Dec;1826(2):370-84. doi: 10.1016/j.bbcan.2012.06.004. Epub 2012 Jun 27.
Pubmed: 22750268
Yang L, Venneti S, Nagrath D: Glutaminolysis: A Hallmark of Cancer Metabolism. Annu Rev Biomed Eng. 2017 Jun 21;19:163-194. doi: 10.1146/annurev-bioeng-071516-044546. Epub 2017 Mar 8.
Pubmed: 28301735
Shroff EH, Eberlin LS, Dang VM, Gouw AM, Gabay M, Adam SJ, Bellovin DI, Tran PT, Philbrick WM, Garcia-Ocana A, Casey SC, Li Y, Dang CV, Zare RN, Felsher DW: MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6539-44. doi: 10.1073/pnas.1507228112. Epub 2015 May 11.
Pubmed: 25964345
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