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Pathway Description
Glutaminolysis and Cancer
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-08-31
Last Updated: 2019-08-16
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
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
Johnson MT, Mahmood S, Hyatt SL, Yang HS, Soloway PD, Hanson RW, Patel MS: Inactivation of the murine pyruvate dehydrogenase (Pdha1) gene and its effect on early embryonic development. Mol Genet Metab. 2001 Nov;74(3):293-302. doi: 10.1006/mgme.2001.3249.
Pubmed: 11708858
Fitzgerald J, Hutchison WM, Dahl HH: Isolation and characterisation of the mouse pyruvate dehydrogenase E1 alpha genes. Biochim Biophys Acta. 1992 May 7;1131(1):83-90. doi: 10.1016/0167-4781(92)90102-6.
Pubmed: 1581363
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y: The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. doi: 10.1126/science.1112014.
Pubmed: 16141072
Ballif BA, Carey GR, Sunyaev SR, Gygi SP: Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain. J Proteome Res. 2008 Jan;7(1):311-8. doi: 10.1021/pr0701254. Epub 2007 Nov 23.
Pubmed: 18034455
Wang L, Kaneko S, Kagaya M, Ohno H, Honda M, Kobayashi K: Molecular cloning, and characterization and expression of dihydrolipoamide acetyltransferase component of murine pyruvate dehydrogenase complex in bile duct cancer cells. J Gastroenterol. 2002;37(6):449-54. doi: 10.1007/s005350200065.
Pubmed: 12108679
Johnson M, Yang HS, Johanning GL, Patel MS: Characterization of the mouse dihydrolipoamide dehydrogenase (Dld) gene: genomic structure, promoter sequence, and chromosomal localization. Genomics. 1997 May 1;41(3):320-6. doi: 10.1006/geno.1997.4670.
Pubmed: 9169128
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
Pubmed: 21183079
Brenner V, Nyakatura G, Rosenthal A, Platzer M: Genomic organization of two novel genes on human Xq28: compact head to head arrangement of IDH gamma and TRAP delta is conserved in rat and mouse. Genomics. 1997 Aug 15;44(1):8-14. doi: 10.1006/geno.1997.4822.
Pubmed: 9286695
Trinidad JC, Specht CG, Thalhammer A, Schoepfer R, Burlingame AL: Comprehensive identification of phosphorylation sites in postsynaptic density preparations. Mol Cell Proteomics. 2006 May;5(5):914-22. doi: 10.1074/mcp.T500041-MCP200. Epub 2006 Feb 1.
Pubmed: 16452087
Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP: Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5;7(5):e1000112. doi: 10.1371/journal.pbio.1000112. Epub 2009 May 26.
Pubmed: 19468303
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0002298
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