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Pathway Description
Glucose-Alanine Cycle
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-01-21
Last Updated: 2019-09-12
The glucose-alanine cycle—also referred to in the literature as the Cahill cycle or the alanine cycle—involves muscle protein being degraded to provide more glucose to generate additional ATP for muscle contraction. It allows pyruvate and glutamate to be transported out of muscle tissue to the liver where gluconeogenesis takes place to supply the muscle tissue with more glucose as mentioned previously.
To initiate the cycle, muscle and tissues that catabolize amino acids for fuel generate amino groups—most commonly in the form of glutamate—through the process of transamination. These amino groups are transferred via alanine aminotransferase to pyruvate (a product of glycolysis) to form alanine and alpha-ketoglutarate.
Alanine subsequently moves through the circulatory system to the liver where the reaction previously catalyzed by alanine aminotransferase is reversed to produce pyruvate. This pyruvate is converted into glucose through the process of gluconeogenesis which subsequently is transported back to the muscle tissue. Meanwhile, glutamate dehydrogenase in the mitochondria catabolizes glutamate into ammonium. Ammonium moves on to form urea in the urea cycle.
References
Glucose-Alanine Cycle References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Jadhao SB, Yang RZ, Lin Q, Hu H, Anania FA, Shuldiner AR, Gong DW: Murine alanine aminotransferase: cDNA cloning, functional expression, and differential gene regulation in mouse fatty liver. Hepatology. 2004 May;39(5):1297-302. doi: 10.1002/hep.20182.
Pubmed: 15122758
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Pubmed: 16141072
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
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
Tzimagiorgis G, Moschonas NK: Molecular cloning, structure and expression analysis of a full-length mouse brain glutamate dehydrogenase cDNA. Biochim Biophys Acta. 1991 Jun 13;1089(2):250-3. doi: 10.1016/0167-4781(91)90017-g.
Pubmed: 1711373
Gu S, Langlais P, Liu F, Jiang JX: Mouse system-N amino acid transporter, mNAT3, expressed in hepatocytes and regulated by insulin-activated and phosphoinositide 3-kinase-dependent signalling. Biochem J. 2003 May 1;371(Pt 3):721-31. doi: 10.1042/BJ20030049.
Pubmed: 12537539
Suzue K, Lodish HF, Thorens B: Sequence of the mouse liver glucose transporter. Nucleic Acids Res. 1989 Dec 11;17(23):10099. doi: 10.1093/nar/17.23.10099.
Pubmed: 2602116
Asano T, Shibasaki Y, Lin JL, Akanuma Y, Takaku F, Oka Y: The nucleotide sequence of cDNA for a mouse liver-type glucose transporter protein. Nucleic Acids Res. 1989 Aug 11;17(15):6386. doi: 10.1093/nar/17.15.6386.
Pubmed: 2771649
Kaestner KH, Christy RJ, McLenithan JC, Braiterman LT, Cornelius P, Pekala PH, Lane MD: Sequence, tissue distribution, and differential expression of mRNA for a putative insulin-responsive glucose transporter in mouse 3T3-L1 adipocytes. Proc Natl Acad Sci U S A. 1989 May;86(9):3150-4. doi: 10.1073/pnas.86.9.3150.
Pubmed: 2654938
Ueda H, Ikegami H, Kawaguchi Y, Fujisawa T, Nojima K, Babaya N, Yamada K, Shibata M, Yamato E, Ogihara T: Age-dependent changes in phenotypes and candidate gene analysis in a polygenic animal model of Type II diabetes mellitus; NSY mouse. Diabetologia. 2000 Jul;43(7):932-8. doi: 10.1007/s001250051472.
Pubmed: 10952468
Trost M, English L, Lemieux S, Courcelles M, Desjardins M, Thibault P: The phagosomal proteome in interferon-gamma-activated macrophages. Immunity. 2009 Jan 16;30(1):143-54. doi: 10.1016/j.immuni.2008.11.006.
Pubmed: 19144319
Gundry RL, Raginski K, Tarasova Y, Tchernyshyov I, Bausch-Fluck D, Elliott ST, Boheler KR, Van Eyk JE, Wollscheid B: The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation. Mol Cell Proteomics. 2009 Nov;8(11):2555-69. doi: 10.1074/mcp.M900195-MCP200. Epub 2009 Aug 4.
Pubmed: 19656770
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 SMP0000127
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