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Pathway Description
Lysinuric Protein Intolerance (LPI)
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
Lysinuric protein intolerance (LPI), also called hyperdibasic aminoaciduria, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the kidney function pathway. It is caused by a mutation in the SLC7A7 gene which encodes the Y+L amino acid transporter 1 protein, which is involved in the uptake of amino acids, both with sodium for neutral amino acids, and without for dibasic amino acids. In this disorder, the amino acids lysin, arginine and ornithine, found in protein, cannot be broken down, which can cause problems in the systems that use these amino acids, such as the urea cycle. LPI is characterized by a shortage of lysine, arginine and ornithine within the body, causing elevated ammonia levels in the blood. Symptoms of the disorder include failure to thrive after weaning, nausea and vomiting following a meal containing large amounts of protein, as well as osteoporosis, and lung and kidney problems. Treatment with a protein restricted diet is effective, as well as prescription of medication to lower the levels of ammonia in the blood. It is estimated that the LPI affects 1 in 60,000 individuals in certain populations such as in Finland and Japan, and less frequently outside these populations.
References
Lysinuric Protein Intolerance (LPI) References
Palacin M, Bertran J, Chillaron J, Estevez R, Zorzano A: Lysinuric protein intolerance: mechanisms of pathophysiology. Mol Genet Metab. 2004 Apr;81 Suppl 1:S27-37. doi: 10.1016/j.ymgme.2003.11.015.
Pubmed: 15050971
Kidney Function References
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Pubmed: 15489334
Ko B, Kamsteeg EJ, Cooke LL, Moddes LN, Deen PM, Hoover RS: RasGRP1 stimulation enhances ubiquitination and endocytosis of the sodium-chloride cotransporter. Am J Physiol Renal Physiol. 2010 Aug;299(2):F300-9. doi: 10.1152/ajprenal.00441.2009. Epub 2010 Apr 14.
Pubmed: 20392800
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
Winters CJ, Zimniak L, Mikhailova MV, Reeves WB, Andreoli TE: Cl(-) channels in basolateral TAL membranes XV. Molecular heterogeneity between cortical and medullary channels. J Membr Biol. 2000 Oct 1;177(3):221-30. doi: 10.1007/s002320010005.
Pubmed: 11014860
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
Ahn YJ, Brooker DR, Kosari F, Harte BJ, Li J, Mackler SA, Kleyman TR: Cloning and functional expression of the mouse epithelial sodium channel. Am J Physiol. 1999 Jul;277(1):F121-9. doi: 10.1152/ajprenal.1999.277.1.F121.
Pubmed: 10409305
Dagenais A, Kothary R, Berthiaume Y: The alpha subunit of the epithelial sodium channel in the mouse: developmental regulation of its expression. Pediatr Res. 1997 Sep;42(3):327-34. doi: 10.1203/00006450-199709000-00013.
Pubmed: 9284273
Harvey KF, Dinudom A, Cook DI, Kumar S: The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. J Biol Chem. 2001 Mar 16;276(11):8597-601. doi: 10.1074/jbc.C000906200. Epub 2001 Jan 17.
Pubmed: 11244092
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
Mukainaka Y, Tanaka K, Hagiwara T, Wada K: Molecular cloning of two glutamate transporter subtypes from mouse brain. Biochim Biophys Acta. 1995 May 11;1244(1):233-7. doi: 10.1016/0304-4165(95)00062-g.
Pubmed: 7766664
Peghini P, Janzen J, Stoffel W: Glutamate transporter EAAC-1-deficient mice develop dicarboxylic aminoaciduria and behavioral abnormalities but no neurodegeneration. EMBO J. 1997 Jul 1;16(13):3822-32. doi: 10.1093/emboj/16.13.3822.
Pubmed: 9233792
Rossier G, Meier C, Bauch C, Summa V, Sordat B, Verrey F, Kuhn LC: LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine. J Biol Chem. 1999 Dec 3;274(49):34948-54. doi: 10.1074/jbc.274.49.34948.
Pubmed: 10574970
Bassi MT, Sperandeo MP, Incerti B, Bulfone A, Pepe A, Surace EM, Gattuso C, De Grandi A, Buoninconti A, Riboni M, Manzoni M, Andria G, Ballabio A, Borsani G, Sebastio G: SLC7A8, a gene mapping within the lysinuric protein intolerance critical region, encodes a new member of the glycoprotein-associated amino acid transporter family. Genomics. 1999 Dec 1;62(2):297-303. doi: 10.1006/geno.1999.5978.
Pubmed: 10610726
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 SMP0000585
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