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Pathway Description
Carbamoyl Phosphate Synthetase Deficiency
Homo sapiens
Disease Pathway
Created: 2022-12-12
Last Updated: 2023-10-25
Carbamoyl Phosphate Synthetase Deficiency, also called hyperammonemia due to carbamoyl phosphate synthetase 1 deficiency, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the urea cycle caused by a defective CPS1 gene. The CPS1 gene codes for the protein carbamoyl phosphate synthetase I, which plays a role in the urea cycle. This disorder is characterized by a large accumulation of ammonia in the blood. Symptoms of the disorder include unusual movements, seizures, unusual sleeping or coma. Treatment with citrulline or arginine, which maintains a regular rate of protein creation. It is estimated that carbamoyl phosphate synthetase deficiency affects 1 in 800,000 individuals in Japan.
References
Carbamoyl Phosphate Synthetase Deficiency References
Hoshide R, Matsuura T, Haraguchi Y, Endo F, Yoshinaga M, Matsuda I: Carbamyl phosphate synthetase I deficiency. One base substitution in an exon of the CPS I gene causes a 9-basepair deletion due to aberrant splicing. J Clin Invest. 1993 May;91(5):1884-7. doi: 10.1172/JCI116405.
Pubmed: 8486760
McReynolds JW, Crowley B, Mahoney MJ, Rosenberg LE: Autosomal recessive inheritance of human mitochondrial carbamyl phosphate synthetase deficiency. Am J Hum Genet. 1981 May;33(3):345-53.
Pubmed: 7246541
Finckh U, Kohlschutter A, Schafer H, Sperhake K, Colombo JP, Gal A: Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. Hum Mutat. 1998;12(3):206-11. doi: 10.1002/(SICI)1098-1004(1998)12:3<206::AID-HUMU8>3.0.CO;2-E.
Pubmed: 9711878
Craigen WJ. Mouse Models of Human Genetic Disorders. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. eds. The Online Metabolic and Molecular Bases of Inherited Disease New York, NY: McGraw-Hill; 2014. http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62642751.
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.
Sohocki MM, Sullivan LS, Harrison WR, Sodergren EJ, Elder FF, Weinstock G, Tanase S, Daiger SP: Human glutamate pyruvate transaminase (GPT): localization to 8q24.3, cDNA and genomic sequences, and polymorphic sites. Genomics. 1997 Mar 1;40(2):247-52. doi: 10.1006/geno.1996.4604.
Pubmed: 9119391
Ishiguro M, Takio K, Suzuki M, Oyama R, Matsuzawa T, Titani K: Complete amino acid sequence of human liver cytosolic alanine aminotransferase (GPT) determined by a combination of conventional and mass spectral methods. Biochemistry. 1991 Oct 29;30(43):10451-7. doi: 10.1021/bi00107a013.
Pubmed: 1931970
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
Gomez-Fabre PM, Aledo JC, Del Castillo-Olivares A, Alonso FJ, Nunez De Castro I, Campos JA, Marquez J: Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminase. Biochem J. 2000 Jan 15;345 Pt 2:365-75.
Pubmed: 10620514
Perez-Gomez C, Mates JM, Gomez-Fabre PM, del Castillo-Olivares A, Alonso FJ, Marquez J: Genomic organization and transcriptional analysis of the human l-glutaminase gene. Biochem J. 2003 Mar 15;370(Pt 3):771-84. doi: 10.1042/BJ20021445.
Pubmed: 12444921
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Nakatani Y, Banner C, von Herrath M, Schneider ME, Smith HH, Freese E: Comparison of human brain and liver glutamate dehydrogenase cDNAS. Biochem Biophys Res Commun. 1987 Dec 16;149(2):405-10. doi: 10.1016/0006-291x(87)90381-0.
Pubmed: 3426581
Amuro N, Yamaura M, Goto Y, Okazaki T: Molecular cloning and nucleotide sequence of the cDNA for human liver glutamate dehydrogenase precursor. Biochem Biophys Res Commun. 1988 May 16;152(3):1395-400. doi: 10.1016/s0006-291x(88)80440-6.
Pubmed: 3377777
Nakatani Y, Schneider M, Banner C, Freese E: Complete nucleotide sequence of human glutamate dehydrogenase cDNA. Nucleic Acids Res. 1988 Jul 11;16(13):6237. doi: 10.1093/nar/16.13.6237.
Pubmed: 3399399
Funghini S, Donati MA, Pasquini E, Zammarchi E, Morrone A: Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesions. Hum Mutat. 2003 Oct;22(4):340-1. doi: 10.1002/humu.9184.
Pubmed: 12955727
Aoshima T, Kajita M, Sekido Y, Kikuchi S, Yasuda I, Saheki T, Watanabe K, Shimokata K, Niwa T: Novel mutations (H337R and 238-362del) in the CPS1 gene cause carbamoyl phosphate synthetase I deficiency. Hum Hered. 2001;52(2):99-101. doi: 10.1159/000053360.
Pubmed: 11474210
Pol S, Bousquet-Lemercier B, Pave-Preux M, Pawlak A, Nalpas B, Berthelot P, Hanoune J, Barouki R: Nucleotide sequence and tissue distribution of the human mitochondrial aspartate aminotransferase mRNA. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1309-15. doi: 10.1016/s0006-291x(88)81017-9.
Pubmed: 3207426
Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. doi: 10.1038/nature03187.
Pubmed: 15616553
Horwich AL, Fenton WA, Williams KR, Kalousek F, Kraus JP, Doolittle RF, Konigsberg W, Rosenberg LE: Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase. Science. 1984 Jun 8;224(4653):1068-74. doi: 10.1126/science.6372096.
Pubmed: 6372096
Hata A, Tsuzuki T, Shimada K, Takiguchi M, Mori M, Matsuda I: Structure of the human ornithine transcarbamylase gene. J Biochem. 1988 Feb;103(2):302-8. doi: 10.1093/oxfordjournals.jbchem.a122265.
Pubmed: 2836378
Haraguchi Y, Takiguchi M, Amaya Y, Kawamoto S, Matsuda I, Mori M: Molecular cloning and nucleotide sequence of cDNA for human liver arginase. Proc Natl Acad Sci U S A. 1987 Jan;84(2):412-5. doi: 10.1073/pnas.84.2.412.
Pubmed: 3540966
Takiguchi M, Haraguchi Y, Mori M: Human liver-type arginase gene: structure of the gene and analysis of the promoter region. Nucleic Acids Res. 1988 Sep 26;16(18):8789-802. doi: 10.1093/nar/16.18.8789.
Pubmed: 3174433
Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. doi: 10.1038/nature02055.
Pubmed: 14574404
Matuo S, Tatsuno M, Kobayashi K, Saheki T, Miyata T, Iwanaga S, Amaya Y, Mori M: Isolation of cDNA clones of human argininosuccinate lyase and corrected amino acid sequence. FEBS Lett. 1988 Jul 18;234(2):395-9. doi: 10.1016/0014-5793(88)80124-8.
Pubmed: 3391281
O'Brien WE, McInnes R, Kalumuck K, Adcock M: Cloning and sequence analysis of cDNA for human argininosuccinate lyase. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7211-5. doi: 10.1073/pnas.83.19.7211.
Pubmed: 3463959
Todd S, McGill JR, McCombs JL, Moore CM, Weider I, Naylor SL: cDNA sequence, interspecies comparison, and gene mapping analysis of argininosuccinate lyase. Genomics. 1989 Jan;4(1):53-9.
Pubmed: 2644168
Bock HG, Su TS, O'Brien WE, Beaudet AL: Sequence for human argininosuccinate synthetase cDNA. Nucleic Acids Res. 1983 Sep 24;11(18):6505-12. doi: 10.1093/nar/11.18.6505.
Pubmed: 6194510
Freytag SO, Bock HG, Beaudet AL, O'Brien WE: Molecular structures of human argininosuccinate synthetase pseudogenes. Evolutionary and mechanistic implications. J Biol Chem. 1984 Mar 10;259(5):3160-6.
Pubmed: 6321498
Haberle J, Pauli S, Linnebank M, Kleijer WJ, Bakker HD, Wanders RJ, Harms E, Koch HG: Structure of the human argininosuccinate synthetase gene and an improved system for molecular diagnostics in patients with classical and mild citrullinemia. Hum Genet. 2002 Apr;110(4):327-33. doi: 10.1007/s00439-002-0686-6. Epub 2002 Mar 1.
Pubmed: 11941481
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