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Pathway Description
Hyperphenylalaninemia Due to Guanosine Triphosphate Cyclohydrolase Deficiency
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-16
Hyperphenylalaninemia is the high presence of phenylalanine in the system/blood caused by a genetic mutation. In this case a missense error in the gene which encodes GTP cyclohydrolase. Consequently, this form of hyperphenylalaninemia is also called GTP cyclohydrolase I deficiency and/or dopa-responsive dystonia. It is an autosomal recessive mutation.
The mutation results in a reduction in the production of BH4 which is a necessary component in the reaction which transforms phenylalanine to other products in the body.
Common symptoms include: abnormality of eye mpvement, choreoathetosis, dysphagia, dystonia, excessive salivation, hypekinesis, lethargy, limb hyptertonia, seizures, tremor, among others.
References
Hyperphenylalaninemia Due to Guanosine Triphosphate Cyclohydrolase Deficiency References
Coskun T, Karagoz T, Kalkanoglu S, Tokatli A, Ozalp I, Thony B, Blau N: Guanosine triphosphate cyclohydrolase I deficiency: a rare cause of hyperphenylalaninemia. Turk J Pediatr. 1999 Apr-Jun;41(2):231-7.
Pubmed: 10770663
Pterine Biosynthesis 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.
Thony B, Auerbach G, Blau N: Tetrahydrobiopterin biosynthesis, regeneration and functions. Biochem J. 2000 Apr 1;347 Pt 1:1-16.
Pubmed: 10727395
Longo N: Disorders of biopterin metabolism. J Inherit Metab Dis. 2009 Jun;32(3):333-42. doi: 10.1007/s10545-009-1067-2. Epub 2009 Feb 9.
Pubmed: 19234759
Nomura T, Ichinose H, Sumi-Ichinose C, Nomura H, Hagino Y, Fujita K, Nagatsu T: Cloning and sequencing of cDNA encoding mouse GTP cyclohydrolase I. Biochem Biophys Res Commun. 1993 Mar 15;191(2):523-7. doi: 10.1006/bbrc.1993.1249.
Pubmed: 8461009
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
Gutlich M, Schott K, Werner T, Bacher A, Ziegler I: Detection and quantification of GTP cyclohydrolase I mRNA. Adv Exp Med Biol. 1993;338:167-70. doi: 10.1007/978-1-4615-2960-6_32.
Pubmed: 8304101
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Pubmed: 16141072
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
Turri MO, Ilg EC, Thony B, Blau N: Structure, genomic localization and recombinant expression of the mouse 6-pyruvoyl-tetrahydropterin synthase gene. Biol Chem. 1998 Dec;379(12):1441-7.
Pubmed: 9894812
Ota A, Ichinose H, Nagatsu T: Mouse sepiapterin reductase: an enzyme involved in the final step of tetrahydrobiopterin biosynthesis. Primary structure deduced from the cDNA sequence. Biochim Biophys Acta. 1995 Feb 21;1260(3):320-2. doi: 10.1016/0167-4781(94)00225-r.
Pubmed: 7873607
Lee SW, Park IY, Hahn Y, Lee JE, Seong CS, Chung JH, Park YS: Cloning of mouse sepiapterin reductase gene and characterization of its promoter region. Biochim Biophys Acta. 1999 Apr 14;1445(1):165-71. doi: 10.1016/s0167-4781(99)00030-5.
Pubmed: 10209270
Maier J, Schott K, Werner T, Bacher A, Ziegler I: Northern blot analysis of sepiapterin reductase mRNA in mammalian cell lines and tissues. Adv Exp Med Biol. 1993;338:195-8. doi: 10.1007/978-1-4615-2960-6_39.
Pubmed: 8304109
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 SMP0000487
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