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Pathway Description
Hyperphenylalaninemia Due to DHPR-Deficiency
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-16
Hyperphenylalaninemia due to dihydropteridine reductase deficiency (DHPR) is the high presence of phenylalanine in the system/blood caused by a genetic mutation. More specificially, mutations in the QDPR gene are the root cause of the condition. One observes that such a mutation results in an error encoding a reductase enzyme, and from there a chain reaction of effects lead to the observed effects of the disease. The mutation is autosomal recessive.
When tetrahydrobiopterin levels drop, the breakdown of many several amino acids, such as phenylalanine, is reduced and as a result their levels in the blood augment.
Symptoms of hyperphenylalaninemia due to dihydropteridine reductase deficiency include: dysphagia, global development delay, microcephaly, and intellectual disability (among others). Treatment consists of BH4 supplements as well as other medical treatments.
References
Hyperphenylalaninemia Due to DHPR-Deficiency References
Arai N, Narisawa K, Hayakawa H, Tada K: Hyperphenylalaninemia due to dihydropteridine reductase deficiency: diagnosis by enzyme assays on dried blood spots. Pediatrics. 1982 Sep;70(3):426-30.
Pubmed: 7110817
Pterine Biosynthesis References
Hatakeyama K, Inoue Y, Harada T, Kagamiyama H: Cloning and sequencing of cDNA encoding rat GTP cyclohydrolase I. The first enzyme of the tetrahydrobiopterin biosynthetic pathway. J Biol Chem. 1991 Jan 15;266(2):765-9.
Pubmed: 1985963
Imazumi K, Sasaki T, Takahashi K, Takai Y: Identification of a rabphilin-3A-interacting protein as GTP cyclohydrolase I in PC12 cells. Biochem Biophys Res Commun. 1994 Dec 15;205(2):1409-16. doi: 10.1006/bbrc.1994.2822.
Pubmed: 7802677
Hatakeyama K, Harada T, Suzuki S, Watanabe Y, Kagamiyama H: Purification and characterization of rat liver GTP cyclohydrolase I. Cooperative binding of GTP to the enzyme. J Biol Chem. 1989 Dec 25;264(36):21660-4.
Pubmed: 2557335
Milstien S, Jaffe H, Kowlessur D, Bonner TI: Purification and cloning of the GTP cyclohydrolase I feedback regulatory protein, GFRP. J Biol Chem. 1996 Aug 16;271(33):19743-51. doi: 10.1074/jbc.271.33.19743.
Pubmed: 8702680
Yoneyama T, Brewer JM, Hatakeyama K: GTP cyclohydrolase I feedback regulatory protein is a pentamer of identical subunits. Purification, cDNA cloning, and bacterial expression. J Biol Chem. 1997 Apr 11;272(15):9690-6. doi: 10.1074/jbc.272.15.9690.
Pubmed: 9092499
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
Inoue Y, Kawasaki Y, Harada T, Hatakeyama K, Kagamiyama H: Purification and cDNA cloning of rat 6-pyruvoyl-tetrahydropterin synthase. J Biol Chem. 1991 Nov 5;266(31):20791-6.
Pubmed: 1939130
Nar H, Huber R, Heizmann CW, Thony B, Burgisser D: Three-dimensional structure of 6-pyruvoyl tetrahydropterin synthase, an enzyme involved in tetrahydrobiopterin biosynthesis. EMBO J. 1994 Mar 15;13(6):1255-62.
Pubmed: 8137809
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 SMP0000489
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