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Pathway Description
Phenylketonuria
Homo sapiens
Disease Pathway
Created: 2013-08-01
Last Updated: 2022-11-01
Phenylketonuria, also called Folling disease, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder that affects the proper processing of phenylalanine caused by a defective phenylalanine hydroxylase. Phenylalanine hydroxylase breaks down phenylalanine from the diet. This disorder is characterized by a large accumulation of phenylalanine in the blood and other tissues. Symptoms of the disorder include behavioural problems, psychiatric disorders and seizures. Treatment eating a diet limiting the intake of phenylalanine is very effective. It is estimated that phenylketonuria affects 1 in 15,000 individuals in the United States.
References
Phenylketonuria References
[Uniprot: P00439](http://www.uniprot.org/uniprot/P00439)
[OMIM: Entry 261600](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=261600)
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.80 Heilbronn: SPS Verlagsgesellschaft
Burgard P, Rupp A, Konecki DS, Trefz FK, Schmidt H, Lichter-Konecki U: Phenylalanine hydroxylase genotypes, predicted residual enzyme activity and phenotypic parameters of diagnosis and treatment of phenylketonuria. Eur J Pediatr. 1996 Jul;155 Suppl 1:S11-5.
Pubmed: 8828601
Eisensmith RC, Woo SL: Gene therapy for phenylketonuria. Eur J Pediatr. 1996 Jul;155 Suppl 1:S16-9.
Pubmed: 8828602
Hanley WB, Lee AW, Hanley AJ, Lehotay DC, Austin VJ, Schoonheyt WE, Platt BA, Clarke JT: "Hypotyrosinemia" in phenylketonuria. Mol Genet Metab. 2000 Apr;69(4):286-94. doi: 10.1006/mgme.2000.2985.
Pubmed: 10870846
Kalaydjieva L, Dworniczak B, Kucinskas V, Yurgeliavicius V, Kunert E, Horst J: Geographical distribution gradients of the major PKU mutations and the linked haplotypes. Hum Genet. 1991 Feb;86(4):411-3.
Pubmed: 1671852
Sumaily KM, Mujamammi AH: Phenylketonuria: A new look at an old topic, advances in laboratory diagnosis, and therapeutic strategies. Int J Health Sci (Qassim). 2017 Nov-Dec;11(5):63-70.
Pubmed: 29114196
Phenylalanine and Tyrosine Metabolism References
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Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
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Pubmed: 1974457
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Pubmed: 14702039
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Pubmed: 15164054
Chavan SS, Tian W, Hsueh K, Jawaheer D, Gregersen PK, Chu CC: Characterization of the human homolog of the IL-4 induced gene-1 (Fig1). Biochim Biophys Acta. 2002 Jun 7;1576(1-2):70-80. doi: 10.1016/s0167-4781(02)00295-6.
Pubmed: 12031486
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Pubmed: 16029492
Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. doi: 10.1101/gr.1293003. Epub 2003 Sep 15.
Pubmed: 12975309
Rettenmeier R, Natt E, Zentgraf H, Scherer G: Isolation and characterization of the human tyrosine aminotransferase gene. Nucleic Acids Res. 1990 Jul 11;18(13):3853-61. doi: 10.1093/nar/18.13.3853.
Pubmed: 1973834
Zelenin SM, Mertvetsov NP: [Nucleotide sequence of the human tyrosine aminotransferase gene]. Bioorg Khim. 1994 Feb;20(2):196-204.
Pubmed: 7908801
Seralini GE, Luu-The V, Labrie F: Cloning and expression of human tyrosine aminotransferase cDNA. Biochim Biophys Acta. 1995 Jan 2;1260(1):97-101. doi: 10.1016/0167-4781(94)00191-5.
Pubmed: 7999802
Kwok SC, Ledley FD, DiLella AG, Robson KJ, Woo SL: Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry. 1985 Jan 29;24(3):556-61. doi: 10.1021/bi00324a002.
Pubmed: 2986678
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
Cotton RG, McAdam W, Jennings I, Morgan FJ: A monoclonal antibody to aromatic amino acid hydroxylases. Identification of the epitope. Biochem J. 1988 Oct 1;255(1):193-6. doi: 10.1042/bj2550193.
Pubmed: 2461704
Ribas de Pouplana L, Frugier M, Quinn CL, Schimmel P: Evidence that two present-day components needed for the genetic code appeared after nucleated cells separated from eubacteria. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):166-70. doi: 10.1073/pnas.93.1.166.
Pubmed: 8552597
Kleeman TA, Wei D, Simpson KL, First EA: Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine. J Biol Chem. 1997 May 30;272(22):14420-5. doi: 10.1074/jbc.272.22.14420.
Pubmed: 9162081
Sen S, Zhou H, Ripmaster T, Hittelman WN, Schimmel P, White RA: Expression of a gene encoding a tRNA synthetase-like protein is enhanced in tumorigenic human myeloid leukemia cells and is cell cycle stage- and differentiation-dependent. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6164-9. doi: 10.1073/pnas.94.12.6164.
Pubmed: 9177188
Rodova M, Ankilova V, Safro MG: Human phenylalanyl-tRNA synthetase: cloning, characterization of the deduced amino acid sequences in terms of the structural domains and coordinately regulated expression of the alpha and beta subunits in chronic myeloid leukemia cells. Biochem Biophys Res Commun. 1999 Feb 24;255(3):765-73. doi: 10.1006/bbrc.1999.0141.
Pubmed: 10049785
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