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Pathway Description
Alkaptonuria
Homo sapiens
Disease Pathway
Alkaptonuria (Homogentisic acid oxidase deficiency) is an autosomal recessive disease caused by a mutation in the HGD gene which codes for homogentisate 1,2-dioxygenase. A mutation in this enzyme results in accumulation of homogentisic acid in urine. Symptoms, which present in adulthood, include arthritis, black or brown urine, and urolithiasis. Treatment includes a low-protein diet with vitamin C.
References
Alkaptonuria References
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.22 Heilbronn: SPS Verlagsgesellschaft
[Uniprot: Q93099](http://www.uniprot.org/uniprot/Q93099)
[OMIM: Entry 203500](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=203500)
[Wikipedia: Alkaptonuria](http://en.wikipedia.org/wiki/Alkaptonuria)
Alcaptonuria.In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S. The Metabolic Basis of Inherited Disease. New York: McGraw-Hill (pp. 268-282) (4th ed.) 1978.
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.24 Heilbronn: SPS Verlagsgesellschaft
Beltran-Valero de Bernabe D, Granadino B, Chiarelli I, Porfirio B, Mayatepek E, Aquaron R, Moore MM, Festen JJ, Sanmarti R, Penalva MA, de Cordoba SR: Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients. Am J Hum Genet. 1998 Apr;62(4):776-84.
Pubmed: 9529363
Elcioglu NH, Aytug AF, Muller CR, Gurbuz O, Ergun T, Kotiloglu E, Elcioglu M: Alkaptonuria caused by compound heterozygote mutations. Genet Couns. 2003;14(2):207-13.
Pubmed: 12872815
Fernandez-Canon JM, Granadino B, Beltran-Valero de Bernabe D, Renedo M, Fernandez-Ruiz E, Penalva MA, Rodriguez de Cordoba S: The molecular basis of alkaptonuria. Nat Genet. 1996 Sep;14(1):19-24. doi: 10.1038/ng0996-19.
Pubmed: 8782815
Gehrig A, Schmidt SR, Muller CR, Srsen S, Srsnova K, Kress W: Molecular defects in alkaptonuria. Cytogenet Cell Genet. 1997;76(1-2):14-6. doi: 10.1159/000134501.
Pubmed: 9154114
Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, Anderson PD, Huizing M, Anikster Y, Gerber LH, Gahl WA: Natural history of alkaptonuria. N Engl J Med. 2002 Dec 26;347(26):2111-21. doi: 10.1056/NEJMoa021736.
Pubmed: 12501223
Introne WJ, Gahl WA: Alkaptonuria
Pubmed: 20301627
Preston AJ, Keenan CM, Sutherland H, Wilson PJ, Wlodarski B, Taylor AM, Williams DP, Ranganath LR, Gallagher JA, Jarvis JC: Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone. Ann Rheum Dis. 2014 Jan;73(1):284-9. doi: 10.1136/annrheumdis-2012-202878. Epub 2013 Mar 19.
Pubmed: 23511227
Tyrosine Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.)Â (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Yang YS, Wang CC, Chen BH, Hou YH, Hung KS, Mao YC: Tyrosine sulfation as a protein post-translational modification. Molecules. 2015 Jan 28;20(2):2138-64. doi: 10.3390/molecules20022138.
Pubmed: 25635379
Lee RW, Huttner WB: Tyrosine-O-sulfated proteins of PC12 pheochromocytoma cells and their sulfation by a tyrosylprotein sulfotransferase. J Biol Chem. 1983 Sep 25;258(18):11326-34.
Pubmed: 6577005
Westmuckett AD, Thacker KM, Moore KL: Tyrosine sulfation of native mouse Psgl-1 is required for optimal leukocyte rolling on P-selectin in vivo. PLoS One. 2011;6(5):e20406. doi: 10.1371/journal.pone.0020406. Epub 2011 May 25.
Pubmed: 21633705
Ruzzene M, Donella-Deana A, Marin O, Perich JW, Ruzza P, Borin G, Calderan A, Pinna LA: Specificity of T-cell protein tyrosine phosphatase toward phosphorylated synthetic peptides. Eur J Biochem. 1993 Jan 15;211(1-2):289-95. doi: 10.1111/j.1432-1033.1993.tb19897.x.
Pubmed: 7678807
Honova E, Miller SA, Ehrenkranz RA, Woo A: Tyrosine transaminase: development of daily rhythm in liver of neonatal rat. Science. 1968 Nov 29;162(3857):999-1001. doi: 10.1126/science.162.3857.999.
Pubmed: 4387001
Bartesaghi S, Valez V, Trujillo M, Peluffo G, Romero N, Zhang H, Kalyanaraman B, Radi R: Mechanistic studies of peroxynitrite-mediated tyrosine nitration in membranes using the hydrophobic probe N-t-BOC-L-tyrosine tert-butyl ester. Biochemistry. 2006 Jun 6;45(22):6813-25. doi: 10.1021/bi060363x.
Pubmed: 16734418
Goldstein S, Czapski G, Lind J, Merenyi G: Tyrosine nitration by simultaneous generation of (.)NO and O-(2) under physiological conditions. How the radicals do the job. J Biol Chem. 2000 Feb 4;275(5):3031-6. doi: 10.1074/jbc.275.5.3031.
Pubmed: 10652282
Radi R: Protein tyrosine nitration: biochemical mechanisms and structural basis of functional effects. Acc Chem Res. 2013 Feb 19;46(2):550-9. doi: 10.1021/ar300234c. Epub 2012 Nov 16.
Pubmed: 23157446
Sherry DM, Kanan Y, Hamilton R, Hoffhines A, Arbogast KL, Fliesler SJ, Naash MI, Moore KL, Al-Ubaidi MR: Differential developmental deficits in retinal function in the absence of either protein tyrosine sulfotransferase-1 or -2. PLoS One. 2012;7(6):e39702. doi: 10.1371/journal.pone.0039702. Epub 2012 Jun 22.
Pubmed: 22745813
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