Loading Pathway...
Error: Pathway image not found.
Hide
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, vulvular heart disease, black or brown urine, black and brown eyes, ears, and skin, and urolithiasis. Treatment includes a low-protein diet with vitamin C.
References
Alkaptonuria References
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. doi: 10.1086/301805.
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, Perry M, Chen M: 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
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.
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
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings