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Pathway Description
Adenine Phosphoribosyltransferase Deficiency (APRT)
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
Adenine phosphoribosyltransferase deficiency, which is also known as APRTD or APRT deficiency, is a rare inherited inborn error of metabolism (IEM) leading to the recurrent formation of kidney stones. It is an autosomal recessive disorder associated with a mutation in the enzyme adenine phosphoribosyltransferase (APRT). APRT is involved in the nucleotide salvage pathway, which provides an alternative, and energetically more efficient route to nucleotide biosynthesis in humans and most other animals. A defect in this enzyme can lead to the accumulation of the insoluble purine known as 2,8-dihydroxyadenine. In particular, when APRT has reduced or nonexistent activity, adenine accumulates which is then degraded by xanthine dehydrogenase to 2,8-dihydroxyadenine (DHA). 2,8-Dihydroxyadenine is a derivative of adenine which accumulates in 2,8 dihydroxyadenine urolithiasis (kidney stones). Kidney and urinary tract stones can obstruct the urinary tract, resulting in pain and difficulty urinating. If left untreated, the condition can eventually produce kidney failure. APRTD was first diagnosed in 1976. There are two categories of APRTD: type I involves a complete loss of the APRT function while type II involves a partial loss and is mostly found in Japan. APRT deficiency is estimated to affect 1 in 27 000 people in Japan. APRTD is rarer in Europe, where it affects 1 in 50 000 to 100 000 people. A diagnosis of APRTD can be made by analyzing kidney stones or measuring DHA concentrations in urine. APRTD is treatable with regular doses of allopurinol, which inhibits xanthine dehydrogenase activity. APRTD can also be treated with a low-purine diet and a high fluid intake.
References
Adenine Phosphoribosyltransferase Deficiency (APRT) References
Bollee G, Harambat J, Bensman A, Knebelmann B, Daudon M, Ceballos-Picot I: Adenine phosphoribosyltransferase deficiency. Clin J Am Soc Nephrol. 2012 Sep;7(9):1521-7. doi: 10.2215/CJN.02320312. Epub 2012 Jun 14.
Pubmed: 22700886
Engle SJ, Stockelman MG, Chen J, Boivin G, Yum MN, Davies PM, Ying MY, Sahota A, Simmonds HA, Stambrook PJ, Tischfield JA: Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5307-12.
Pubmed: 8643571
Purine Metabolism References
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
Mehus JG, Deloukas P, Lambeth DO: NME6: a new member of the nm23/nucleoside diphosphate kinase gene family located on human chromosome 3p21.3. Hum Genet. 1999 Jun;104(6):454-9. doi: 10.1007/s004390050987.
Pubmed: 10453732
Fausther M, Lecka J, Kukulski F, Levesque SA, Pelletier J, Zimmermann H, Dranoff JA, Sevigny J: Cloning, purification, and identification of the liver canalicular ecto-ATPase as NTPDase8. Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G785-95. doi: 10.1152/ajpgi.00293.2006. Epub 2006 Nov 9.
Pubmed: 17095758
Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.
Pubmed: 15632090
Ahmed F, Torrado M, Zinovieva RD, Senatorov VV, Wistow G, Tomarev SI: Gene expression profile of the rat eye iridocorneal angle: NEIBank expressed sequence tag analysis. Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3081-90. doi: 10.1167/iovs.04-0302.
Pubmed: 15326124
Stegmann AP, Honders MW, Willemze R, Landegent JE: Cloning of the Dck gene encoding rat deoxycytidine kinase. Gene. 1994 Dec 15;150(2):351-4. doi: 10.1016/0378-1119(94)90451-0.
Pubmed: 7821805
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Fieldhouse D, Golding GB: The rat adenine phosphoribosyltransferase sequence shows evolutionary rate variation among exons in rodents. Genome. 1993 Dec;36(6):1107-10.
Pubmed: 8112572
Maurya DK, Sundaram CS, Bhargava P: Proteome profile of the mature rat olfactory bulb. Proteomics. 2009 May;9(9):2593-9. doi: 10.1002/pmic.200800664.
Pubmed: 19343716
Chiaverotti TA, Battula N, Monnat RJ Jr: Rat hypoxanthine phosphoribosyltransferase cDNA cloning and sequence analysis. Genomics. 1991 Dec;11(4):1158-60.
Pubmed: 1783384
Chiaverotti TA, Battula N, Monnat RJ Jr: Rat hypoxanthine phosphoribosyltransferase cDNA cloning and sequence analysis. Adv Exp Med Biol. 1991;309B:117-20. doi: 10.1007/978-1-4615-7703-4_26.
Pubmed: 1781355
Jansen JG, Vrieling H, van Zeeland AA, Mohn GR: The gene encoding hypoxanthine-guanine phosphoribosyltransferase as target for mutational analysis: PCR cloning and sequencing of the cDNA from the rat. Mutat Res. 1992 Apr;266(2):105-16. doi: 10.1016/0027-5107(92)90178-5.
Pubmed: 1373820
Taira M, Ishijima S, Kita K, Yamada K, Iizasa T, Tatibana M: Nucleotide and deduced amino acid sequences of two distinct cDNAs for rat phosphoribosylpyrophosphate synthetase. J Biol Chem. 1987 Nov 5;262(31):14867-70.
Pubmed: 2822704
Ishijima S, Taira M, Tatibana M: Complete cDNA sequence of rat phosphoribosylpyrophosphate synthetase subunit I (PRS I). Nucleic Acids Res. 1989 Nov 11;17(21):8860. doi: 10.1093/nar/17.21.8860.
Pubmed: 2555779
Shimada H, Taira M, Yamada K, Iizasa T, Tatibana M: Structure of the rat PRPS1 gene encoding phosphoribosylpyrophosphate synthetase subunit I. J Biol Chem. 1990 Mar 5;265(7):3956-60.
Pubmed: 2154494
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 SMP0000535
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