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Pathway Description
5-Oxoprolinuria
Homo sapiens
Disease Pathway
Created: 2013-08-01
Last Updated: 2019-08-30
5-Oxoprolinuria (5-Oxoprolinase deficiency) is a result of a defect in the gamma-glutamyl cycle due to either 5-oxoprolinase or glutathione synthetase deficiency. In the case of glutathione synthetase deficiency, the glycine is not incorporated into gamma-glutamylcysteine. In the case of 5-oxoprolinase, however, pyroglutamic acid accumulates. Symptoms include anemia, mental retardation, metabolic acidosis, respiratory distress and urolithiasis.
References
5-Oxoprolinuria References
[Wikipedia: 5-oxoprolinuria](http://en.wikipedia.org/wiki/5-oxoprolinuria)
[Uniprot: P48637](http://www.uniprot.org/uniprot/P48637)
[OMIM: Entry 266130](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=266130)
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.78 Heilbronn: SPS Verlagsgesellschaft
Divry P, Roulaud-Parrot F, Dorche C, Zabot MT, Contraire B, Hagenfeldt L, Larsson A: 5-Oxoprolinuria (glutathione synthetase deficiency): a case with neonatal presentation and rapid fatal outcome. J Inherit Metab Dis. 1991;14(3):341-4.
Pubmed: 1770788
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Pubmed: 15717202
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Pubmed: 874680
Njalsson R: Glutathione synthetase deficiency. Cell Mol Life Sci. 2005 Sep;62(17):1938-45. doi: 10.1007/s00018-005-5163-7.
Pubmed: 15990954
Van der Werf P, Stephani RA, Orlowski M, Meister A: Inhibition of 5-oxoprolinase by 2-imidazolidone-4-carboxylic acid. Proc Natl Acad Sci U S A. 1973 Mar;70(3):759-61.
Pubmed: 4514988
Glutathione Metabolism References
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.
Lu SC: Glutathione synthesis. Biochim Biophys Acta. 2013 May;1830(5):3143-53. doi: 10.1016/j.bbagen.2012.09.008. Epub 2012 Sep 17.
Pubmed: 22995213
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Pubmed: 9875551
Kaplowitz N, Aw TY, Ookhtens M: The regulation of hepatic glutathione. Annu Rev Pharmacol Toxicol. 1985;25:715-44. doi: 10.1146/annurev.pa.25.040185.003435.
Pubmed: 3890714
Forman HJ, Zhang H, Rinna A: Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009 Feb-Apr;30(1-2):1-12. doi: 10.1016/j.mam.2008.08.006. Epub 2008 Aug 30.
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Bachhawat AK, Thakur A, Kaur J, Zulkifli M: Glutathione transporters. Biochim Biophys Acta. 2013 May;1830(5):3154-64. doi: 10.1016/j.bbagen.2012.11.018. Epub 2012 Nov 30.
Pubmed: 23206830
Gali RR, Board PG: Sequencing and expression of a cDNA for human glutathione synthetase. Biochem J. 1995 Aug 15;310 ( Pt 1):353-8. doi: 10.1042/bj3100353.
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Uchida M, Sugaya M, Kanamaru T, Hisatomi H: Alternative RNA splicing in expression of the glutathione synthetase gene in human cells. Mol Biol Rep. 2010 Apr;37(4):2105-9. doi: 10.1007/s11033-009-9675-3. Epub 2009 Aug 12.
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Pubmed: 14702039
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Pubmed: 10220143
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Pubmed: 12496980
Sukenaga Y, Ishida K, Takeda T, Takagi K: cDNA sequence coding for human glutathione peroxidase. Nucleic Acids Res. 1987 Sep 11;15(17):7178. doi: 10.1093/nar/15.17.7178.
Pubmed: 3658677
Tutic M, Lu XA, Schirmer RH, Werner D: Cloning and sequencing of mammalian glutathione reductase cDNA. Eur J Biochem. 1990 Mar 30;188(3):523-8. doi: 10.1111/j.1432-1033.1990.tb15431.x.
Pubmed: 2185014
Kelner MJ, Montoya MA: Structural organization of the human glutathione reductase gene: determination of correct cDNA sequence and identification of a mitochondrial leader sequence. Biochem Biophys Res Commun. 2000 Mar 16;269(2):366-8. doi: 10.1006/bbrc.2000.2267.
Pubmed: 10708558
Satoh N, Watanabe N, Kanda A, Sugaya-Fukasawa M, Hisatomi H: Expression of glutathione reductase splice variants in human tissues. Biochem Genet. 2010 Oct;48(9-10):816-21. doi: 10.1007/s10528-010-9362-z. Epub 2010 Jul 14.
Pubmed: 20628807
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Pubmed: 15164054
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
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Pubmed: 18357469
Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A, Ashmun RA, Shapiro LH, Arap W, Ruoslahti E: Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. Cancer Res. 2000 Feb 1;60(3):722-7.
Pubmed: 10676659
Olsen J, Cowell GM, Konigshofer E, Danielsen EM, Moller J, Laustsen L, Hansen OC, Welinder KG, Engberg J, Hunziker W, et al.: Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA. FEBS Lett. 1988 Oct 10;238(2):307-14. doi: 10.1016/0014-5793(88)80502-7.
Pubmed: 2901990
Look AT, Ashmun RA, Shapiro LH, Peiper SC: Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N. J Clin Invest. 1989 Apr;83(4):1299-307. doi: 10.1172/JCI114015.
Pubmed: 2564851
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Pubmed: 8521391
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Pubmed: 8576161
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Pubmed: 8567622
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