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Pathway Description
UMP Synthase Deficiency (Orotic Aciduria)
Homo sapiens
Disease Pathway
Orotic aciduria, also known as UMP synthase deficiency, is an autosomal recessive disorder of pyrimidine metabolism caused by a defective uridine monophosphate synthetase (UMPS). UMPS is a multifunctional protein which carries out the functions of both orotate phosphoribosyltransferase (OPRT) and orotidine 5'-phosphate decarboxylase (ODC). UMPS catalyzes the conversion of orotic acid into uridine monophosphate (UMP) which is a nucleotide incorporated into ribonucleic acid (RNA). This disease is characterized by a very large accumulation of orotic acid in the urine, occasionally causing urinary obstruction. Symptoms of the disease include megaloblastic anemia as well as retarded growth and development.
References
UMP Synthase Deficiency (Orotic Aciduria) References
[OMIM: Entry 258900](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=258900)
[Wikipedia: Uridine monophosphate synthetase](http://en.wikipedia.org/wiki/Uridine_monophosphate_synthetase)
[Uniprot: A8K5J1](http://www.uniprot.org/uniprot/A8K5J1)
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.99 Heilbronn: SPS Verlagsgesellschaft
Becroft DM, Phillips LI, Simmonds A: Hereditary orotic aciduria: long-term therapy with uridine and a trial of uracil. J Pediatr. 1969 Nov;75(5):885-91.
Pubmed: 5347440
Qumsiyeh MB, Valentine MB, Suttle DP: Localization of the gene for uridine monophosphate synthase to human chromosome region 3q13 by in situ hybridization. Genomics. 1989 Jul;5(1):160-2.
Pubmed: 2767686
Suchi M, Mizuno H, Kawai Y, Tsuboi T, Sumi S, Okajima K, Hodgson ME, Ogawa H, Wada Y: Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families. Am J Hum Genet. 1997 Mar;60(3):525-39.
Pubmed: 9042911
Winkler JK, Suttle DP: Analysis of UMP synthase gene and mRNA structure in hereditary orotic aciduria fibroblasts. Am J Hum Genet. 1988 Jul;43(1):86-94.
Pubmed: 2837086
Orotic aciduria. Nutr Rev. 1969 May;27(5):142-4.
Pubmed: 4893711
Pyrimidine 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.
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