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Urinary uracil concentrations are a useful guide to genetic disorders associated with neurological deficits and abnormal pyrimidine metabolism
Author(s) -
Davies P.M.,
Fairbanks L.D.,
Dulby J.A.,
Simmonds H.A.
Publication year - 1997
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005332606213
Subject(s) - uracil , orotic acid , pyrimidine metabolism , urea cycle , pyrimidine , dihydropyrimidine dehydrogenase , thymine , biochemistry , ornithine carbamoyltransferase , purine , chemistry , enzyme , biology , medicine , ornithine , genetics , thymidylate synthase , cancer , dna , fluorouracil , amino acid , arginine
Elevated urinary uracil concentrations are characteristic of genetic deficiencies of enzymes catalysing the first two steps of the pyrimidine degradative pathway (Van Gennip et al 1993), dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHP). DPD is rate limiting for the whole pathway. Homozygotes are detected by the raised levels of uracil and thymine in urine. The pyrimidine synthetic route shares a common intermediate. carbamoyl phosphate, with the urea cycle. In urea‐cycle disorders such as ornithine carbamoyltransferase (OCT) deficiency, orotic aciduria resulting from an increased flux through the pathway has been used to detect hemizygotes or carriers following a protein, or more recently, an allopurinol load (Sebesta et al 1994). This paper demonstrates that uracil may be an even more useful guide to OCT carrier status and compares urinary uracil with concentrations found in genetic pyrimidine defects associated with neurological deficits.