| Degradation of pyrimidines is essentially the reverse of synthesis
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| MEASUREMENT OF OROTIC ACID IN URINE |
| Orotic aciduria is a symptom of several different metabolic disorders. Urinary orotic acid is usually measured by high performance liquid chromatography (HPLC) with detection at 275 nm; however, this method suffers from a lack of sensitivity and selectivity, i.e., other endogenous components can also absorb at this wavelength. A new analytical method uses liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC/MS/MS). Instead of measuring the absorbance of orotic acid, the mass spectrometer measures products of fragmentation of the orotate molecule, and provides excellent sensitivity and specificity. Although the instrumentation is expensive, sample preparation is simple and inexpensive, and multiple analytes can be measured simultaneously for diagnosis of a wide range of diseases. |
| The pyrimidine monophosphates, CMP, UMP, and TMP, are dephosphorylated to form their respective nucleosides. Cytidine is converted into uridine by action of cytidine deaminase. The ribose moiety of both uridine and thymidine (5-methyl uracil) is removed by action of an enzyme, uridine phosphorylase. The next three steps in the degradation of
pyrimidines are essentially the reverse of the synthetic pathway. The double bond between carbons 5 and 6 is reduced by dihydrouracil dehydrogenase to form dihydrouracil or dihydrothymine. Next the ring is opened by the action of hydropyrimidine hydratase to form β-ureidopropionate or β-ureidoisobutyrate. The enzyme β-ureidopropionase removes ammonia and carbon dioxide to form β-alanine or β-aminoisobutyrate. Finally, following an amino transfer of the β-amino group to α-ketoglutarate, the resulting malonic semialdehyde or methylmalonic semialdehyde can be condensed with CoA for further metabolism.
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