Previous section Next section
Degradation of pyrimidines is essentially the reverse of synthesis
Body_ID: HC029017
page 420
0
page 421
Body_ID: P0421
MEASUREMENT OF OROTIC ACID IN URINE
Body_ID: B029006
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.
Body_ID: PB29010
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.
Body_ID: P029034
Previous section
Bar end Bar end
Next section
Copyright © 2007 Elsevier Inc. All rights reserved. Read our Terms and Conditions of Use and our Privacy Policy.
For problems or suggestions concerning this service, please contact: studentconsult.help@elsevier.com