A pivotal role for beta-aminoisobutyric acid and oxidative stress in dihydropyrimidine dehydrogenase deficiency?
Dihydropyrimidine dehydrogenase (DPD) constitutes the first step of the pyrimidine degradation pathway in which the pyrimidine bases uracil and thymine are catabolised to beta-alanine and beta-aminoisobutyric acid (beta-AIB), respectively. The mean concentration of beta-AIB was approximately 5- to 8-fold lower in urine of patients with a DPD deficiency, when compared to age-matched controls. Comparable levels of 8-hydroxydeoxyguanosine (8-OHdG) were present in urine from controls and DPD patients at the age <2 year. In contrast, slightly elevated levels of 8-OHdG were detected in urine from DPD patients with an age >2 year, suggesting the presence of increased oxidative stress.
van Kuilenburg
A B P
AB
Academic Medical Center, University of Amsterdam, Emma Children's Hospital and Department of Clinical Chemistry, Amsterdam, The Netherlands. a.b.vankuilenburg@amc.uva.nl
Stroomer
A E M
AE
Abeling
N G G M
NG
van Gennip
A H
AH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000621:Aminoisobutyric Acids / Q000378:metabolism* / Q000652:urine*; D016022:Case-Control Studies; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D004563:Electrochemistry / Q000379:methods; D006801:Humans; D007223:Infant; D018384:Oxidative Stress; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics
D000621:Aminoisobutyric Acids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C033435:3-aminoisobutyric acid