Circadian rhythm of rat liver dihydropyrimidine dehydrogenase. Possible relevance to fluoropyrimidine chemotherapy.
The activity of dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting enzyme in pyrimidine catabolism, was measured at various times over a 24-hr period in the livers of rats housed under standardized conditions of light and dark. Under "normal" conditions, i.e. lights on from 6:00 a.m. to 6:00 p.m. and off from 6:00 p.m. to 6:00 a.m., a circadian rhythm of DPD activity was observed (P less than 0.0001, Cosinor analysis) with the peak of activity at 4:00 p.m. (2.96 nmol catabolites/min/mg) and the trough at 4:00 a.m. (0.40 nmol catabolites/min/mg). Maximum enzyme activity exceeded minimum activity by more than 7-fold. Reversing the light-dark cycle (i.e. lights on from 6:00 p.m. to 6:00 a.m. and off from 6:00 a.m. to 6:00 p.m.) resulted in a corresponding shift in enzyme activity. Under these "reverse" conditions, a circadian rhythm was observed (P less than 0.0001, Cosinor analysis) with the peak of activity at 6:00 a.m. (2.87 nmol catabolites/min/mg) and the trough at 6:00 p.m. (0.92 nmol catabolites/min/mg). These studies demonstrated that DPD activity in rat liver varies over a 24-hr period in association with the light-dark cycle.
Harris
B E
BE
Department of Pharmacology, University of Alabama at Birmingham 35294.
Song
R L
RL
He
Y J
YJ
Soong
S J
SJ
Diasio
R B
RB
D000818:Animals; D002940:Circadian Rhythm; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil / Q000378:metabolism*; D066298:In Vitro Techniques; D008027:Light; D008099:Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats
D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil