Harris B E, Song R L, He Y J, Soong S J, Diasio R B
Department of Pharmacology, University of Alabama at Birmingham 35294.
Biochem Pharmacol. 1988 Dec 15;37(24):4759-62. doi: 10.1016/0006-2952(88)90349-8.
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.
二氢嘧啶脱氢酶（DPD）是嘧啶分解代谢中的初始限速酶，在处于标准化明暗条件下饲养的大鼠肝脏中，于24小时内的不同时间测量其活性。在“正常”条件下，即上午6:00至下午6:00开灯，下午6:00至上午6:00关灯，观察到DPD活性存在昼夜节律（余弦分析，P小于0.0001），活性峰值出现在下午4:00（2.96纳摩尔分解代谢产物/分钟/毫克），谷值出现在凌晨4:00（0.40纳摩尔分解代谢产物/分钟/毫克）。最大酶活性超过最小活性7倍以上。颠倒明暗周期（即下午6:00至上午6:00开灯，上午6:00至下午6:00关灯）导致酶活性相应改变。在这些“颠倒”条件下，观察到昼夜节律（余弦分析，P小于0.0001），活性峰值出现在上午6:00（2.87纳摩尔分解代谢产物/分钟/毫克），谷值出现在下午6:00（0.92纳摩尔分解代谢产物/分钟/毫克）。这些研究表明，大鼠肝脏中的DPD活性在24小时内随明暗周期而变化。
