Kopito R R, Weinstock S B, Freed L E, Murray D M, Brunengraber H
J Lipid Res. 1982 May;23(4):577-83.
A circadian rhythm in plasma mevalonate was identified in human subjects. This variation, over a 5-fold range, is paralleled by a rhythm in urinary excretion. No such diurnal change in plasma mevalonate was observed in schedule-fed, light-cycled rats, despite the presence of a pronounced rhythm in liver HMG-Coa reductase and sterol synthesis. A linear correlation was found between liver HMG-CoA reductase activity and the rate of hepatic sterol synthesis. Sterol synthesis accounted for 59% of the HMG-CoA reductase activity. A 4-fold increase in plasma mevalonate following bilateral nephrectomy did not feed back on liver HMG-CoA reductase. Turnover rates for circulating R- and S-mevalonate were determined by the kinetics of tritiated tracers. S-Mevalonate exhibited first-order kinetics with a T 1/2 of 19 to 23 min, while R-mevalonate kinetics could be resolved into two phases with half-lives of 9 and 42 min. The renal uptake of circulating mevalonate was measured by the initial rate of increase in plasma mevalonate immediately following bilateral nephrectomy; this was confirmed by determination of the renal arterio-venous difference. This value ranges between 500 and 600 pmol/min for a 250-g rat.
在人类受试者中发现血浆甲羟戊酸存在昼夜节律。这种在5倍范围内的变化与尿排泄节律平行。在按时间表喂食、有光照周期的大鼠中，未观察到血浆甲羟戊酸有这种昼夜变化，尽管肝脏3-羟基-3-甲基戊二酰辅酶A还原酶和甾醇合成存在明显节律。发现肝脏3-羟基-3-甲基戊二酰辅酶A还原酶活性与肝脏甾醇合成速率之间存在线性相关性。甾醇合成占3-羟基-3-甲基戊二酰辅酶A还原酶活性的59%。双侧肾切除术后血浆甲羟戊酸增加4倍，并未对肝脏3-羟基-3-甲基戊二酰辅酶A还原酶产生反馈作用。通过氚标记示踪剂的动力学测定循环R-和S-甲羟戊酸的周转率。S-甲羟戊酸呈现一级动力学，半衰期为19至23分钟，而R-甲羟戊酸动力学可分为两个阶段，半衰期分别为9分钟和42分钟。通过双侧肾切除术后血浆甲羟戊酸立即增加的初始速率来测量循环甲羟戊酸的肾脏摄取；通过测定肾动静脉差异证实了这一点。对于一只250克的大鼠，该值在500至600皮摩尔/分钟之间。
