DIURNAL VARIATION AND CHOLESTEROL REGULATION OF HEPATIC HMG-COA REDUCTASE ACTIVITY

HMG-CoA reductase exhibits a diurnal rhythm. Cycloheximide injection completely prevents both the observed 9.5 fold rise in activity and the loss of activity during daylight. This is compatible with the existence of a specific, labile,degradative or inactivating protein for HMG-CoA reductase. Effects of cholesterol on reductase activity were also studied. KM and Vmax for reductase from normal- and cholesterol-fed rats are 8.1×10-5 M and 0.33 nmole/min/mg and 6.9x10-5 M and 0.0404 nmole/min/mg respectively. Reductase from both sources is substrate-inhibited by HMG-CoA. Mixing experiments suggest that a soluble inhibitor of IM -CoA reductase does not cause the profound drop in activity observed in cholesterol-fed rats. © 1969.