Relation between cholesterol 7a-hydroxylase and HMG-CoA reductase

There is a close relation between cholesterol 7a-hydroxylase and HMG-CoA reductase. The two enzymes are located near each other on the endoplasmic reticulum and newly synthesized cholesterol seems to be the preferred substrate for the cholesterol 7a-hydroxylase. 

In an early work by Myant and Eder, a time lag was observed between the increase in synthesis of cholesterol and synthesis of bile acids [221]. Such a time lag has not been reported in later studies, and it seems likely that the two rate-limiting enzymes respond to the same signal. The possibility that an increase of available cholesterol is responsible for the increase of cholesterol 7a-hydroxylation seems excluded by the work by Mitropoulos et al. in which attempts were made to measure the substrate of the enzyme under different condition [59,222]. In view of the time lag between introduction of a bile fistula and rise of enzyme activities, it is likely that protein synthesis is involved in the increase of both enzyme activities. 

Since very little bile acids are transported via the lymph [224], the increased cholesterol 7a-hydroxylase activity observed after lymphatic drainage [225] is not due to depletion of bile acids. In view of the fact that the synthesis of cholesterol increases after lymphatic drainage, it is possible that the increased 7a-hydroxylation in this case may be due to increased supply of newly synthesized cholesterol. 

The diurnal rhythm in both cholesterol 7a-hydroxylase and HMG-CoA reductase 

---