The effects of microsomal HMG-CoA reductase kinase, cytosolic phosphoprotein phosphatase and cytosolic, thioldependent cholesterol 'la-hydroxylase stimulatory protein on purified cholesterol 7a-hydroxylase and HMG-CoA reductase from rat liver were compared. Neither HMG-CoA reductase kinase nor phosphoprotein phosphatase had any significant effect on cholesterol 7a-hydroxylase activity. They inhibited and stimulated, respectively, the activity of HMG-CoA reductase. The purified cytosolic protein which stimulated cholesterol 'la-hydroxylase threefold in the presence of glutathione had no effect on HMG-CoA reductase. The results show that there are separate intracellular systems for modulation of cholesterol 7a-hydroxylase and HMG-CoA reductase.

The ability of different lipid-binding proteins in liver cytosol to affect enzyme activities in bile-acid biosynthesis was studied in whole microsomes (microsomal fractions) and mitochondria and in purified enzyme systems. Sterol carrier protein2 stimulated the 7a-hydroxylation of cholesterol and the 12a-hydroxylation of 5,-cholestane-3a,7a-diol in microsomes and the 26-hydroxylation of cholesterol in mitochondria 2-3-fold. It also stimulated the oxidation of 5-cholestene-3,/,7a-diol into 7a-hydroxy-4-cholesten-3-one in microsomes. The stimulatory effect of sterol carrier protein2 was much less with purified cholesterol 7a-and 26-hydroxylase systems than with microsomes and mitochondria. No stimulatory effect of sterol carrier protein2 was observed with purified 12a-hydroxylase and 3,#-hydroxy-A5-C27-steroid