Acetyl-CoA hydrolase: relation between activity and cholesterol metabolism in rat.
To examine whether cytosolic acetyl-CoA hydrolase in rat liver is involved in regulation of cholesterol biosynthesis, we investigated the alteration of the enzyme activity under conditions of stimulation (cholestyramine treatment) and suppression [cholesterol feeding, a potent competitive inhibitor of microsomal 3-hydroxy-3-methylglutaryl-CoA reductase (CS 514) treatment, and a hypolipidemic drug [alpha-(p-chlorophenoxy)isobutyric acid, CPIB] injection) of cholesterol biosynthesis. The enzyme activity in rat liver increased significantly in the early diabetic, cholesterol-fed, CS 514-, and CPIB-treated groups, but no change in its activity was observed in chronic diabetic groups. Cholestyramine treatment to cholesterol-fed rats made the enzyme activity return to the initial level. When chronic diabetic rats were given a cholesterol diet or treated with CS 514 or CPIB, the activity increased significantly. Inhibition of cholesterol biosynthesis caused by these treatments induced increase in the enzyme activity with increase in the enzyme protein, judging from results obtained by enzyme-linked immunosorbent assay. These results suggest that this enzyme has a physiological role in maintenance of the equilibrium between the cytosolic acetyl-CoA concentration and CoA-SH pool for cholesterol metabolism.
D000104:Acetyl-CoA Hydrolase / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology; D002792:Cholestyramine Resin / Q000494:pharmacology; D002995:Clofibric Acid / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D017035:Pravastatin; D051381:Rats; D013869:Thiolester Hydrolases / Q000378:metabolism*
D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D002792:Cholestyramine Resin; D002995:Clofibric Acid; D002784:Cholesterol; D013869:Thiolester Hydrolases; D000104:Acetyl-CoA Hydrolase; D017035:Pravastatin