AJP - Regulatory, Integrative and Comparative Physiology, Vol 255, Issue 5 724-R730, Copyright © 1988 by American Physiological Society
Acetyl-CoA hydrolase: relation between activity and cholesterol metabolism in rat
S. Ebisuno, F. Isohashi, Y. Nakanishi and Y. Sakamoto
Department of Oncology, Osaka University Medical School, Japan.
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.
