Agents affecting lipid metabolism. XXXI. Properties of an inhibitor of cholesterol synthesis present in rabbit liver mitochondria

1968 ◽  
Vol 46 (2) ◽  
pp. 179-187 ◽  
Author(s):  
M. N. Cayen ◽  
D. Dvornik
Keyword(s):  
Cholesterol Synthesis ◽  
Liver Mitochondria ◽  
Aqueous Extracts ◽  
Hepatic Cholesterol ◽  
Large Molecules ◽  
Hepatic Cholesterol Synthesis ◽  
Significant Enrichment ◽  
Liver Homogenates ◽  
Mitochondrial Extract

Aqueous extracts of mitochondria from livers of starved animals have been reported to inhibit hepatic cholesterol synthesis. Some properties of a mitochondrial extract prepared from starved rabbits have been studied. The extract depressed the incorporation of both 2-14C-acetate and 3H-mevalonate into cholesterol by rat liver homogenates, giving concentration–dependent responses. The active factor was unstable to heat, but stable under in vitro incubation conditions, to pH changes, and to storage in the dark and cold. It was cationic and associated with one or more large molecules (mol. wt. 50 000–150 000); it was not cleaved by trypsin digestion. Fractionation experiments did not result in any significant enrichment of inhibitory activity.

IN VIVO INHIBITION OF CHOLESTEROL BIOSYNTHESIS BY A MITOCHONDRIAL EXTRACT

1961 ◽  
Vol 39 (4) ◽  
pp. 747-755 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Liver Mitochondria ◽  
Blood Cholesterol ◽  
Active Principle ◽  
Aqueous Extracts ◽  
Inhibitory Substance ◽  
Cholesterol Levels ◽  
Mitochondrial Extract

Aqueous extracts of liver mitochondria were administered to rats by intraperitoneal, subcutaneous, and oral routes, and C14-acetate or mevalonate was injected intraperitoneally 3 hours later. Cholesterol synthesis in vivo from C14-acetate was depressed by the inhibitory substance in the mitochondrial extracts. Synthesis from C14-mevalonate was not inhibited.Active extracts were prepared from livers of rat, rabbit, pig, and sheep. An inhibitory substance is present in blood serum and administration of active mitochondrial extracts depressed blood cholesterol levels. Pending its identification, the active principle has been provisionally termed I.C.S. (inhibitor of cholesterol synthesis).

Agents affecting lipid metabolism. XXXIX. Effect of combined administration of ethyl chlorophenoxyisobutyrate and cholestyramine on cholesterol biosynthesis in the rat

1970 ◽  
Vol 48 (9) ◽  
pp. 1022-1023 ◽  
Author(s):  
M. N. Cayen ◽  
D. Dvornik
Keyword(s):  
Lipid Metabolism ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Combined Effect ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis ◽  
Combined Administration ◽  
Liver Homogenates

Rats were fed ethyl p-chlorophenoxyisobutyrate (CPIB) and cholestyramine, alone and in combination. Regarding levels of circulating cholesterol, cholestyramine had no effect, while a fall was observed with CPIB given alone or in combination with cholestyramine. Subsequently, the combined effect of both agents was elicited by measuring the incorporation of 2-14C-acetate into cholesterol by liver homogenates of treated rats; addition of CPIB decreased the cholestyramine-induced increase in the rate of hepatic cholesterol synthesis.

Agents affecting lipid metabolism. XXXII. Effect of a liver mitochondrial extract on cholesterol synthesis in the rat

1968 ◽  
Vol 46 (2) ◽  
pp. 189-191
Author(s):  
M. N. Cayen ◽  
P. Hill ◽  
D. Dvornik
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Crude Extract ◽  
Cholesterol Synthesis ◽  
Liver Mitochondria ◽  
Liver Cholesterol ◽  
Acetate Incorporation ◽  
Hepatic Cholesterol ◽  
Experimental Conditions ◽  
Mitochondrial Extract

A lyophilized extract was prepared from liver mitochondria of rabbits starved for 24 h. Rats were fed single oral (1–4 g/kg body weight) and intraperitoneal (1.5 g/kg) doses of the crude extract. After 3 h, the livers of one group were removed and 2-14C-acetate incorporation into cholesterol was measured. In the second group, rats received an interperitoneal dose of 2-14C-acetate 1 h after administration of the mitochondrial extract; animals were sacrificed 2 h later and the incorporation into hepatic cholesterol was measured. Under these experimental conditions, administration of the mitochondrial extract did not decrease the incorporation of 2-14C-acetate into liver cholesterol.

FURTHER STUDIES WITH THE MITOCHONDRIAL INHIBITOR OF CHOLESTEROL SYNTHESIS

1964 ◽  
Vol 42 (1) ◽  
pp. 105-110 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Aqueous Extract ◽  
Inhibitory Activity ◽  
Protein Fraction ◽  
Cholesterol Synthesis ◽  
Liver Homogenate ◽  
Liver Mitochondria ◽  
Active Principle ◽  
Mitochondrial Extract ◽  
Mitochondrial Inhibitor

The inhibitory activity of an aqueous extract of liver mitochondria (I.C.S.) was observed with Triton-treated rats. Fractionation of I.C.S. on Sephadex indicated that the active principle comes off the Sephadex with the protein fraction. Inhibitory activity was shown to be present in the 100,000 × g supernate of the liver homogenate of a starved rat, indicating that the active principle moves from the mitochondrion to the surrounding cytoplasm.Electrodialysis of the mitochondrial extract revealed that the inhibitor is permeable and moves to the cathode. The electrodialyzed material was found to be active as an inhibitor of cholesterol synthesis in vitro and in vivo.It is concluded that the active principle is associated with protein and may be separated therefrom by electrodialysis.

Increased hepatic cholesterol synthesis in normal rats by cross-circulation with ileal bypassed partners

1979 ◽  
Vol 34 (4) ◽  
pp. 383-389 ◽  
Author(s):  
Philip D. Schneider ◽  
Ignacio J. Guzman ◽  
Richard D. Rucker ◽  
Thomas G. Stocks ◽  
Richard L. Varco ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis
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