EFFECT OF STARVATION ON CHOLESTEROL BIOSYNTHESIS IN VITRO

1955 ◽  
Vol 33 (1) ◽  
pp. 858-866 ◽  
Author(s):  
B. B. Migicovsky ◽  
J. D. Wood
Keyword(s):  
Particulate Matter ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Liver Homogenate ◽  
Normal Liver ◽  
Synthetic Activity ◽  
Liver Homogenates

The components of centrifugal fractionation of liver homogenates from normal and starved rats were examined for cholesterol synthesis and inhibition thereof. Normal liver particulate matter fractions obtained between 700 to 9000 × g and 9000 to 140,000 × g were active with respect to cholesterol synthesis in the presence of clear supernate obtained by centrifugation at 140,000 × g. The particles alone did not synthesize cholesterol. Particles from liver homogenate of starved rats, recombined with clear supernate from starved rats, lacked synthetic activity but clear supernate from liver homogenate of starved rats showed some activity in the presence of normal particles. Degradation of cholesterol occurred with liver particles (700–9000 × g) from both normal and starved rats: the latter preparation also inhibited cholesterol synthesis. Preliminary incubation of clear supernate from normal rats with particles from starved rats, followed by recentrifugation at 140,000 × g, produced a supernate with synthetic activity equal to that obtained with untreated supernate. Preliminary incubation with normal particles gave a supernate with less synthetic activity. This indicated another difference between particulate matter from normal and starved rats.

EFFECT OF STARVATION ON CHOLESTEROL BIOSYNTHESIS IN VITRO

1955 ◽  
Vol 33 (5) ◽  
pp. 858-866 ◽  
Author(s):  
B. B. Migicovsky ◽  
J. D. Wood
Keyword(s):  
Particulate Matter ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Liver Homogenate ◽  
Normal Liver ◽  
Synthetic Activity ◽  
Liver Homogenates

The components of centrifugal fractionation of liver homogenates from normal and starved rats were examined for cholesterol synthesis and inhibition thereof. Normal liver particulate matter fractions obtained between 700 to 9000 × g and 9000 to 140,000 × g were active with respect to cholesterol synthesis in the presence of clear supernate obtained by centrifugation at 140,000 × g. The particles alone did not synthesize cholesterol. Particles from liver homogenate of starved rats, recombined with clear supernate from starved rats, lacked synthetic activity but clear supernate from liver homogenate of starved rats showed some activity in the presence of normal particles. Degradation of cholesterol occurred with liver particles (700–9000 × g) from both normal and starved rats: the latter preparation also inhibited cholesterol synthesis. Preliminary incubation of clear supernate from normal rats with particles from starved rats, followed by recentrifugation at 140,000 × g, produced a supernate with synthetic activity equal to that obtained with untreated supernate. Preliminary incubation with normal particles gave a supernate with less synthetic activity. This indicated another difference between particulate matter from normal and starved rats.

AN INCREASED RATE OF CHOLESTEROL BIOSYNTHESIS WITH MICROSOME FRACTIONS OF LIVER FROM KETOTIC GUINEA PIGS

1962 ◽  
Vol 40 (1) ◽  
pp. 1749-1762 ◽  
Author(s):  
F. Sauer
Keyword(s):  
Young Adult ◽  
Guinea Pigs ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Maximum Activity ◽  
Sterol Synthesis ◽  
Differential Centrifugation ◽  
Microsome Fraction ◽  
Liver Homogenates ◽  
Increased Activity

Cholesterol synthesis was studied in liver fractions obtained by differential centrifugation from young, adult, and ketotic guinea pigs. Both 10,000 × g and 105,000 × g sediment was required for maximum activity. Incubations were carried out in the presence of appropriate liver fractions from young guinea pigs in order to overcome the low rates of cholesterol synthesis in liver homogenates from adult guinea pigs. Microsome fractions from ketotic hyperlipemic guinea pigs actively promoted sterol synthesis when incubated with mitochondria plus supernatant from young guinea pigs, while microsome fractions from adult controls (fed or starved) decreased the rate of sterol synthesis in the same incubation system. The results of this investigation indicate that microsomes from hyperlipemic ketotic guinea pigs do not have a block in cholesterol synthesis characteristic of microsomes from starved animals, and that this microsome fraction has increased activity of HMG-CoA2reductase, one of the key enzymes of cholesterol synthesis.

INHIBITION OF CHOLESTEROL FORMATION BY RAT LIVER HOMOGENATES

1955 ◽  
Vol 33 (2) ◽  
pp. 135-138 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Vitamin A ◽  
Rat Liver ◽  
Cholesterol Synthesis ◽  
Liver Homogenate ◽  
Inhibitory Factor ◽  
Normal Rat ◽  
Liver Homogenates

The inability of liver homogenates, from starved and vitamin A deficient rats, to synthesize cholesterol is illustrated. A possible reason for this phenomenon is that these preparations inhibit cholesterol synthesis when added to a liver homogenate from a normal rat. The inhibitory factor or factors are present in both the supernate and residue portions of the homogenate, although the residue matter is more inhibitory.

scholarly journals Aqueous Extracts of Teucrium polium Possess Remarkable Antioxidant Activity In Vitro

2006 ◽  
Vol 3 (3) ◽  
pp. 329-338 ◽  
Author(s):  
Predrag Ljubuncic ◽  
Suha Dakwar ◽  
Irina Portnaya ◽  
Uri Cogan ◽  
Hassan Azaizeh ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Antioxidant Activity ◽  
Rat Liver ◽  
Antioxidant Properties ◽  
Liver Homogenate ◽  
Plasma Oxidation ◽  
Teucrium Polium ◽  
Liver Homogenates ◽  
Β Carotene

Teucrium poliumL. (Lamiaceae) (RDC 1117) is a medicinal plant whose species have been used for over 2000 years in traditional medicine due to its diuretic, diaphoretic, tonic, antipyretic, antispasmodic and cholagogic properties. The therapeutic benefit of medicinal plants is often attributed to their antioxidant properties. We previously reported that an aqueous extract of the leaves and stems of this plant could inhibit iron-induced lipid peroxidation in rat liver homogenate at concentrations that were not toxic to cultured hepatic cells. Others have reported that organic extracts of the aerial components of this plant could inhibit oxidative processes. Against this background, we felt further investigation on the antioxidant action of the extract ofT. poliumprepared according to traditional Arab medicine was warranted. Accordingly, we assessed (i) its ability to inhibit (a) oxidation of β-carotene, (b) 2,2′-azobis(2-amidinopropan) dihydrochloride (AAPH)-induced plasma oxidation and (c) iron-induced lipid peroxidation in rat liver homogenates; (ii) to scavenge the superoxide ($${\hbox{ O }}_{2}^{\bullet -}$$) radical and the hydroxyl radical (OH•); (iii) its effects on the enzyme xanthine oxidase activity; (iv) its capacity to bind iron; and (v) its effect on cell glutathione (GSH) homeostasis in cultured Hep G2 cells. We found that the extract (i) inhibited (a) oxidation of β-carotene, (b) AAPH-induced plasma oxidation (c) Fe2+-induced lipid peroxidation in rat liver homogenates (IC50 = 7 ± 2 μg ml−1); (ii) scavenged $${\hbox{ O }}_{2}^{\bullet -}$$(IC50 = 12 ± 3 μg ml−1) and OH• (IC50 = 66 ± 20 μg ml−1); (iii) binds iron (IC50 = 79 ± 17 μg ml−1); and (iv) tended to increase intracellular GSH levels resulting in a decrease in the GSSG/GSH ratio. These results demonstrate that the extract prepared from theT. poliumpossesses antioxidant activityin vitro. Further investigations are needed to verify whether this antioxidant effect occursin vivo.

Diminished hepatic triiodothyronine production in Gunn rats

1986 ◽  
Vol 113 (2) ◽  
pp. 281-288 ◽  
Author(s):  
J. R. Saltzman ◽  
D. W. Clark ◽  
R. D. Utiger
Keyword(s):  
Thyroid Hormone ◽  
Rat Liver ◽  
Liver Homogenate ◽  
Unconjugated Bilirubin ◽  
Thyroid Hormone Metabolism ◽  
Gunn Rats ◽  
Deiodinase Activity ◽  
Sediment Fraction ◽  
Liver Homogenates

Abstract. The liver is a major site of conversion of thyroxine (T4) to the more active thyroid hormone 3,5,3'-triiodothyronine (T3). Hepatic T4 to T3 conversion is altered by a variety of pathological processes and pharmacological agents. We studied T4 to T3 conversion in glucuronyl transferase deficient homozygous Gunn rats because they have a hepatic enzyme abnormality which leads to hyperbilirubinaemia, and also because they have been reported to have alterations in thyroid hormone metabolism. An in vitro incubation system employing the 10 000 × g supernatant of liver homogenate was used, and T3 production was measured by radioimmunoassay. Experiments were done using substrate concentrations ranging from 0.56 to 20 μm, tissue protein in concentrations ranging from 0.625 to 20 mg and incubation times of 15 to 60 min. T3 production by liver homogenates from homozygous Gunn rats in these studies ranged from 29 to 70% of that produced by liver homogenates from phenotypically normal heterozygous Gunn rats. The deficit in hepatic T3 production by homozygous rats could not be overcome by increasing cofactor concentrations. After ultracentrifugation at 100 000 μ g, T4-5'-deiodinase activity was found primarily in the 100 000 × g sediment fraction. Homogygous rat liver 100 000 × g sediment T3 production was 55% of that of the heterozygous rat liver 100 000 × g sediment. Liver cytosol from both homozygous and heterozygous rats inhibited microsomal T4-5'-deiodinase activity similarly. Addition of unconjugated bilirubin to liver homogenates resulted in reduction of T3 production in livers from both homozygous and heterozygous rats. Thus the diminished capacity for hepatic conversion of T4 to T3 in homozygous Gunn rats may be due to inhibition of T4-5'-deiodinase activity by high endogenous levels of unconjugated bilirubin.

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.

INHIBITION OF CHOLESTEROL BIOSYNTHESIS BY A MITOCHONDRIAL EXTRACT

1960 ◽  
Vol 38 (4) ◽  
pp. 339-346 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Inhibitory Effect ◽  
Homeostatic Mechanism ◽  
Heat Labile ◽  
Mitochondrial Extract

Cholesterol biosynthesis was effectively inhibited by an extract of mitochondria disrupted with sonic oscillations. The inhibitory effect occurred both in vivo and in vitro. The inhibitor substance was heat-labile, and could be prepared from mitochondria from livers of normal or starved rats. The inhibition appeared to be of the competitive type. The locus of the inhibition in the chain of reactions from acetate to cholesterol appeared to be between acetoacetate and mevalonate. It is suggested that the inhibitor substance present in the mitochondrion represents, in part, the homeostatic mechanism that controls cholesterol synthesis by the liver.

scholarly journals Effect of 26-Oxygenosterols from Ganoderma lucidum and Their Activity as Cholesterol Synthesis Inhibitors

2005 ◽  
Vol 71 (7) ◽  
pp. 3653-3658 ◽  
Author(s):  
Hassan Hajjaj ◽  
Catherine Macé ◽  
Matthew Roberts ◽  
Peter Niederberger ◽  
Laurent B. Fay
Keyword(s):  
Ganoderma Lucidum ◽  
Cholesterol Synthesis ◽  
Biological Effects ◽  
Cholesterol Biosynthesis ◽  
Blood Cholesterol ◽  
Ganoderic Acid ◽  
Isolation And Identification ◽  
Medicinal Fungus ◽  
Lower Blood Cholesterol

ABSTRACT Ganoderma lucidum is a medicinal fungus belonging to the Polyporaceae family which has long been known in Japan as Reishi and has been used extensively in traditional Chinese medicine. We report the isolation and identification of the 26-oxygenosterols ganoderol A, ganoderol B, ganoderal A, and ganoderic acid Y and their biological effects on cholesterol synthesis in a human hepatic cell line in vitro. We also investigated the site of inhibition in the cholesterol synthesis pathway. We found that these oxygenated sterols from G. lucidum inhibited cholesterol biosynthesis via conversion of acetate or mevalonate as a precursor of cholesterol. By incorporation of 24,25-dihydro-[24,25-3H2]lanosterol and [3-3H]lathosterol in the presence of ganoderol A, we determined that the point of inhibition of cholesterol synthesis is between lanosterol and lathosterol. These results demonstrate that the lanosterol 14α-demethylase, which converts 24,25-dihydrolanosterol to cholesterol, can be inhibited by the 26-oxygenosterols from G. lucidum. These 26-oxygenosterols could lead to novel therapeutic agents that lower blood cholesterol.

A POSSIBLE MECHANISM FOR FATTY ACID INHIBITION OF CHOLESTEROL SYNTHESIS

1957 ◽  
Vol 35 (1) ◽  
pp. 645-653
Author(s):  
J. D. Wood ◽  
B. B. Migicovsky
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Synthesis ◽  
Unsaturated Fatty Acids ◽  
Cholesterol Biosynthesis ◽  
Saturated Fatty Acids ◽  
Liver Homogenate ◽  
Acid Inhibition ◽  
Acetyl Coa ◽  
Fatty Acid Inhibition

Further investigations have been carried out on the fatty acid inhibition of cholesterol biosynthesis in rat liver homogenates. A correlation appears to exist between cholesterol inhibition and the elongation of the carbon chain of saturated fatty acids containing an even number of carbon atoms. Neither saturated nor unsaturated fatty acids interfere with the formation of acetyl CoA by liver homogenate. The stage where acetoacetate is formed from acetyl CoA is suggested as a possible site for inhibition of cholesterol synthesis by fatty acids.

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.

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