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.

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

1962 ◽  
Vol 40 (12) ◽  
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.

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.

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.

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.

scholarly journals The absolute rate of cholesterol biosynthesis in monocyte-macrophages from normal and familial hypercholesterolaemic subjects

1984 ◽  
Vol 219 (2) ◽  
pp. 461-470 ◽  
Author(s):  
D D Patel ◽  
C R Pullinger ◽  
B L Knight
Keyword(s):  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Cholesterol Biosynthesis ◽  
Specific Radioactivity ◽  
Density Lipoprotein ◽  
Cellular Protein ◽  
True Rate ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
In Cells

The true rate of cholesterogenesis in cultured monocyte-macrophages was determined from the incorporation of [2-14C]acetate into cholesterol, using the desmosterol (cholesta-5,24-dien-3 beta-ol) that accumulated in the presence of the drug triparanol to estimate the specific radioactivity of the newly formed sterols. It was shown that this procedure could be successfully adapted for use with cultured monocytes despite the accumulation of other unidentified biosynthetic intermediates. In cells maintained in 20% (v/v) whole serum approx. 25% of the sterol carbon was derived from exogenous acetate. Cholesterol synthesis was as high in normal cells as in cells from homozygous familial hypercholesterolaemic (FH) subjects and accounted for 50% of the increase in cellular cholesterol. The addition of extra low-density lipoprotein (LDL) reduced cholesterol synthesis, apparently through a decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). When incubated in lipoprotein-deficient serum some cells did not survive, but those that remained showed a normal increase in protein content; the amount of cellular protein and cholesterol in each well did not increase and cholesterol synthesis was reduced by over 80%. HMG-CoA reductase activity fell less dramatically and the proportion of sterol carbon derived from exogenous acetate increased, suggesting that the low rate of cholesterogenesis with lipoprotein-deficient serum was due to a shortage of substrate. The results indicate that under normal conditions monocyte-macrophages obtain cholesterol from endogenous synthesis rather than through receptor-mediated uptake of LDL, and that synthesis together with non-saturable uptake of LDL provides the majority of the cholesterol required to support growth.

scholarly journals Nef Induces Multiple Genes Involved in Cholesterol Synthesis and Uptake in Human Immunodeficiency Virus Type 1-Infected T Cells

2005 ◽  
Vol 79 (15) ◽  
pp. 10053-10058 ◽  
Author(s):  
Angélique B. van ′t Wout ◽  
J. Victor Swain ◽  
Michael Schindler ◽  
Ushnal Rao ◽  
Melissa S. Pathmajeyan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Acetate Incorporation ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Several recent reports indicate that cholesterol might play an important role in human immunodeficiency virus type 1 (HIV-1) replication. We investigated the effects of HIV-1 infection on cholesterol biosynthesis and uptake using microarrays. HIV-1 increased gene expression of cholesterol genes in both transformed T-cell lines and primary CD4+ T cells. Consistent with our microarray data, 14C-labeled mevalonate and acetate incorporation was increased in HIV-1-infected cells. Our data also demonstrate that changes in cholesterol biosynthesis and uptake are only observed in the presence of functional Nef, suggesting that increased cholesterol synthesis may contribute to Nef-mediated enhancement of virion infectivity and viral replication.

Inhibitors of sterol synthesis. Concerning the structure of 15β-methyl-5α,14β-cholest-7-ene-3β,15α-diol, an inhibitor of cholesterol biosynthesis

1988 ◽  
Vol 46 (4) ◽  
pp. 245-251 ◽  
Author(s):  
Samuel T. Bowen ◽  
Edward J. Parish ◽  
William K. Wilson ◽  
George J. Schroepfer ◽  
Florante A. Quiocho
Keyword(s):  
Cholesterol Biosynthesis ◽  
Sterol Synthesis

EFFECT OF ALLOXAN, INSULIN, AND THYROXINE ON CHOLESTEROL AND FATTY ACID SYNTHESIS BY RAT LIVER HOMOGENATES

1957 ◽  
Vol 35 (1) ◽  
pp. 15-23 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Carbon Dioxide ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Rat Liver ◽  
Fatty Acid Synthesis ◽  
Sodium Acetate ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Liver Homogenates ◽  
Vitro Effect

The in vitro effect of alloxan and insulin on the synthesis of cholesterol and fatty acids from 1-C14-sodium acetate by rat liver homogenates has been examined. Alloxan caused a reduction in the incorporation of acetate into cholesterol, fatty acids, and C14O2, but an increase in the oxygen consumption and carbon dioxide production. The addition of insulin to homogenates caused a reduction in cholesterol synthesis but an increase in fatty acid synthesis both for normal and diabetic animals. Homogenates from thyrotoxic rats exhibited a marked reduction in cholesterol synthesis when compared with normal animals. C14O2 production by homogenates from starved rats was appreciably lower than for those from normal animals. With this exception no appreciable difference was found in the oxygen uptake, carbon dioxide, or C14O2 production in homogenates from normal, starved, thyroxine-treated, or diabetic animals. Synthesized cholesterol was found to be located principally in the particulate matter of the homogenates after they had been incubated with 1-C14-sodium acetate. Homogenates from starved rats showed no greater tendency to degrade preformed cholesterol during incubation than did those from normal rats.

ACETATE METABOLISM IN EXPERIMENTAL KETOSIS OF GUINEA PIGS

1961 ◽  
Vol 39 (4) ◽  
pp. 739-746 ◽  
Author(s):  
Frank Sauer
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Guinea Pigs ◽  
Ketone Bodies ◽  
Acid Synthesis ◽  
Sterol Synthesis ◽  
Acetate Metabolism ◽  
Diabetic Ketosis ◽  
Total Fatty Acids ◽  
Experimental Findings

Non-diabetic ketosis was produced experimentally in fasted pregnant guinea pigs. Total CO2output of ketotic animals was less than that of appropriate controls but there was no impairment in the conversion of acetate-1-C14to C14O2. Sterol synthesis increased in ketotic animals while fatty acid synthesis, particularly in carcass, showed the expected decrease. Ketosis was accompanied by an increase in plasma total fatty acids and in the fatty acid concentration of liver. The experimental findings support the hypothesis that ketosis is a manifestation of increased ketogenesis rather than impaired utilization of ketone bodies.

Sign in / Sign up

Export Citation Format

Share Document