scholarly journals The isolation of 2,3-oxidosqualene from the liver of rats treated with 1-dodecylimidazole, a novel hypocholesterolaemic agent

1972 ◽  
Vol 130 (1) ◽  
pp. 153-157 ◽  
Author(s):  
Sandra D. Atkin ◽  
B. Morgan ◽  
K. H. Baggaley ◽  
J. Green
Keyword(s):  
Rat Liver ◽  
Mass Spectra ◽  
Cholesterol Biosynthesis ◽  
Anaerobic Conditions ◽  
Lower Serum ◽  
Unknown Compound ◽  
Lower Serum Cholesterol ◽  
Labelled Compound ◽  
Liver Homogenates ◽  
Hypocholesterolaemic Activity

1. Non-saponifiable lipid from the livers of rats treated with 1-dodecylimidazole contained an unidentified compound that was not present in the livers from untreated animals. 2. Treated rats had lower serum cholesterol concentrations than control rats. 3. 1-Dodecylimidazole, when added to rat liver slices, inhibited the incorporation of [1-14C]acetate and [2-14C]mevalonate into digitonin-precipitable sterols and resulted in the accumulation of a labelled compound, which was chromatographically identical with the unknown compound described in 1 above. 4. Rats treated with 1-dodecylimidazole incorporated less [14C]mevalonate into liver digitonin-precipitable sterols than untreated animals and accumulated the unknown compound as a labelled intermediate. 5. The unknown intermediate had the same chromatographic properties, n.m.r. and mass spectra as authentic 2,3-oxidosqualene. 6. The identity of the intermediate as 2,3-oxidosqualene was further established by showing that it was incorporated into sterols by rat liver homogenates under anaerobic conditions. In addition, incubation of [14C]squalene with rat liver homogenates resulted in trapping of the radioactivity by the added intermediate. 7. It is suggested that the hypocholesterolaemic activity of 1-dodecylimidazole results in part from the inhibition of cholesterol biosynthesis at the level of 2,3-oxidosqualene sterol cyclase.

CHOLESTEROL BIOSYNTHESIS: THE STARVATION BLOCK

1957 ◽  
Vol 35 (1) ◽  
pp. 615-623
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Experimental Evidence ◽  
Rat Liver ◽  
Biosynthetic Pathway ◽  
Glutaric Acid ◽  
Cholesterol Biosynthesis ◽  
Metabolic Block ◽  
Liver Homogenates ◽  
Acidic Compound

Partial localization of the metabolic block in cholesterol biosynthesis from acetate by starved rat liver homogenates has been achieved. Experimental evidence indicates that this block is located in the biosynthetic pathway between β-hydroxy-β-methyl glutaric acid and squalene. Fractionation and comparative chromatographic examination of incubated homogenates from starved and normal rats failed to reveal any accumulation of an appreciably radioactive intermediate as a result of the blocked biosynthetic pathway in the starved animal. A strongly labelled acidic compound has been isolated in minute amounts from incubated homogenates of both starved and normal rats. This is readily incorporated into cholesterol by liver homogenates from normal, but not from starved rats. Its identity has as yet not been established.

CHOLESTEROL BIOSYNTHESIS: THE STARVATION BLOCK

1957 ◽  
Vol 35 (8) ◽  
pp. 615-623 ◽  
Author(s):  
J. F. Scaife ◽  
B. B. Migicovsky
Keyword(s):  
Experimental Evidence ◽  
Rat Liver ◽  
Biosynthetic Pathway ◽  
Glutaric Acid ◽  
Cholesterol Biosynthesis ◽  
Metabolic Block ◽  
Liver Homogenates ◽  
Acidic Compound

Partial localization of the metabolic block in cholesterol biosynthesis from acetate by starved rat liver homogenates has been achieved. Experimental evidence indicates that this block is located in the biosynthetic pathway between β-hydroxy-β-methyl glutaric acid and squalene. Fractionation and comparative chromatographic examination of incubated homogenates from starved and normal rats failed to reveal any accumulation of an appreciably radioactive intermediate as a result of the blocked biosynthetic pathway in the starved animal. A strongly labelled acidic compound has been isolated in minute amounts from incubated homogenates of both starved and normal rats. This is readily incorporated into cholesterol by liver homogenates from normal, but not from starved rats. Its identity has as yet not been established.

METABOLISM OF 17α-HYDROXYPROGESTERONE-4-14C-17α-CAPROATE BY HOMOGENATES OF RAT LIVER AND HUMAN PLACENTA

1961 ◽  
Vol 36 (4) ◽  
pp. 511-519 ◽  
Author(s):  
Margaret Wiener ◽  
Charles I. Lupa ◽  
E. Jürgen Plotz
Keyword(s):  
Rat Liver ◽  
Human Placenta ◽  
Steric Hindrance ◽  
Placental Tissue ◽  
Caproic Acid ◽  
Major Product ◽  
Side Chain ◽  
Anaerobic Conditions ◽  
Prolonged Action ◽  
Long Acting

ABSTRACT 17α-hydroxyprogesterone-4-14C-17α-caproate (HPC), a long-acting progestational agent, was incubated with homogenates of rat liver and human placenta. The rat liver was found to reduce Ring A of HPC under anaerobic conditions to form allopregnane-3β,17α-diol-20-one-17α-caproate and pregnane-3β,17α-diol-20-one-17α-caproate, the allopregnane isomer being the major product. The caproic acid ester was neither removed nor altered during the incubation. Placental tissue did not attack HPC under conditions where the 20-ketone of progesterone was reduced. It is postulated that this absence of attack on the side chain is due to steric hindrance from the caproate ester, and that this may account for the prolonged action of HPC.

scholarly journals THE INCORPORATION OF THE CARBOXYL CARBON FROM ACETATE INTO CHOLESTEROL BY RAT LIVER HOMOGENATES

1954 ◽  
Vol 206 (1) ◽  
pp. 471-481 ◽  
Author(s):  
Ivan D. Frantz ◽  
Nancy L.R. Bucher ◽  
Henny S. Schneider ◽  
Naomi H. McGovern ◽  
Ruth Kingston
Keyword(s):  
Rat Liver ◽  
Liver Homogenates ◽  
Carboxyl Carbon
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