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.

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.

scholarly journals Conversion of 5-aminolaevulinate into haem by liver homogenates. Comparison of rat and chick embryo

1981 ◽  
Vol 198 (3) ◽  
pp. 595-604 ◽  
Author(s):  
J F Healey ◽  
H L Bonkowsky ◽  
P R Sinclair ◽  
J F Sinclair
Keyword(s):  
Chick Embryo ◽  
Rat Liver ◽  
Biosynthetic Pathway ◽  
Frozen Storage ◽  
Relevant Information ◽  
Porphobilinogen Deaminase ◽  
Embryo Liver ◽  
Liver Homogenates ◽  
Rate Limiting ◽  
Kinetics Of

1. We have studied the kinetics of the conversion of 5-aminolaevulinate into haem and haem precursors in homogenates of livers of rats and chick embryos. Homogenates of fresh liver from both species efficiently convert 5-aminolaevulinate into haem. After frozen storage for 1 year, homogenates of rat, but not chick, liver have decreased rates of formation of haem with accumulation of more protoporphyrin. The rate of haem formation after storage is restored by addition of Fe2+ and menadione. 2. At all initial concentrations of 5-aminolaevulinate tested (2 microM-1 mM), homogenates of rat liver accumulate less protoporphyrin than haem. In contrast, homogenates of chick embryo liver accumulate more protoporphyrin than haem at concentration of 5-aminolaevulinate greater than 10 microM. Conversion of protoporphyrin into haem by homogenates of fresh or frozen chick embryo liver is not increased by addition of Fe2+. 3. Homogenates of liver from both species accumulate porphobilinogen; the kinetic parameters for this process reflect those of 5-aminolaevulinate dehydratase. 4. The results show that the rate-limiting enzyme for the hepatic conversion of 5-aminolaevulinate into protoporphyrin is porphobilinogen deaminase. In addition, chick liver, compared with rat liver, has only about one-fifth the activity of ferrochelatase, the final enzyme of the haem biosynthetic pathway, which inserts Fe2+ into protoporphyrin to form haem. 5. Comparison of these results with previous studies indicates that the homogenate system described here provides physiologically and clinically relevant information for study of hepatic haem synthesis and its control.

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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