Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1972 Nov;130(1):153–157. doi: 10.1042/bj1300153

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

Sandra D Atkin 1, B Morgan 1, K H Baggaley 1, J Green 1
PMCID: PMC1174310  PMID: 4655417

Abstract

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.

Full text

PDF
153

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AVIGAN J., STEINBERG D., VROMAN H. E., THOMPSON M. J., MOSETTIG E. Studies of cholesterol biosynthesis. I. The identification of desmosterol in serum and tissues of animals and man treated with MER-29. J Biol Chem. 1960 Nov;235:3123–3126. [PubMed] [Google Scholar]
  2. BUCHER N. L., MCGARRAHAN K. The biosynthesis of cholesterol from acetate-1-C14 by cellular fractions of rat liver. J Biol Chem. 1956 Sep;222(1):1–15. [PubMed] [Google Scholar]
  3. De Matteis F. Stimulation of liver cholesterol synthesis by actinomycin D. Biochem J. 1968 Oct;109(5):775–785. doi: 10.1042/bj1090775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. GOODMAN D. S., POPJAK G. Studies on the biosynthesis of cholesterol. XII. Synthesis of allyl pyrophosphates from mevalonate and their conversion into squalene with liver enzymes. J Lipid Res. 1960 Jul;1:286–300. [PubMed] [Google Scholar]
  5. Siegel A. L., Bowdoin B. C. Modification of an automated procedure for serum cholesterol, which permits the quantitative estimation of cholesterol esters. Clin Chem. 1971 Mar;17(3):229–230. [PubMed] [Google Scholar]
  6. Van Tamelen E. E., Willett J. D., Clayton R. B., Lord K. E. Enzymic conversion of squalene 2,3-oxide to lanosterol and cholesterol. J Am Chem Soc. 1966 Oct 20;88(20):4752–4754. doi: 10.1021/ja00972a058. [DOI] [PubMed] [Google Scholar]
  7. Willett J. D., Sharpless K. B., Lord K. E., van Tamelen E. E., Clayton R. B. Squalene-2,3oxide, an intermediate in the enzymatic conversion of squalene to lanosterol and cholesterol. J Biol Chem. 1967 Sep 25;242(18):4182–4191. [PubMed] [Google Scholar]
  8. Yamamoto S., Bloch K. Enzymatic studies on the oxidative cyclizations of squalene. Biochem Soc Symp. 1970;29:35–43. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES