Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1971 Jan;121(1):131–137. doi: 10.1042/bj1210131

The formation and reduction of the 14,15-double bond in cholesterol biosynthesis

I A Watkinson 1, D C Wilton 1, K A Munday 1, M Akhtar 1
PMCID: PMC1176495  PMID: 4398958

Abstract

It was shown that 100μg quantities of 4,4′-dimethyl[2-3H2]cholesta-8,14-dien-3β-ol (IIIa), tritiated cholesta-8,14-dien-3β-ol, 4,4′-dimethyl[2-3H2]cholesta-7,14-dien-3β-ol, dihydro[2-3H2]lanosterol and [24-3H]lanosterol were converted by a 10000g supernatant of rat liver homogenate into cholesterol in 17%, 54%, 6%, 9.5% and 24% yields respectively. From an incubation of dihydro[3α-3H]lanosterol with a rat liver homogenate in the presence of a trap up to 38% of the radioactivity was found to be associated with a fraction that was unambiguously shown to be 4,4′-dimethylcholesta-8,14-dien-3β-ol. Another related compound, 4,4′-dimethylcholesta-7,14-dien-3β-ol was also shown to be equally effective in its ability to trap compound (IIIa) from an incubation of dihydro[3α-3H]lanosterol. The mechanism of the further conversion of the compound (IIIa) into cholesterol occurred by the reduction of the 14,15-double bond and involved the addition of a hydrogen atom from the medium to C-15 and another from the 4-position of NADPH to C-14. Two possible mechanisms for the removal of the 14α-methyl group in sterol biosynthesis are discussed.

Full text

PDF
131

Selected References

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

  1. Akhtar M., Hunt P. F., Parvez M. A. The transfer of hydrogen from C-24 to C-25 in ergosterol biosynthesis. Biochem J. 1967 Jun;103(3):616–622. doi: 10.1042/bj1030616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akhtar M., Rahimtula A. D., Watkinson I. A., Wilton D. C., Munday K. A. The status of C-6, C-7, C-15 and C-16 hydrogen atoms in cholesterol biosynthesis. Eur J Biochem. 1969 May 1;9(1):107–111. doi: 10.1111/j.1432-1033.1969.tb00582.x. [DOI] [PubMed] [Google Scholar]
  3. Akhtar M., Rahimtula A. D., Wilton D. C. The incorporation of a hydrogen atom at C-15 of cholesterol biosynthesized from squalene. Biochem J. 1969 Oct;114(4):801–806. doi: 10.1042/bj1140801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Akhtar M., Watkinson I. A., Rahimtula A. D., Wilton D. C., Munday K. A. The role of a cholesta-8,14-dien-3-beta-ol system in cholesterol biosynthesis. Biochem J. 1969 Mar;111(5):757–761. doi: 10.1042/bj1110757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Canonica L., Fiecchi A., Kienle M. G., Scala A., Galli G., Paoletti E. G., Paoletti R. Evidence for the biological conversion of delta 8,14 sterol dienes into cholesterol. J Am Chem Soc. 1968 Nov 6;90(23):6532–6534. doi: 10.1021/ja01025a062. [DOI] [PubMed] [Google Scholar]
  6. Canonica L., Fiecchi A., Kienle M. G., Scala A., Galli G., Paoletti E. G., Paoletti R. The fate of the 15-beta hydrogen of lanosterol in cholesterol biosynthesis. J Am Chem Soc. 1968 Jun 19;90(13):3597–3598. doi: 10.1021/ja01015a074. [DOI] [PubMed] [Google Scholar]
  7. Caspi E., Ramm P. J., Gain R. E. Stereochemistry of tritium at carbon 15 in cholesterol derived from (3R,2R)-2T-mevalonic acid in rat livers. J Am Chem Soc. 1969 Jul 2;91(14):4012–4013. doi: 10.1021/ja01042a090. [DOI] [PubMed] [Google Scholar]
  8. Dempsey M. E. Pathways of enzymic synthesis and conversion to cholesterol of delta-5,7,24-cholestatrien-3 beta-ol and other naturally occurring sterols. J Biol Chem. 1965 Nov;240(11):4176–4188. [PubMed] [Google Scholar]
  9. Fiecchi A., Canonica L., Scala A., Cattabeni F., Paoletti E. G., Paoletti R. 4,4-dimethyl-5-alpha-cholesta-8,14-dien-3-beta-ol. A new precursor of cholesterol in mammalian tissues. Life Sci. 1969 Jun 15;8(12):629–634. doi: 10.1016/0024-3205(69)90219-7. [DOI] [PubMed] [Google Scholar]
  10. GAUTSCHI F., BLOCH K. Synthesis of isomeric 4,4-dimethylcholestenols and identification of a lanosterol metabolite. J Biol Chem. 1958 Dec;233(6):1343–1347. [PubMed] [Google Scholar]
  11. Knight J. C., Klein P. D., Szczepanik P. A. The synthesis of tritium-labeled 14-alpha-methyl-5-alpha-cholest-7-en-3-beta-ol and its enzymatic demethylation. J Biol Chem. 1966 Apr 10;241(7):1502–1508. [PubMed] [Google Scholar]
  12. Lutsky B. N., Schroepfer G. J., Jr Enzymatic conversion of delta8, 14-cholestadien-3beta-ol to cholesterol. Biochem Biophys Res Commun. 1968 Nov 8;33(3):492–496. doi: 10.1016/0006-291x(68)90602-5. [DOI] [PubMed] [Google Scholar]
  13. Wilton D. C., Munday K. A., Skinner S. J., Akhtar M. The biological conversion of 7-dehydrocholesterol into cholesterol and comments on the reduction of double bonds. Biochem J. 1968 Feb;106(4):803–810. doi: 10.1042/bj1060803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wilton D. C., Watkinson I. A., Akhtar M. The stereochemistry of hydrogen transfer from reduced nicotinamide-adenine dinucleotide phosphate in the reduction of ethylenic linkages during cholesterol biosynthesis. Biochem J. 1970 Oct;119(4):673–675. doi: 10.1042/bj1190673. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES