The influence of cholesterol precursor--desmosterol--on artificial lipid membranes

Biochim Biophys Acta. 2015 Aug;1848(8):1639-45. doi: 10.1016/j.bbamem.2015.04.017. Epub 2015 May 7.

Abstract

The disorders in cholesterol biosynthesis pathway and various diseases manifest in the accumulation of cholesterol precursors in the human tissues and cellular membranes. In this paper the effect of desmosterol--one of cholesterol precursors--on model lipid membranes was studied. The investigations were performed for binary SM/desmo and POPC/desmo and ternary SM/POPC/desmo monolayers. Moreover, the experiments based on the gradual substitution of cholesterol by desmosterol in SM/POPC/chol=1:1:1 system were done. The obtained results allowed one to conclude that desmosterol is of lower domains promoting and stabilizing properties and packs less tightly with the lipids in monolayers. Moreover, desmosterol probably could replace cholesterol in model membranes, but only at its low proportion in the system (2%), however, at a higher degree of cholesterol substitution a significant decrease of the monolayer stability and packing and alterations in the film morphology were detected. The results collected in this work together with those from previous experiments allowed one to analyze the effect of a double bond in the sterol side chain as well as its position in the ring system on membrane activity of the molecule and to verify Bloch hypothesis.

Keywords: Cholesterol biosynthesis; Desmosterol; Lipid domain; Monolayer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholesterol / chemistry
  • Desmosterol / chemistry*
  • Desmosterol / metabolism
  • Lipid Bilayers*
  • Membranes, Artificial*
  • Molecular Structure
  • Phosphatidylcholines / chemistry
  • Sphingomyelins / chemistry
  • Structure-Activity Relationship

Substances

  • Lipid Bilayers
  • Membranes, Artificial
  • Phosphatidylcholines
  • Sphingomyelins
  • Desmosterol
  • Cholesterol
  • zymosterol
  • 1-palmitoyl-2-oleoylphosphatidylcholine