Binding of squalene, lanosterol, desmosterol, and cholesterol to proteins in brain and liver 105,000 g supernatant fractions: evidence for specific binding sites.
The binding of squalene, lanosterol, desmosterol, and cholesterol to proteins in 105,000 g supernatant fraction (S105) from brain and liver of rats was investigated. The S105 fractions from both tissues contain specific binding sites for sterols, which are sensitive to trypsin. The dissociation constants for squalene and sterol protein complexes were in the range of 10(-6) M and were not appreciably different for proteins in brain and liver S105. Competition studies revealed that both brain and liver S105 contain one receptor protein which binds lanosterol and is specific for methyl sterols, and a second receptor which binds both desmosterol and cholesterol. Binding of 7-dehydrocholesterol reported by others must occur at a third independent site since this compound does not interfere with the binding of lanosterol, desmosterol, or cholesterol. Although binding of squalene to proteins in brain and liver S105 does occur, we were unable to show the specificity of squalene binding. The concentration of desmosterol and cholesterol binding sites, which ranged from 6 to 10 nmol/mg protein, was 3- to 5-fold higher than the concentration of squalene and lanosterol binding sites (1.6-2.3 nmol/mg protein). The brain S105 from suckling rats contained fewer binding sites for desmosterol and cholesterol than the brain S105 from weaned rats. However, the concentration of lanosterol binding sites in brain S105 did not show an age-dependent change. The receptor proteins in brain and liver appear to be identical.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003897:Desmosterol / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D007810:Lanosterol / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008798:Mevalonic Acid / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011987:Receptors, Steroid / Q000378:metabolism*; D013185:Squalene / Q000378:metabolism*
D011987:Receptors, Steroid; D007810:Lanosterol; D003897:Desmosterol; D013185:Squalene; D002784:Cholesterol; D008798:Mevalonic Acid