title: Enantiospecificity of cholesterol function in vivo.
abstract: The importance of the absolute configuration of cholesterol for its function in vivo is unknown. To directly test this question in vivo, we synthesized the enantiomer of cholesterol (ent-cholesterol) and tested its ability to substitute for natural cholesterol (nat-cholesterol) in the growth, viability, and behavior of Caenorhabditis elegans, a cholesterol auxotroph. First-generation animals grown on ent-cholesterol were viable with only mild behavioral defects. However, ent-cholesterol produced 100% lethality/arrest of their second generation progeny. Isotopically labeled ent-cholesterol incorporated into animals, indicating that its lethality was not secondary to cholesterol starvation. When mixed with nat-cholesterol, ent-cholesterol was not inert; rather, it antagonized the activity of nat-cholesterol. These results demonstrate for the first time that the absolute configuration of cholesterol, not just its physical properties, is essential for its functions in vivo.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Crowder
authors.forename: E J
authors.initials: EJ
authors.lastname: Westover
authors.forename: A S
authors.initials: AS
authors.lastname: Kumar
authors.forename: R E
authors.initials: RE
authors.lastname: Ostlund
authors.forename: D F
authors.initials: DF
authors.lastname: Covey
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008956:Models, Chemical; D013997:Time Factors
chemical_list: D002784:Cholesterol