Enantiospecificity of Cholesterol Function in Vivo

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, vi...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-11, Vol.276 (48), p.44369-44372
Main Authors: Crowder, C M, Westover, E J, Kumar, A S, Ostlund, Jr, R E, Covey, D F
Format: Article
Language:English
Subjects:
Animals
Caenorhabditis elegans - metabolism
Cholesterol - chemistry
Cholesterol - metabolism
Cholesterol - physiology
Dose-Response Relationship, Drug
Models, Chemical
Time Factors
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Summary: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 .
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C100535200