CGC Bibliography Paper 4986

Enantiospecificity of cholesterol function in vivo.

Crowder CM, Westover EJ, Kumar AS, Ostlund RE, Covey DF

Medline:

11598105

Citation:

Journal of Biological Chemistry 276: 44369-44372 2001

Type:

ARTICLE

Genes:

Abstract:

The importance of the absolute configuration of cholesterol for its function in vivo is unknown. To directly test this question in viva, we synthesized the enantiomer of cholesterol (ent-cholesterol) and tested its ability to substitute for natural cholesterol (not-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 not-cholesterol, ent-cholesterol was not inert; rather, it antagonized the activity of not-cholesterol. These results demonstrate for the first tine that the absolute configuration of cholesterol, not just its physical properties, is essential for its functions in viva.