24(S),25-Epoxycholesterol. Evidence consistent with a role in the regulation of hepatic cholesterogenesis

• Published in: The Journal of biological chemistry Vol. 260; no. 25; pp. 13391 - 13394
• Main Authors: Spencer, T A, Gayen, A K, Phirwa, S, Nelson, J A, Taylor, F R, Kandutsch, A A, Erickson, S K
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 05-11-1985; American Society for Biochemistry and Molecular Biology
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cholesterol - analogs & derivatives; Cholesterol - analysis; Cholesterol - biosynthesis; Cholesterol - physiology; Chromatography, High Pressure Liquid; Fundamental and applied biological sciences. Psychology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Liver - analysis; Liver - metabolism; Other biological molecules; Cell culture; Regulation(control); Liver; Biosynthesis; Metabolism; Fibroblast; Cholesterol
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)38732-X

Previously we showed that 24(S),25-epoxycholesterol is formed from acetate, via squalene 2,3(S),22(S),23-dioxide and 24(S),25-oxidolanosterol, during the normal course of cholesterol biosynthesis in S10 rat liver homogenate (Nelson, J. A., Steckbeck, S. R., and Spencer, T. A. (1981) J. Biol. Chem. 256, 1067-1068; Nelson, J. A., Steckbeck, S. R., and Spencer, T. A. (1981) J. Am. Chem. Soc. 103, 6974-6975). Herein we demonstrate that the nonsaponifiable extract from human liver tissue contains 24(S),25-epoxycholesterol in an amount approximately 10(-3) relative to cholesterol. We show that 24(S),25-epoxycholesterol, like many other oxygenated sterols, represses hydroxymethylglutaryl-CoA reductase activity in cultured cells and binds to the cytosolic oxysterol-binding protein. Furthermore, we show that this epoxide is not rapidly metabolized in cultured cells. These results suggest that 24(S),25-epoxycholesterol may participate in the regulation of hepatic cholesterol metabolism in vivo.