24-dehydro Cholesterol is an immediate precursor to cholesterol in the Bloch pathway of cholesterol biosynthesis. Structurally, it varies from cholesterol only by a single double bond at carbon 24 and has been used as cholesterol substitute in cellular membrane studies. [1] During brain development, 24-dehydro cholesterol transiently accumulates, composing up to 30% of total brain sterol, where it is poised to rapidly enrich membrane sterols. [2] However, defects in cholesterol synthesis can lead to a condition called, desmosterolosis, which results in an accumulation of excess 24-dehydro cholesterol. [3] 24-dehydro Cholesterol has been reported to activate liver X receptor-target genes in both the liver of cholesterol-free mice and in cholesterol-starved macrophage foam cells in atherosclerotic lesions.[4][5]
Reference:
[1]. Huster, D., Scheidt, H.A., Arnold, K., et al. Desmosterol may replace cholesterol in lipid membranes. Biophys. J. 88(3), 1838-1844 (2005).
[2]. Jansen, M., Wang, W., Greco, D., et al. What dictates the accumulation of desmosterol in the developing brain? FASEB J. 27(3), 865-870 (2013).
[3]. Clayton, P.T. Disorders of cholesterol biosynthesis. Arch. Dis. Child. 78(2), 185-189 (1998).
[4]. Heverin, M., Meaney, S., Brafman, A., et al. Studies on the cholesterol-free mouse: Strong activation of LXR-regulated hepatic genes when replacing cholesterol with desmosterol. Arterioscler. Thromb. Vasc. Biol. 27(10), 2191-2197 (2007).
[5]. Spann, N.J., Garmire, L.X., McDonald, J.G., et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 151(1), 138-152 (2012)