Karu K, Hornshaw M, Woffendin G, Bodin K, Hamberg M, Alvelius G, Sjövall J, Turton J, Wang Y, Griffiths WJ.
J Lipid Res. 2007 Apr;48(4):976-87.976-987
In humans, the brain accounts for about 20% of the body’s free cholesterol, most of which is synthesized de novo in brain. To maintain cholesterol balance throughout life, cholesterol becomes metabolized to 24S hydroxycholesterol, principally in neurons. In mouse, rat, and probably human, metabolism to 24S-hydroxycholesterol accounts for about 50% of cholesterol turnover; however, the route by which the remainder is turned over has yet to be elucidated. Here, we describe a novel liquid chromatography (LC) multistage fragmentation mass spectrometry (MSn) methodology for the identification, with high sensitivity (low pg), of cholesterol metabolites in rat brain. The methodology includes derivatization to enhance ionization, exact mass analysis at high resolution to identify potential metabolites, and LCMSn (n53) to allow their characterization. 24S-hydroxycholesterol was confirmed as a major oxysterol in rat brain, and other oxysterols identified for the first time in brain included 24,25-, 24,27-, 25,27-, 6,24,- 7a,25-, and 7a,27- dihydroxycholesterols. In addition, 3b-hydroxy-5-oxo-5,6- secocholestan-6-al and its aldol, two molecules linked to amyloidogenesis of proteins, were characterized in rat brain.
http://www.jlr.org/content/48/4/976.full.pdfThe School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
United States
