Oral Sessions (Day1, Day2, Day3)
Oral Sessions
- Day 3, May 21（Fri.） 15:25-15:45 Room A (Zoom)
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3A-O11-1525 PDF
Discovery of a new sterol metabolic pathway in the brain using hydrophilic interaction chromatography/mass spectrometry
β-Glucocerebrosidase (GBA) is a key enzyme that cleaves the β-linked glucose residue of glucosylceramide (GlcCer) to generate ceramide. Previously, we reported that lysosomal GBA1 and non-lysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides found in diverse species. Impaired GBA1 and GBA2 function is associated with neurological disorders. How GBA1 and GBA2 regulate β-GlcChol metabolism in the brain is unknown.
In this study, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of the isolated brain sterylglycoside revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Hydrophilic interaction chromatography/mass spectrometry of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient medaka revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. This is the first report to demonstrate the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.