By: Richard D. Cummings
Cholesterol can be glycosylated, and indeed glucosylated cholesterol is common (1). In animal cells, it is a β-D-glucopyranoside derivative of cholesterol (GlcChol), which is generated through a ‘transglycosylation’ pathway in the lysosomes, by the enzymes glucocerebrosidase (GBA) and GBA2 that use Glc-Ceramide (Glc-Cer) as a donor. The pathway occurs both within and outside of the lysosome, and under normal conditions GBA2, a cytosol-facing enzyme, generates GlcChol (2). In abnormal conditions, GlcChol levels rise in Gaucher disease patients that accumulate Glc-Cer and in patients with Niemann-Pick type C disease, in which cholesterol accumulates (1).
Regarding glucosyl-cholesterol, Helicobacter pylori in the intestine requires cholesterol for its lipid rafts, but cannot synthesize cholesterol (3); it acquires it from mammalian cells by first glucosylating mammalian membrane cholesterol with its α-glucosyltransferase to generate an β-D-glucopyranoside derivative of cholesterol (4). The glucose in the glucosyl-cholesterol is subsequently also acylated by enzymes of the bacterium.
References:
- Marques, A. R., Mirzaian, M., Akiyama, H., Wisse, P., Ferraz, M. J., Gaspar, P., Ghauharali-van der Vlugt, K., Meijer, R., Giraldo, P., Alfonso, P., Irun, P., Dahl, M., Karlsson, S., Pavlova, E. V., Cox, T. M., Scheij, S., Verhoek, M., Ottenhoff, R., van Roomen, C. P., Pannu, N. S., van Eijk, M., Dekker, N., Boot, R. G., Overkleeft, H. S., Blommaart, E., Hirabayashi, Y., and Aerts, J. M. (2016) Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular beta-glucosidases. J Lipid Res 57, 451-463
- Marques, A. R., Aten, J., Ottenhoff, R., van Roomen, C. P., Herrera Moro, D., Claessen, N., Vinueza Veloz, M. F., Zhou, K., Lin, Z., Mirzaian, M., Boot, R. G., De Zeeuw, C. I., Overkleeft, H. S., Yildiz, Y., and Aerts, J. M. (2015) Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice. PLoS One 10, e0135889
- Jan, H. M., Chen, Y. C., Yang, T. C., Ong, L. L., Chang, C. C., Muthusamy, S., Abera, A. B., Wu, M. S., Gervay-Hague, J., Mong, K. T., and Lin, C. H. (2020) Cholesteryl alpha-D-glucoside 6-acyltransferase enhances the adhesion of Helicobacter pylori to gastric epithelium. Commun Biol 3, 120
- Hsu, C. Y., Yeh, J. Y., Chen, C. Y., Wu, H. Y., Chiang, M. H., Wu, C. L., Lin, H. J., Chiu, C. H., and Lai, C. H. (2021) Helicobacter pylori cholesterol-alpha-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells. Virulence 12, 2341-2351