GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:26724485

From GONUTS
Jump to: navigation, search
Citation

Marques, AR, Mirzaian, M, Akiyama, H, Wisse, P, Ferraz, MJ, Gaspar, P, Ghauharali-van der Vlugt, K, Meijer, R, Giraldo, P, Alfonso, P, Irún, P, Dahl, M, Karlsson, S, Pavlova, EV, Cox, TM, Scheij, S, Verhoek, M, Ottenhoff, R, van Roomen, CP, Pannu, NS, van Eijk, M, Dekker, N, Boot, RG, Overkleeft, HS, Blommaart, E, Hirabayashi, Y and Aerts, JM (2016) Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases. J. Lipid Res. 57:451-63

Abstract

The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, glucocerebrosidase (GBA) and GBA2, located in and outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA and GBA2 are able to catalyze in vitro the transfer of glucosyl-moieties from GlcCer to cholesterol, and vice versa. Furthermore, the natural occurrence of 1-O-cholesteryl-β-D-glucopyranoside (GlcChol) in mouse tissues and human plasma is demonstrated using LC-MS/MS and (13)C6-labeled GlcChol as internal standard. In cells, the inhibition of GBA increases GlcChol, whereas inhibition of GBA2 decreases glucosylated sterol. Similarly, in GBA2-deficient mice, GlcChol is reduced. Depletion of GlcCer by inhibition of GlcCer synthase decreases GlcChol in cells and likewise in plasma of inhibitor-treated Gaucher disease patients. In tissues of mice with Niemann-Pick type C disease, a condition characterized by intralysosomal accumulation of cholesterol, marked elevations in GlcChol occur as well. When lysosomal accumulation of cholesterol is induced in cultured cells, GlcChol is formed via lysosomal GBA. This illustrates that reversible transglucosylation reactions are highly dependent on local availability of suitable acceptors. In conclusion, mammalian tissues contain GlcChol formed by transglucosylation through β-glucosidases using GlcCer as donor. Our findings reveal a novel metabolic function for GlcCer.

Links

PubMed PMC4766994 Online version:10.1194/jlr.M064923

Keywords

Animals; COS Cells; Cercopithecus aethiops; Cholesterol/metabolism; Female; Gaucher Disease/metabolism; Glycosylation; Humans; Male; Mice; Niemann-Pick Diseases/metabolism; RAW 264.7 Cells; beta-Glucosidase/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GBA2

involved_in

GO:0030259: lipid glycosylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GBA2

involved_in

GO:0008203: cholesterol metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:GBA2

enables

GO:0046527: glucosyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:GBA2

enables

GO:0050295: steryl-beta-glucosidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GBA3

involved_in

GO:0006680: glucosylceramide catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GBA3

enables

GO:0004348: glucosylceramidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GLCM

involved_in

GO:0008203: cholesterol metabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GLCM

involved_in

GO:0030259: lipid glycosylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GLCM

enables

GO:0050295: steryl-beta-glucosidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:GLCM

enables

GO:0046527: glucosyltransferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.