ArticleJournal of lipid research2016
Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular β-glucosidases.
Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- Integrated Multi-Omics Analysis Uncovers Molecular Dysregulation in Glucosylceramide Synthase-Deficient Human Induced Pluripotent Stem Cells.Molecular & cellular proteomics : MCP · 2026Article
- Cerebrospinal fluid sphingolipid and sterol metabolite profiles of neurologically normal subjects.Molecular and cellular biochemistry · 2025Article
- Advances in mass spectrometry of lipids for the investigation of Niemann-pick type C disease.Lipids in health and disease · 2025Review
- Glucosylated cholesterol accumulates in atherosclerotic lesions and impacts macrophage immune response.Journal of lipid research · 2025Article
- Developing nanobodies as allosteric molecular chaperones of glucocerebrosidase function.Nature communications · 2025Article
- Cultured Macrophage Models for the Investigation of Lysosomal Glucocerebrosidase and Gaucher Disease.International journal of molecular sciences · 2025Article
- Synthesis and Biological Evaluation of Deoxycyclophellitols as Human Retaining β-Glucosidase Inhibitors.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model.JCI insight · 2024Article
- Nanoparticles for inducing Gaucher disease-like damage in cancer cells.Nature nanotechnology · 2024Article
- Hepatomegaly and Splenomegaly: An Approach to the Diagnosis of Lysosomal Storage Diseases.Journal of clinical medicine · 2024Review
- Animal Models for the Study of Gaucher Disease.International journal of molecular sciences · 2023Review
- New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases.International journal of molecular sciences · 2023Article
- The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines.Human molecular genetics · 2023Article
- Review
- Gangliosides and Cell Surface Ganglioside Metabolic Enzymes in the Nervous System.Advances in neurobiology · 2023Article
- a-Synuclein and lipids in erythrocytes of Gaucher disease carriers and patients before and after enzyme replacement therapy.PloS one · 2023Article
- Neuronal Ganglioside and Glycosphingolipid (GSL) Metabolism and Disease : Cascades of Secondary Metabolic Errors Can Generate Complex Pathologies (in LSDs).Advances in neurobiology · 2023Article
- Selective involvement of UGGT variant: UGGT2 in protecting mouse embryonic fibroblasts from saturated lipid-induced ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Juvenile mucopolysaccharidosis plus disease caused by a missense mutation in VPS33A.Human mutation · 2022Article
- Genotypic-Phenotypic Analysis, Metabolic Profiling and Clinical Correlations in Parkinson's Disease Patients from Tamil Nadu Population, India.Journal of molecular neuroscience : MN · 2022Article
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 5 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.