Glucosylceramide and galactosylceramide, small glycosphingolipids with significant impact on health and disease

Abstract

Numerous clinical observations and exploitation of cellular and animal models indicate that glucosylceramide (GlcCer) and galactosylceramide (GalCer) are involved in many physiological and pathological phenomena. In many cases, the biological importance of these monohexosylcermides has been shown indirectly as the result of studies on enzymes involved in their synthesis and degradation. Under physiological conditions, GalCer plays a key role in the maintenance of proper structure and stability of myelin and differentiation of oligodendrocytes. On the other hand, GlcCer is necessary for the proper functions of epidermis. Such an important lysosomal storage disease as Gaucher disease and a neurodegenerative disorder as Parkinson’s disease are characterized by mutations in the GBA1 gene, decreased activity of lysosomal GBA1 glucosylceramidase and accumulation of GlcCer. In contrast, another lysosomal disease, Krabbe disease, is associated with mutations in the GALC gene, resulting in deficiency or decreased activity of lysosomal galactosylceramidase and accumulation of GalCer and galactosylsphingosine. Little is known about the role of both monohexosylceramides in tumor progression, however, numerous studies indicate that GlcCer and GalCer play important roles in the development of multidrug-resistance by cancer cells. It was shown that GlcCer is able to provoke immune reaction and acts as a self-antigen in Gaucher disease. On the other hand, GalCer was recognized as an important cellular receptor for HIV-1. Together, these two molecules are excellent examples of how slight differences in chemical composition and molecular conformation contribute to profound differences in their physicochemical properties and biological functions.

Rottlerin Stimulates Exosome/Microvesicle Release Via the Increase of Ceramide Levels Mediated by Ampk in an In Vitro Model of Intracellular Lipid Accumulation

“…Hexosylceramides, after endocytosis of plasma membrane fragments, are transported to the lysosome by the endocytic vesicular pathway. Glycosphingolipids are then degraded on the surface of intralysosomal vesicles [ 44 ]. In addition to the enzymes, essential components of the intra-lysosomal degradation of glycosphingolipids are the sphingolipid activator proteins, saposins A, B, C and D and GM2-activator protein [ 44 ].…”

High-throughput metabolomics reveals dysregulation of hydrophobic metabolomes in cancer cell lines by Eleusine indica

“…Cers can be also produced from the degradation of GlcCers by the enzyme glucocerebrosidase (GCase) 74 . It has been suggested that the intracellular pool of Cer affects the pro-proliferative and antiapoptotic effects of GlcCer, whereby an increase in the synthesis of GlcCer decreases the level of Cer in cells 75 . In this study, the level of Cer was generally increased in the R-S5-C1-H1-treated cancer cells compared to controls, whereas levels of SM and GlcCer were decreased following treatment.…”

Lipid Transporters Beam Signals from Cell Membranes

“…Using substitutions, the study determined the most important helices for glucosylceramide transport: TM1, TM2, and TM6, where GlcCer clusters in the membrane rafts [45]. GlcCer metabolism disruption has been linked to lysosomal storage diseases such as Gaucher disease and Parkinson's disease [46]. GlcCer also plays a role in multidrug-resistance of cancer cells [46,47].…”

“…GlcCer metabolism disruption has been linked to lysosomal storage diseases such as Gaucher disease and Parkinson's disease [46]. GlcCer also plays a role in multidrug-resistance of cancer cells [46,47].…”