Glucosylceramide glycosphingolipids

Figure 3 - Proposed structures of CMHS from C. guilhermei (I) galactosylceramide (II) glucosylceramide. Glycosphingolipids of higher trypanosomatids...

The glycosphingolipids (GSLs) are sugar-containing lipids built on a backbone of ceramide they include galactosyl- and glucosylceramide (cerebrosides) and the gangliosides. Their structures are described in Chapter 14. They are mainly located in the plasma membranes of cells. 

An HPLC method for neutral glycosphingolipids was first designed for the analysis of human plasma glycolipids (3), which consist primarily of glucosylceramide, lactosylceramide, globo-triaosylceramide and globotetraosylceramide (globoside). 

Although glucosylceramides are the predominant epidermal glycosphingolipids,8 various classes of glycosphingolipids such as acylglucosylceramides and gangliosides have been identified in epidermis and cultured keratinocytes. 

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

Eckford PD, Sharom FJ (2005) The reconstituted P-glycoprotein multidrug transporter is a flip-pase for glucosylceramide and other simple glycosphingolipids. Biochem J 389 517-526... 

Major categories of glycosphingolipid. The six basic cores of mammalian glucosylceramides, two types of mammalian galactosylceramide and the core of an insect/nematode a/thro-type glycosphingolipid are shown [7,17]... 

Bovine milk contains an enzyme, in soluble form, which catalyses the transfer of D-galactose from UDP-D-galactose to D-glucosylceramide. The synthesis of the product, lactosylceramide, was inhibited by the presence of a-lactalbumin. Lactosylceramide was also an effective acceptor of D-galactose, but neutral glycosphingolipids or gangliosides were very poor receptors. 

Glucosylceramide is known to be the precursor of all the major classes of glycosphingolipids in mammalian tissues, while its counterpart, galactosyl-ceramide (GL-lb or cerebroside) gives rise only to a small group of glycolipids. The metabolism of galactosylceramide is discussed later. 

The glycosphingolipids of plants tend to resemble those of animals in being largely derived from glucosylceramide, and their assembly does not add anything to the principles illustrated by their animal counterparts. Sialic acid again appears to be absent. Glycoglycerolipids are common. 

Human acid glucosylceramidase, or GBA (glucosidase, beta, acid), catalyzes the hydrolysis of glucosylceramide to glucose and ceramide. As such, it is responsible for the penultimate step in the turnover of glycosphingolipids, an important metabolic pathway malfunctioning of which is responsible for... 

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