Chemistry Reference
In-Depth Information
Turning back to CD1, its loading with glycolipid takes place in late endosomes
and lysosomes with the help of lipid transfer proteins including GM2-activator
proteins and saposins, which also act on eukaryotic GSLs. Saposins isolate indi-
vidual lipids from the membrane surroundings, thus making them more accessi-
ble to degradative enzymes (see Section 10.14) or to CD1 binding. Recent studies
confi rmed that CD1- associated self - glycolipid presentation triggers autoimmune
reactions to GSL autoantigens [8]. Moreover, the CD1 presentation of tumor-
associated GSLs links these compounds to T- cell - mediated immune responses [9] .
These examples illustrate that the profi le of GSLs is tied to diverse states, warrant-
ing a survey of this class of glycolipids.
10.5
Glycosphingolipids ( GSL s )
Glycosphingolipids are found primarily in the plasma membrane of all vertebrate
tissues, and they are particularly abundant in the nervous system (for further
information on functions in the nervous system, please see Chapter 30.5; for an
example of orchestration of synthesis of a distinct ganglioside and its receptor, a
lectin, please see Chapter 25.2). The simplest neutral GSL structures are the
monoglycosylceramides. The major glycolipid of mammalian brain, for example,
is galactosylceramide, constituting about 16% of total lipid in the brain (Table
10.1). In comparison, glucosylceramide is a major constituent of skin lipids, where
it is essential for lamellar body formation in the stratum corneum and to maintain
the water permeability barrier of the skin. Beyond that, glucosylceramide com-
prises the core of most glycolipid structures in mammals. It is synthesized on the
cytosolic face of the endoplasmic reticulum by a glucosylceramide synthase (UDP-
glucose : ceramide glucosyltransferase), which transfers the glucose moiety from
UDP-glucose to ceramide. Glucosylceramide is subsequently translocated to the
Golgi lumen, where its carbohydrate chain is elongated to more complex GSLs by
Golgi - localized glycosyltransferases. Galactosylceramide synthase (UDP - galac-
tose : ceramide galactosyltransferase) initiates the elaboration of the less abundant
galactosphingolipid core structures (Figure 10.2). For naming diglycosylceramides
it is common to use the designation of the disaccharide, for example, lactosyl-
ceramide for
- D - glucosyl - (1,1) - ceramide. It is the starting
point for the biosynthesis of GSLs with extended glycan complexity. The GSLs are
divided into two categories which now will be explained.
β
- D - galactosyl - (1,4) -
β
10.6
Complex Neutral GSL s
The glycan chains of these compounds do not carry a negative charge. It turned
out to be rather cumbersome to fi nd systematic names for GSLs with long oligo-
saccharide chains. Therefore, suitable trivial names were coined for frequently
