SULFOSPHINGOLIPIDS
They contain a hydrophobic ceramide moiety and a
hydrophilic moiety which consists of mono- or oligosaccharide unit bound to the
C-1 hydroxy group of the ceramide. Generally, the terminal galactose residue is
esterified with sulfate at carbon 3. Details on their structure and metabolism
may be found in the Farooqui's review (Adv Lipid Res 1981, 18, 159).
Three major sulfosphingolipids are known from mammalian tissues :
- cerebroside 3-sulfate or sulfatide is a sulfogalactosyl ceramide
- ceramide dihexosyl sulfate is a sulfolactosyl ceramide
- ceramide trihexosyl sulfate
This group (known also as cerebroside 3-sulfate) is mainly formed of 3-sulfate esters of galactosylcerebrosides (galactosyl-3-sulfate esters) and is found in mammalian tissues as the corresponding cerebroside group.
The first evidence for the
existence of sulfur containing lipids was given by Thudichum (1884) who isolated
this lipid from human brain and gave it the name sulfatide. The first complete
description of the structure was given by Blix (Z Physiol Chem 1933, 219, 82).
Sulfatide is a major
constituent of brain lipids and is found in trace amount in other tissues. It is
an essential glycosphingolipid in the peripheral as well as the central nervous
system, constituting 4-6 mole% of the total lipids in adult brain myelin.
Sulfatide is also found in kidney and
retina. About half the fatty acids are a-hydroxylated.
This compound is formed from a cerebroside molecule by a sulfotransferase
reaction with a donor nucleotide, 3'-phosphoadenosine-5'phosphosulfate. This
enzyme is very active during the myelinisation process but the turnover of the
sulfate group is extremely slow. Curiously, these
sulfatides are also found in tissues that are very active in sodium transport (kidney,
salt glands, gills).
Sulfatide mediates diverse biological processes including the regulation of cell
growth , protein trafficking, signal transduction, cell adhesion, neuronal
plasticity and morphogenesis (Ishizuka I, Prog Lipid Res 1997, 36, 245).
Experiments on mice lacking sulfotransferase demonstrated that sulfatide is
required for myelinisation and in preventing neuronal degenerescence,
abnormalities in paranodal junctions (Honke
K et al., PNAS 2002, 4227), and maintenance of ion channels (Ishibashi
T et al., J Neurosci 2002, 22, 6507).
CERAMIDE DIHEXOSYL SULFATE
A sulfatide with two hexose moieties (glucose and galactose) has
been isolated from human kidney (Martensson E, Acta Chem Scand 1963, 17, 1174).
Equimolar amounts of ceramide, glucose, galactose, and sulfate are found in the
molecule. The sulfate group is esterified, as in sulfatides, with carbon 3 of
the galactose moiety. The linkage between galactose and glucose is identical to
lactose (b-1-4).
Its fatty acid composition is similar to that of sulfatides.
CERAMIDE TRIHEXOSYL SULFATE
This sulfated lipid was discovered by Slomiany BL in hog gastric
mucosa (Biochim Biophys Acta 1974, 348, 388). The oligosaccharide group is composed of one galactose
and two glucose moieties. The sulfate group is esterified,
as in the other sulfosphingolipids, with carbon 3 of the galactose moiety. It
appears that the fatty acids are poorly hydroxylated.
CERAMIDE TETRAHEXOSYL SULFATE
A sulfoglycosphingolipid with an oligosaccharide chain
composed of four units was characterized as the major sulfoglycolipid of mouse
small intestine (Leffler H et al., J Biol Chem 1986, 361, 1440). Its
global formula may be written as follow :
-O3SO-3Gal1-3GalNAc1-4Gal1-4Glc1-1Cer
This sulfoglycolipid is enriched in epithelial cells of mouse small intestine where it constitutes at least 90% of the acidic glycolipids and 4-8% of the total glycosphingolipids.
