Biology Reference
In-Depth Information
by the reticuloendothelial (RES) system, primarily within the spleen. This mechanism is
responsible for removing one million old erythrocytes per second from the blood.
B. GLYCOLIPIDS
16]
).
The glycolipids include cerebrosides that have only one sugar attached (either glucose or
galactose), globosides that have either a di-, tri-, or tetra-saccharide attached, but do not
contain sialic acid and gangliosides that have complex oligosaccharides attached that
includes at least one sialic acid residue.
The name ganglioside was coined by E. Klenk in 1942 for lipids isolated from ganglion
cells of the brain. In fact gangliosides can amount to 6% of brain lipid weight where they
constitute 10
In animals the major glycolipids are sphingolipids (discussed in Chapter 5 and
[14
e
25% of the
membrane outer leaflet lipids). More than 60 gangliosides that differ in number and arrange-
ment of the sugars, particularly sialic acid, have now been identified. In the plasma
membrane outer leaflet, glycolipids accumulate into lipid rafts (see Chapter 8) and therefore
are involved in cell signaling. They serve as receptors of signaling proteins including inter-
feron, epidermal growth factor, nerve growth factor, and insulin. In addition, gangliosides
bind specifically to viruses and to various bacterial toxins, such as those from botulism,
tetanus, and cholera. It has been proposed that toxins utilize the gangliosides to hijack an
existing retrograde transport pathway from the plasma membrane to the endoplasmic retic-
ulum. Since binding to cholera toxin is the primary experimental marker used to identify
lipid rafts on the surface of plasma membranes, it may be through lipid rafts that these toxins
function. Due to information stored within the 'carbohydrate code' and important functions
of sialic acid, gangliosides are also intimately involved in complex cell
e
12% of the total
lipid content of neuronal membranes (20
e
cell recognition and
serve as essential antigens in immunology. Gangliosides are not found outside of the animal
kingdom.
Malfunctions in the enzymatic degradation of sphingosine-containing glycolipids, partic-
ularly the gangliosides, have been linked to a family of devastating, incurable genetic
diseases that are grouped together as lysosomal storage diseases (LSDs)
[17]
. These diseases
all result when a specific lytic enzyme is defective or missing, resulting in abnormal accumu-
lation of the enzyme's substrate in the lysosomal membrane. One series of these diseases
results from the failure to degrade the ganglioside: GM
1
/
e
GM
3
(
Figure 7.5
)
The best known disease involving failure to degrade a ganglioside (generally known as
gangliosidoses or sphingolipidoses) is Tay-Sachs Disease
[18]
. Tay-Sachs was the first gan-
gliosidosis identified (in 1881) and results from a genetic mutation that fails to produce the
enzyme hexoseaminidase A that normally would convert GM
2
/
GM
2
/
galactosamine
(
Figure 7.5
). As a result, GM
2
accumulates in the lysosomal membrane producing a plethora
of eventually fatal complications. In GM
2
, G stands for glycoside, M for mono (or one) sialic
acid and 2 indicates it is the second mono-sialo ganglioside ever characterized. Accumulation
of GM
2
occurs primarily in the lysosomes of tissues that are normally enriched in ganglio-
sides (neurons and brain) resulting in severe neurologic symptoms and death before age 5.
Symptoms include seizures, mental retardation, paralysis, blindness, extreme sensitivity
to noise and the appearance of an unusual cherry-red macular spot. The trait is carried by
GM
3
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