CLINICAL CASES
255
Gangliosidoses: The build-up of gangliosides in the lysosome as a result of
the deficiency of one or more enzymes involved in the degradation of
gangliosides.
I-cell disease: A disease in which there is a buildup of a number of differ-
ent biomolecules that are normally degraded in the lysosome as a result
of a deficiency in an enzyme that modifies lysosomal enzymes so that
they are targeted to the lysosome.
Lysosomal storage disorders: Genetic diseases that are a result of a defi-
ciency of one or more enzymes present in the lysosome. This leads to a
buildup of the biomolecules that are normally degraded in the lysosome.
Sphingolipid: Any of a number of lipid molecules that contain sphingosine
as part of its molecular structure. These include ceramide, sphin-
gomyelin, cerebrosides, sulfatides, and gangliosides.
Tay-Sachs disease: A genetic disease that is a result of a deficiency in hex-
osaminidase A (P-A-acetylhexosaminidase), an enzyme that is involved
in the degradation of gangliosides in the lysosome. The disease is preva-
lent in Jewish children of Eastern European descent and leads to a
buildup of ganglioside GM2 in nerve cells of the brain and neuronal
dysfunction.
D ISC U SSIO N
Sphingolipids are a class of lipids found in biological membranes in which
the backbone of the lipid molecule is sphingosine, an 18-carbon amino
alcohol. This is in contrast to the glycerol backbone found in lipids such as
phospholipids. The precursor molecules for the synthesis of sphingosine are
palmitoyl-CoA and serine, which condense to form 3-dehydrosphinganine
(3-ketodihydrosphingosine; Figure 28-1). This is followed by a reduction reac-
tion using NADPH to form sphinganine (dihydrosphingosine). Ceramide is
formed in a two-step reaction by the formation of an amide bond between
sphinganine and a long-chain fatty acid (usually behenic acid, a saturated
C-22 fatty acid). This is followed by an oxidation reaction using FAD that
introduces a
trans-double
bond into the sphinganine backbone.
Ceramide is a building block for all other sphingolipids. Figure 28-2 shows
the synthesis of some of these sphingolipids from ceramide. The reaction of
phosphatidyl choline and ceramide (via esterification) yields sphingomyelin, a
phosphate-containing subclass of sphingolipids found in the nervous tissue of
higher animals. The addition of one or more sugar residues to ceramide yields
the glycosphingolipids. The glycosphingolipid cerebroside contains one residue
of glucose or galactose.
Gangliosides are complex carbohydrate-rich sphingolipids containing
three or more sugar residues esterified to ceramide with one of the sugars
being sialic acid (A-acetylneuraminic acid, or NANA). Gangliosides are syn-
thesized by the stepwise addition of nucleoside-activated sugar residues
to ceramide. Ganglioside nomenclature is a bit unusual. The ganglioside is
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