This document discusses glycolipids, which are lipids that contain one or more sugar molecules. Glycolipids are classified as glycosphingolipids, globosides, gangliosides, and sulfatides. Glycosphingolipids contain ceramide and one or more sugars. Gangliosides contain sialic acid and contribute to cell membrane structure and function. Genetic defects that prevent the breakdown of glycolipids cause lipid storage diseases like Gaucher's disease and Tay-Sachs disease, leading to lipid accumulation in tissues and associated symptoms. Laboratory tests can diagnose these conditions by measuring enzyme levels or examining tissues. Some lipid storage diseases can be treated through enzyme replacement therapy.

1. M.Prasad Naidu
MSc Medical Biochemistry,
Ph.D.Research Scholar

2.  The Lipids are a heterogeneous group of compounds which
are relatively insoluble in water, but freely soluble in
nonpolar organic solvents like benzene, chloroform, ether,
hot alcohol, acetone,etc.
 Lipids are classified based on their chemical nature

3.  Simple lipids
 Compound lipids
 Derived lipids
 Lipids complexed to other compounds

4.  Compound lipids are esters of fatty acids containing groups
in addition to an alcohol and a fatty acid.
 Compound lipids are phospholipids, glycolipids and other
complex lipids.

5. Glycolipids
 Glycolipids are widely distributed in every tissue of the body,
particularly in nervous tissue such as brain.
 They occur particularly in the outer leaflet of the plasma
membrane, where they contribute to cell surface
carbohydrates.

6.  The major glycolipids found in animal tissues are
glycosphingolipids.
 They contain ceramide and one or more sugars.
 Ceramide + Glucose ----- Glucocerebroside
 Ceramide + Galactose ---Galactocerebroside

7. Globosides ( ceramide oligosaccharides )
 They contain two or more hexoses or hexosamines, attached
to a ceramide molecule.
 Ceramide + Galactose + Glucose -- Lactosyl ceramide
 Lactosyl ceramide is a component of erythrocyte membrane.

8. Gangliosides
 They are formed when ceramide oligo-saccharides have at
least one molecule of NANA ( N-acetyl neuraminic acid ) (
Sialic acid) attached to them.
 Ceramide – Glucose – galactose – NANA ; this is designated
as GM3 ( ganglioside M3 ).

9.  Gangliosides contribute to stability of paranodal junctions
and ion channel clusters in myelinated nerve fibres.
 Autoantibodies to GM1 disrupt lipid rafts, paranodal or nodal
structures, and ion channel clusters in peripheral motor
nerves.

10.  A specific ganglioside on intestinal mucosal cell binds to the
b subunit of the Cholera toxin when the a subunit enters the
cell.
 It keeps the level of cellular cAMP raised by inhibition of
GTPase activity of the G protein.
 Gangliosides also act as receptors for other toxins like tetanus
toxin, and toxins of viral pathogens.

11. Sulpholipids or sulfatides
 These are formed when sulfate groups are attached to
ceramide oligosaccharides.
Sulphated Cerebrosides
Sulphated globosides
Sulphated Gangliosides
 All these complex lipids are important components of
membranes of nervous tissue.

12. Synthesis of Glycosphingolipids
 synthesis of glycosphingolipids occurs primarily in the Golgi
apparatus by sequential addition of glycosyl monomers
transferred from UDP-sugar donors to the acceptor
molecule.

16. Degeneration of Glycosphingolipids
 Glycosphingolipids are internalized by endocytosis.
 All of the enzymes required for the degrative process are
present in lysosomes, which fuse with the endocytotic
vesicles.
 The lysosomal enzymes hydrolytically and irreversibly cleave
specific bonds in the glycosphingolipid.

17.  Failure of degradation of these compounds results in
accumulation of these complex lipids in CNS.
 This group of inborn errors is known as lipid storage
diseases.

18. Lipid storage diseases
 They are called as spingolipidoses.
Gaucher’s disease
 most common lysosomal storage diseases
 enzyme deficiency – Beta glucosidase

19.  lipid accumulating – Glucosylceramide
 Clincal symptoms
3 types – adult, infantile, juvenile
Hepatosplenomegaly, erosion of long bones, moderate
anemia, mental retardation in infants

20. Niemann- pick disease
 enzyme deficiency – sphingomyelinase
 lipid accumulating – sphingomyelin
 Clinical symptoms
severe CNS damage, mental retardation,
hepatosplenomegaly, cherry rod spot in macula
neurodegenerative course ( type A )
death occurs by 2 years of age

21. Krabbe’s disease
 Globoid cell dystrophy
 enzyme deficiency – Beta galactosidase
 lipid accumulating – Galactosylceramide
 Clinical symptoms
severe mental retardation, total absence of myelin in CNS,
Globoid bodies in white matter

22. Metachromatic leukodystrophy
 enzyme deficiency – arylsulfatase
 lipid accumulating – 3-sulfogalactosylceramide
 Clinical symptoms
Mental retardation and psychologic disturbances in adults,
demyelination, neurological deficit, difficulty in speech and
optic atrophy, progressive paralysis, dementia in adult form,
nerves stain yellowish-brown with cresyl violet –
metachromasia

23. Fabry’s disease
 enzyme deficiency – alpha galactosidase
 lipid accumulating – Globotriaosylceramide
 Clinical symptoms
progressive renal failure, death by 5 years of age, skin rash,
purplish papules appear, X – linked inheritance

24. Tay-Sachs disease
 enzyme deficiency – Hexosaminidase A
 lipid accumulating – GM2 Ganglioside
 Clinical symptoms
Incidence 1 in 6000 births
mental retardation, blindness, cherry red spot in the macula,
muscular weakness, progressive deterioration, death by 3-4
years

25. Generalized gangliosidoses
 enzyme deficiency – Beta-galactosidase
 lipid accumulating – Ganglioside (GM1)
 Clinical symptoms
mental retardation, hepatosplenomegaly, skeletal
deformities, foam cells in bone marrow, cherry-red macula in
the retina

26. Lactosyl ceramidoses
 enzyme deficiency – Beta-galactosidase
 lipid accumulating – Lactosyl ceramide
 Clinical symptoms
mainly CNS and reticulo-endothelial system affected

27. Sandhoff’s disease
 enzyme deficiency – Hexosaminidase A and B
 lipid accumulating – Globoside
 Clinical symptoms
neurological deficit, mental retardation

28. Farber disease
 enzyme deficiency – Ceramidase
 lipid accumulating – ceramide
 Clinical symptoms
hoarseness, dermatitis, subcutaneous nodules of lipid-laden
cells, tissues show granulomas, skeletal deformation, painful
and progressive joint deformity, mental retardation, fatal in
early life

30. Laboratory diagnosis
 A specific sphingolipidosis can be diagnosed by measuring
enzyme activity in cultured fibroblasts or peripheral
leukocytes, or by analysis of DNA.
 Histologic examination of the affected tissue is also useful.

33.  Shell-like inclusion bodies are seen in Tay-Sachs disease and
a wrinkled tissue paper appearance of the cytosol is seen in
Gaucher disease.
 All these diseases can be diagnosed prenatally by
amniocentesis and culture of amniotic fluid cells.

34.  Lysosomal storage diseases are diagnosed by quantitative
enzyme assay.
 Carriers are best diagnosed by DNA analysis of the common
mutations.

35. Treatment
 Replacement of deficient enzyme has been tried in Gaucher’s
disease, with limited success.
 Gaucher disease and Fabry disease are treated by
recombinant human enzyme replacement therapy, but the
monetary cost is extremely high.

36.  Gaucher disease has also been treated by bone marrow
transplantation.
 Other promising approaches are substrate deprivation
therapy to inhibit the synthesis of sphingolipids and
chemical chaperone therapy.
 Gene therapy for lysosomal disorders is also currently under
investigation.

37. thank you