MSc Medical Biochemistry,
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
Lipids complexed to other compounds
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
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
The major glycolipids found in animal tissues are
They contain ceramide and one or more sugars.
Ceramide + Glucose ----- Glucocerebroside
Ceramide + Galactose ---Galactocerebroside
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.
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 ).
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
A specific ganglioside on intestinal mucosal cell binds to the
b subunit of the Cholera toxin when the a subunit enters the
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.
Sulpholipids or sulfatides
These are formed when sulfate groups are attached to
All these complex lipids are important components of
membranes of nervous tissue.
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
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
The lysosomal enzymes hydrolytically and irreversibly cleave
specific bonds in the glycosphingolipid.
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
Lipid storage diseases
They are called as spingolipidoses.
most common lysosomal storage diseases
enzyme deficiency – Beta glucosidase
lipid accumulating – Glucosylceramide
3 types – adult, infantile, juvenile
Hepatosplenomegaly, erosion of long bones, moderate
anemia, mental retardation in infants
Niemann- pick disease
enzyme deficiency – sphingomyelinase
lipid accumulating – sphingomyelin
severe CNS damage, mental retardation,
hepatosplenomegaly, cherry rod spot in macula
neurodegenerative course ( type A )
death occurs by 2 years of age
Globoid cell dystrophy
enzyme deficiency – Beta galactosidase
lipid accumulating – Galactosylceramide
severe mental retardation, total absence of myelin in CNS,
Globoid bodies in white matter
enzyme deficiency – arylsulfatase
lipid accumulating – 3-sulfogalactosylceramide
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 –
enzyme deficiency – alpha galactosidase
lipid accumulating – Globotriaosylceramide
progressive renal failure, death by 5 years of age, skin rash,
purplish papules appear, X – linked inheritance
enzyme deficiency – Hexosaminidase A
lipid accumulating – GM2 Ganglioside
Incidence 1 in 6000 births
mental retardation, blindness, cherry red spot in the macula,
muscular weakness, progressive deterioration, death by 3-4
enzyme deficiency – Beta-galactosidase
lipid accumulating – Ganglioside (GM1)
mental retardation, hepatosplenomegaly, skeletal
deformities, foam cells in bone marrow, cherry-red macula in
enzyme deficiency – Hexosaminidase A and B
lipid accumulating – Globoside
neurological deficit, mental retardation
enzyme deficiency – Ceramidase
lipid accumulating – ceramide
hoarseness, dermatitis, subcutaneous nodules of lipid-laden
cells, tissues show granulomas, skeletal deformation, painful
and progressive joint deformity, mental retardation, fatal in
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.
Shell-like inclusion bodies are seen in Tay-Sachs disease and
a wrinkled tissue paper appearance of the cytosol is seen in
All these diseases can be diagnosed prenatally by
amniocentesis and culture of amniotic fluid cells.
Lysosomal storage diseases are diagnosed by quantitative
Carriers are best diagnosed by DNA analysis of the common
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.
Gaucher disease has also been treated by bone marrow
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