GLYCOLIPIDS (GLYCOSPHINGOLIPIDS) ARE

IMPORTANT IN NERVE TISSUES & IN THE

CELL MEMBRANE

• Glycolipids are lipids with an attached

carbohydrate or carbohydrate chain.

• They 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 which form the glycocalyx
 Sphingophospholipids
• Sphingolipids, the second large class of membrane
lipids, have a polar head and two non-polar tails.

• They contain no glycerol.

• Sphingolipids serve in intracellular communication
as the antigenic determinations of the ABO blood
group.

• Sphingosine is an 18-Carbon monounsaturated

alcohol containing an amino group
 Sphingophospholipids
• The backbone of
sphingomyelin is the amino
alcohol sphingosine, rather
than glycerol
• A long-chain fatty acid (22-
26 C) is attached to the
amino group of
sphingosine through an
amide linkage, producing a
ceramide which can also
serve as a precursor of
glycolipids
Ceramide is sphingosine plus fatty acid
complex ..
• There are two subclasses of sphingolipids all
derivatives of ceramide but differing in their head
groups:

– Sphingomyelins

– Glycolipids (CERAMIDE SUGARS)

• Neutral (uncharged) glycolipids
–Cerebrocides (ONE sugar unit)
–Globocides
• Acidic (negatively charged) glycolipids
–Gangliosides
• Sphingomyelins contain phosphocholine or
phosphoethanolamines as their polar head group
and are therefore classified along with
glycerophospholipids as phospholipids

• When the alcohol group at carbon 1 of sphingosine

is, esterified to phosphorylcholine, sphingomyelin,
the ONLY significant sphingophospholipid in
humans, is produced

• Sphingomyelin is an important constituent of the

myelin of nerve fibers
CERAMIDE IS THE PARENT COMPOUND OF
SPHINGOPHOSPHOLIPIDS AND GLYCOLIPIDS
• Sphingomyelin, a sphingosine-based phospholipid,
is a major structural lipid in the membranes of
nerve tissue

• Sphingomyelin of the myelin sheath contains

predominant longer-chain fatty acids such as
lignoceric acid and nervonic acid (24 carbon)

• whereas gray matter of the brain has

sphingomyelin that contains primarily stearic
acid(18 carbon)
• Sphingomyelin is degraded by sphingomyelinase, a
lysosomal enzyme that hydrolytically removes
phosphorylcholine, leaving ceramide

• The ceramide is, in turn, cleaved by ceramidase

into sphingosine and a free fatty acid

• The ceramide and sphingosine released by the

degradation of sphingomyelin play a role as
intracellular messengers
• Glycolipids are molecules that contain both
carbohydrate and lipid components

• Like the phospholipid sphingomyelin, almost all

glycolipids are derivatives of ceramide in which a
long-chain fatty acid is attached to the amino
alcohol sphingosine

• They are, therefore, more precisely called

glycosphingolipids

• CERAMIDE IS THE PARENT COMPOUND OF

SPHINGOPHOSPHOLIPIDS AND GLYCOLIPIDS
FA + ALCOHOL[SPINGOSINE] +CARBOHYDRATE
WITH NITROGEN BASE

Example
Cerebrosides
Gangliosides
• Ceramides, then, are the precursors of both
phosphorylated and glycosylated sphingolipids

• Like the phospholipids, glycosphingolipids are

essential components of all membranes in the
body, but they are found in greatest amounts in
nerve tissue

• They are located in the outer leaflet of the plasma

membrane, where they interact with the
extracellular environment
• As such, they play a role in the regulation of
cellular interactions, growth, and development

• Glycosphingolipids are antigenic, and they have

been identified as a source of blood group
antigens, various embryonic antigens specific for
particular stages of fetal development, and some
tumor antigens

• The carbohydrate portion of a glycolipid is the

antigenic determinant
• They also serve as cell surface receptors for cholera
and tetanus toxins, as well as for certain viruses and
microbes

• When cells are transformed (that is, when they lose

control of cell division and growth), there is a
dramatic change in the glycosphingolipid
composition of the membrane

• Genetic disorders associated with an inability to

properly degrade the glycosphingolipids result in
intracellular accumulation of these compounds
 STRUCTURE OF GLYCOSPHINGOLIPIDS

• The glycosphingolipids differ from sphingomyelin

in that they do not contain phosphate,

• and the polar head function is provided by a

monosaccharide or oligosaccharide attached
directly to the ceramide by an O-glycosidic bond

• The number and types of carbohydrate moieties

present help determine the type of
glycosphingolipid
• Glycosphingolipids,(neutral, uncharged) which
occur largely in the outer face of plasma
membranes have head groups with one or more
sugars connected directly to the -OH at C-1 of the
ceramide moiety
• Cerebrosides have a single sugar linked to ceramide
• Those with galactose (galactocerebroside, Cer-Gal)
are characteristically found in the plasma
membranes of cells in neural tissue

• Galactosylceramide is a major glycosphingolipid of

brain and other nervous tissue, found in relatively
low amounts elsewhere

• It contains a number of characteristic C24 fatty

acids, eg, cerebronic acid
Ceramide is sphingosine plus fatty acid
complex ..
• Those with glucose (glucocerebroside, Cer-Glc)
serve primarily as an intermediate in the synthesis
and degradation of the more complex
glycosphingolipids

• Glucosylceramide is the predominant simple

glycosphingolipid of
• extraneural tissues,(such as liver, spleen, and bone
marrow ) also occurring in the brain in small
amounts
• Globosides are glycosphingolipids with two or
more sugars, usually D -glucose, D- galactose, or N-
acetyl-o-galactosamine (GalNAc)

• Cerebrosides and globosides are sometimes called

neutral glycolipids, as they have no charge at pH 7
• Gangliosides, the most complex sphingolipids have
oligosaccharides as their polar head groups
• and one or more residues of N-acetylneuraminic
acid (NANA),
• the principal sialic acid found in human tissues

• Acidic glycosphingolipids are negatively charged at

physiologic pH

• Sialic acid gives gangliosides the negative charge at

pH 7 and sulfate groups give the negative charge in
Sulfatides
• Gangliosides are found primarily in the ganglion
cells of the central nervous system, particularly at
the nerve endings

• They are derivatives of ceramide oligosaccharides,

and contain one or more molecules of NANA

• Gangliosides are of medical interest because several

lipid storage disorders involve the accumulation of
NANA-containing glycosphingolipids in cells
• The notation for these compounds is G (for
ganglioside), plus a subscript M, D, T, or Q to
indicate whether there is one (mono), two, three, or
four (quatro) molecules of NANA in the ganglioside,
respectively.
• (Thus, GM indicates a ganglioside with monosialic
acid residue. Numerical subscripts are also used to
indicate chromatographic movement of
gangliosides (e.g. GM1, GM2, GM3) )
• Additional numbers and letters in the subscript
designate the sequence of the carbohydrate
attached to the ceramide
• Gangliosides are primarily components of cell
surface membrane and constitute a significant
fraction (6%) of brain lipids.

• They have considerable physiological and medical

significance.

• Their complex carbohydrate head groups, which

extend beyond the surface of cell membranes, act as
specific receptors for certain pituitary glycoprotein
hormones that regulate a number of important
physiological functions.
• Gangliosides are also receptors for bacterial protein
toxins such as cholera toxins.

• Gangliosides such as GM1, GM2 and GM3 form

receptors for hormones.

• Gangliosides are specific determinants of cell

recognition. They probably are involved in
differentiation of tissues and carcinogenesis.
 Sulfatides:

• Sulfo glyco sphingolipids (sulfatides) are

cerebrosides that contain sulfated galactosyl
residues,
• and are therefore negatively charged at physiologic
pH

• Sulfatides are found predominantly in nerve tissue

and kidney
Summary of Components

• Ceramide = Sphingosine + Fatty acid.

• Sphingomyelin = Ceramide+Phosphorylcholine.
• Cerebroside= ceramide + monosaccharide
i. Galactocerebroside
ii. Glucocerebrocide
•Globocide = ceramide + oligosaccharide
•Ganglioside = Ceramide + Oligosaccharide
+NANA (glu + gal + sialic acid).
 Structural Lipids in Membranes

• The central architectural feature of biological

membranes is a double layer of lipids, which acts as
a barrier to the passage of polar molecules and ions

• Membrane Iipids are amphipathic i.e. one end of

the molecule is hydrophobic, the other hydrophilic

• Their hydrophobic interactions with each other and

their hydrophilic interactions with water direct their
packing into sheets called membrane bilayers
• There are five general types of membrane lipids:

– Glycerophospholipids, in which the hydrophobic

regions are composed of two fatty acids joined to
glycerol with a phosphate on the third -OH
–
– Galactolipids(sulfolipids), which also contain two
fatty acids esterified to glycerol, but a mono- or
disaccharide and a SO4, on the third -OH
– Ether lipids, in which two alkyl chains are ether-
linked to glycerol

– Sphingolipids, in which a single fatty acid is

joined to a fatty amine, sphingosine

– Sterols, compounds characterized by a rigid

system of four fused hydrocarbon rings
• The hydrophilic moieties in these amphipathic
compounds may be as simple as a single -OH group
at one end of the sterol ring system, or they may be
much more complex

• In glycerophospholipids and some sphingolipids, a

polar head phosphate group is joined to the
hydrophobic moiety by a phosphodiester linkage;
these are the phospholipids
• Other sphingolipids lack phosphate but have a
simple sugar or complex oligosaccharide at their
polar ends; these are the glycolipids

• Within these groups of membrane lipids, enormous

diversity results from various combinations of fatty
acid "tails" and polar "heads"
• Lipoproteins are complexes of proteins and lipids
held together by non-covalent bonds, e.g.

• chylomicrons,
• very low density lipoproteins,
• low density lipoproteins,
• high-density lipoproteins.
They contain high percentage of lipids and a low
percentage of proteins.
 Chylomicrons
Lipid with Very low density lipoprotein
prosthetic (VLDL)
group PROTEIN Low density lipoprotein (LDL)
High density lipoprotein (HDL)
 Example

Vitamin A
Fatty acids Steroids Cholesterol
and D