Sphingo-glycolipids

 Glycolipids with ceramide (N-acyl fatty acid

derivative of sphingosine) backbone rather than the
glycerol moieties.

 The C3 of ceramide are esterified with

carbohydrates to form the head group.

 There are many classes of sphingo-glycolipids,

among which three categories are most important
in membrane system
Categories of Sphingo-glycolipids
1. Cerebrosides

2. Globosides

3. Gangliosides
 Cerebrosides
 It is a ceramide with single sugar residue at
the C3-hydroxyl group.

 The sugar residue of cerebrosides may be either

glucose or galactose

 Thus there are 2 categories of cerebrosides:

– Glucocerebrosides
– Galactocerebrosides
 Cerebrosides
 Lack the phosphate group and thus they do not
hold any charge (non-ionic).

 Abundantly found in the cell membranes of nerves

and muscles of animals.

 Nerve cell membranes are particularly rich in

galactocerebrosides whereas glucocerebrosides are
abundant in other tissues.
 cer
e
cere
 Globosides
 They are sphingo-glycolipids with more than
one sugar as the side chain of a ceramide.

 They are different from gangliosides since

they lack the sialic acid residues.

 The carbohydrate moieties are usually a

combination of N-Acetyl-galactosamine, D-
glucose or D-galactose.
 Gangliosides
 Membrane lipid with most complex structure.
 It is a glyco-sphingolipid with many carbohydrate
moieties
 One or more sialic acids linked on the sugar
chain.
 About 6% of brain lipids are gangliosides and
they are first isolated from the ganglion of brain
cells.
 Gangliosides are also abundant in the lipid
rafts of plasma membrane.
 Gangliosides
 Have considerable physiological and medical significance
in our body.

 Act as specific receptors for glycoprotein hormones in the

cells.

 Some gangliosides also serve as receptors for some

bacterial protein toxins.

 Eg. cholera toxin of Vibrio cholerae

 Heat-labile enterotoxin of E. coli

 Gangliosides
 Gangliosides also help in cell-cell recognition

 Hence, they have a significant role in growth and

differentiation of tissues and also in carcinogenesis.

 Tay-Sachs disease is a hereditary disorder caused

by the breakdown of gangliosides, leading to fatal
neurological deterioration in the early childhood.
3. STEROLS
 Sterols
 Sterols are the third major category of membrane
lipids.

 Usually present in the membrane of eukaryotic cells.

 Structurally sterols consist of four fused carbon rings

(A, B, C, D) and a hydrocarbon chain (alkyl side chain).
C D

A B
 Sterols
 Rings A, B and C are six carbon cyclohexane rings.

 The ring D is a five carbon cyclopetane ring.

 This fused ring structure is called the steroid nucleus.

 The steroid nucleus of all sterols is derived from a

cyclized derivative called
cyclopentanoperhydrophenanthrene/gonane.
 Sterols
 One of the peculiarities of this carbon infused
ring structure is that it does not allow C – C free
rotation even though they are in single bonds.

Sterols
 Cholesterol
 A membrane constituent needed in all cells.

 Bile acids used for intestinal fat uptake and nuclear

hormones are synthesized from cholesterol.

 Cholesterol is only synthesized in the liver

 Hence, all other tissues must receive cholesterol by

trafficking through blood in the form of lipoprotein
particles.
 Cholesterol
 Cholesterol constitutes about 30-40% of all
membrane lipids in animals.

 Similar to other membrane lipids, cholesterol is

also amphipathic.

 Single polar hydroxyl (-OH) ‘head’ and non-

polar hydrocarbon ‘tail’.
Cholesterol, an
important constituent of cell
membranes, has a rigid ring
system and a short branched
hydrocarbon tail.

HO
Cholesterol

Cholesterol is largely
hydrophobic.
But it has one polar group,
a hydroxyl, making it
amphipathic.

PDB 1N83 cholesterol

 Cholesterol
 The –OH group and hydrocarbon chain are attached
to the C3and C17 of the steroid nucleus respectively.

 Cholesterol can esterify with long chain fatty acids to

form cholesterol esters such as cholesteryl stearate.

chol
 Cholesterol

 In mammals, cholesterol also acts as the metabolic

precursor of steroid hormones such as testosterone.

 Cholesterol is generally absent in plant cell membrane.

 However other sterols do occur in plants.

 Sterols of plants are commonly known as phytosterols.

Cholesterol Is The Precursor For Nuclear
Hormones
 Sterols
 Stigmasterol is an important membrane sterol of
plant cells.

 Campesterol and sitosterol are other plant

membrane sterols.

 Sterols are also present in the membranes of fungi.

 Ergosterol is the most common fungal sterol.

 Sterol Biosynthesis
• Humans and other animals: Begins with acetyl-CoA
building blocks and ends with DMAPP and IPP.
-Dimethylallyl pyrophosphate (DMAPP) and isopentenyl
pyrophosphate (IPP).

• Mevalonate is decarboxylated to 5-carbon

molecules: isoprenoids (DMAPP and IPP-
cholesterol b.blocks

• DMAPP and IPP donate isoprene units, which are

assembled and modified to form terpenes and
isoprenoids (lipids e.g carotenoids).
 Sterol Biosynthesis
• In subsequent steps DMAPP and IPP join to form
geranyl pyrophosphate (GPP), farnesyl
pyrophosphate (FPP) then squalene which is
then folded into a set of rings to make lanosterol.

• Lanosterol is then converted into other steroids

(e.g cholesterol and ergosterol).
 Sterols
 In animals and fungi, lanosterol acts as the
precursor of sterols

 In plants, cycloartenol is considered as the sterol

precursor.

 Both Lanosterol and Cycloartenol are derived from

the cyclization of triterpenoid – squalene.
 Sterols
 Bacteria are unable to synthesize any of the
sterols

 Thus bacterial membranes are generally free

of sterols.

 However some bacteria can incorporate

exogenous sterols in to their membrane.
HO Cholesterol
Cholesterol in membrane

 Cholesterol inserts into bilayer membranes

 Hydroxyl group: oriented toward the aqueous phase
 Hydrophobic ring system: adjacent to fatty acid
chains of phospholipids.
 The OH group of cholesterol forms hydrogen bonds
with polar phospholipid head groups.
 Cholesterol
 Interaction with the relatively rigid cholesterol
decreases the mobility of hydrocarbon tails of
phospholipids.
 Cholesterol’s presence in a phospholipid membrane
interferes with close packing of fatty acid tails in the
crystalline state.
 Thus inhibits transition to the crystal state.
 Phospholipid membranes with a high concentration of
cholesterol have a fluidity intermediate between the
liquid crystal and crystal states.
2 strategies to avoid phase changes of
membrane lipids…
1. Cholesterol.
- In the absence of cholesterol, plasma membranes
would crystallize at physiological temperatures.

2. Phospholipids whose fatty acids have 1 or

more double bonds
- lower the melting point to below physiological
temperature.
4. Archaeabacterial Ether Lipids
 Archaeabacterial Ether Lipids
• Three major known groups of Archaebacteria:
– Methanogens, Halophiles, and Thermophiles.

• Methanogens: anaerobic bacteria that

produce methane.

• Halophiles: salt loving

• Thermophiles: acidic extreme temperatures

 Archaeabacterial Ether Lipids
 Archaebacteria differ from all other organisms
in cell membrane components

 Cell wall is followed by the cell membrane that

serves as a barrier between the cell and its
environment

 4 features make archae membranes distinct

from other organism
 1. Chirality of glycerol
 Bacteria and eukaryotes have D-glycerol as
phospholipid backbones in their membranes

 Archaeans have L-glycerol in theirs

 The enzymes involved in the synthesis of D

and L glycerol are different
 2. Isoprenoid chains
 In bacteria and eukaryotes, side chains are fatty
acids of 16-18 carbon atoms

 In archaebacteria, side chains in the phospholipids

are made of isoprene units of 20 carbon atoms

 Isoprene units are the building blocks of terpenes

 Common terpenes include carotenes, cholesterol

and estrogen
 3. Ether linkage
 In all organisms, ester linkages bonds glycerol
to the side chains

 In archaebacteria, isoprene side chains are

attached to glycerol by ether linkage
 4. Branching of side chains
 Isoprene units in archae bacteria are so flexible

 Form many side branches of the same chain

 The fatty acids of bacteria and eukaryotes do no

have these side branches

 Side branches have the ability to form carbon rings

 Branching of side chains
• This happens when one of the side branches curls
around and bonds with another atom down the chain

• Makes a ring of 5 carbon atoms

• This ring formation is common among species

surviving in high temperatures

• Ring formation contributes to the structural stability of

the membrane
 Lecture Summary
 Structures of membrane lipids:
1. Phospholipids
– Glycero-phospholipids (e.g cardiolipin & plasmalogen)
– Sphingo-phospholipids (e.g sphingomyelin)
2. Glycolipids
– Glycero-glycolips (e.g galactolipids & sulfolipids)
– Sphingo-glycolipids (cerebrosides, globosides &
gangliosides
3. Sterols
- Cholesterol, cholesterol esters
4. Archaebacterial Ether Lipids