Lipids & Membranes

Drs.Immanuel Meliala,M.Si.,Apt.

Senin 05 Des 11 jam:07-08.40 R:104

Rabu 07 Des 11 jam :07-08.40 R:104
Jumat 09 Des 11 jam 09-10.40 R:104
Lipids are non-polar (hydrophobic) compounds,
soluble in organic solvents.
Most membrane lipids are amphipathic, having a
non-polar end and a polar end.
Fatty acids consist of a hydrocarbon chain with a
carboxylic acid at one end.
A 16-C fatty acid: CH3(CH2)14-COO-
Non-polar polar

A 16-C fatty acid with one cis double bond between

C atoms 9-10 may be represented as 16:1 cis 9.
 O
Double bonds in fatty 
  C
acids usually have the 4
3 1 O

2
cis configuration.
Most naturally fatty acid with a cis- 9
occurring fatty acids double bond
have an even number
of carbon atoms.
Some fatty acids and their common names:
14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid;
18:1 cis9  oleic acid
18:2 cis9,12  linoleic acid
18:3 cis9,12,15  -linonenic acid
20:4 cis5,8,11,14  arachidonic acid
20:5 cis5,8,11,14,17  eicosapentaenoic acid (an omega-3)
 O

  C
4
3 1 O
2

fatty acid with a cis- 9

double bond

There is free rotation about C-C bonds in the fatty acid

hydrocarbon, except where there is a double bond.
Each cis double bond causes a kink in the chain.
Rotation about other C-C bonds would permit a more
linear structure than shown, but there would be a kink.
 Glycerophospholipids
Glycerophospholipids
CH2OH
(phosphoglycerides), are common
constituents of cellular membranes. H C OH
They have a glycerol backbone.
CH2OH
Hydroxyls at C1 & C2 are esterified
to fatty acids. glycerol

An ester forms
when a hydroxyl Formation of an ester:
reacts with a
O O
carboxylic acid,
R'OH + HO-C-R" R'-O-C-R'' + H2O
with loss of H2O.
l
 Phosphatidate
O

O H2 C O C R2

R1 C O CH O

H2 C O P O

O
phosphatidate

In phosphatidate:
 fatty acids are esterified to hydroxyls on C1 & C2
 the C3 hydroxyl is esterified to Pi.
 O

O H2C O C R2

R1 C O CH O

H2C O P O X

O
glycerophospholipid

In most glycerophospholipids (phosphoglycerides),

Pi is in turn esterified to OH of a polar head group (X):
e.g., serine, choline, ethanolamine, glycerol, or inositol.
The 2 fatty acids tend to be non-identical. They may differ
in length and/or the presence/absence of double bonds.
 O

R O

R O O R

O O
 O

O H2 C O C R2

R1 C O CH O

H2 C O P O

O H

OH OH
H OH
OH H
phosphatidyl- H H
inositol
H OH

Phosphatidylinositol, with inositol as polar head

group, is one glycerophospholipid.
In addition to being a membrane lipid,
phosphatidylinositol has roles in cell signaling.
 O

O H 2C O C R2

R1 C O CH O CH3
+
H 2C O P O CH2 CH2 N CH3

O CH3

p h o sp h atid ylch o lin e

Phosphatidylcholine, with choline as polar head

group, is another glycerophospholipid.
It is a common membrane lipid.
 O

O H2C O C R2
Each glycerophospholipid
R1 C O CH O
includes
 a polar region: H2C O P O X
glycerol, carbonyl O O
of fatty acids, Pi, & the glycerophospholipid
polar head group (X)
 non-polar hydrocarbon
tails of fatty acids (R1, R2).
 OH OH
Sphingolipids are derivatives of
H
the lipid sphingosine, which has a H2C C CH
long hydrocarbon tail, and a polar
H3N+ CH
domain that includes an amino group.
HC
O

 
(CH2 )12
O P O
sphingosine CH3
O OH
H
H2C C CH Sphingosine may be reversibly
H3N+ CH
phosphorylated to produce the signal
molecule sphingosine-1-phosphate.
HC
Other derivatives of sphingosine are
(CH2 )12 commonly found as constituents of
sphingosine-1-P
CH3
biological membranes.
 OH OH
H
H2C C CH

The amino group of sphingosine can H3N+ CH

form an amide bond with a fatty acid HC

carboxyl, to yield a ceramide.
(CH2 )12
OH OH
sphingosine CH3
H
H2C C CH

NH CH

O C HC
In the more complex sphingolipids,
R (CH2 )12 a polar “head group" is esterified
ceramide
to the terminal hydroxyl of the
CH3
sphingosine moiety of the ceramide. 
 CH3 O
H2 H2 
+
H3C N C C O P O

Sphingomyelin has CH3 O OH

a phosphocholine or phosphocholine H
H2C C CH
phosphethanolamine
head group. sphingosine NH CH

Sphingomyelins are O C HC
common constituent fatty acid R (CH2 )12
of plasma membranes
Sphingomyelin CH3

Sphingomyelin, with a phosphocholine head group, is

similar in size and shape to the glycerophospholipid
phosphatidyl choline.
 CH2OH
A cerebroside is a OH O
sphingolipid H
O
OH
OH H
(ceramide) with a H H2C
H
C CH
H
monosaccharide
H OH
such as glucose or NH CH

galactose as polar O C HC
head group. R (CH2 )12
A ganglioside is a cerebroside with
-galactose head group CH3
ceramide with a polar
head group that is a complex oligosaccharide, including
the acidic sugar derivative sialic acid.
Cerebrosides and gangliosides, collectively called
glycosphingolipids, are commonly found in the outer
leaflet of the plasma membrane bilayer, with their sugar
chains extending out from the cell surface.
Amphipathic lipids in
association with water form
complexes in which polar
regions are in contact with
water and hydrophobic Bilayer Spherical Micelle
regions away from water.
Depending on the lipid, possible molecular arrangements:
 Various micelle structures. E.g., a spherical micelle is
a stable configuration for amphipathic lipids with a
conical shape, such as fatty acids.
 A bilayer. This is the most stable configuration for
amphipathic lipids with a cylindrical shape, such as
phospholipids.
Cholesterol, an
important constituent
of cell membranes,
has a rigid ring
system and a short HO
branched C holesterol
hydrocarbon tail.

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

PDB 1N83 cholesterol

 HO Cholesterol
C holesterol in membrane

Cholesterol inserts into bilayer membranes with its

hydroxyl group oriented toward the aqueous phase &
its hydrophobic ring system adjacent to fatty
acid chains of phospholipids.
The OH group of cholesterol forms hydrogen bonds
with polar phospholipid head groups.
 Cholesterol
in membrane

Interaction with the relatively rigid

cholesterol decreases the mobility of
hydrocarbon tails of phospholipids.
Lateral mobility of a lipid, within the plane of a
membrane, is depicted at right and in an animation.

L a te ra l M o b ility
 Flip-flop of lipids (from one half of
a bilayer to the other) is normally
very slow.

F lip F lo p

Flip-flop would require the polar head-group of a

lipid to traverse the hydrophobic core of the
membrane.
 peripheral
Membrane lipid
proteins may be anchor
classified as:
 peripheral
lipid bilayer
 integral
 having a Membrane
lipid anchor integral Proteins
Peripheral proteins are on the membrane surface.
They are water-soluble, with mostly hydrophilic surfaces.
Often peripheral proteins can be dislodged by conditions
that disrupt ionic & H-bond interactions, e.g., extraction
with solutions containing high concentrations of salts,
change of pH, and/or chelators that bind divalent cations.
 lipid
anchor O O C

H 3C (CH2)14 C S CH2 CH cysteine

residue
membrane NH
palmitate

Some proteins bind to membranes via a covalently

attached lipid anchor, that inserts into the bilayer.
A protein may link to the cytosolic surface of the plasma
membrane via a covalently attached fatty acid (e.g.,
palmitate or myristate) or an isoprenoid group.

Palmitate is usually attached via an ester linkage to the

thiol of a cysteine residue.
 peripheral
lipid
anchor

lipid bilayer

Membrane
integral Proteins

Integral proteins have domains that extend into the

hydrocarbon core of the membrane.
Often they span the bilayer.
Intramembrane domains have largely hydrophobic
surfaces, that interact with membrane lipids.
Lipid rafts:
 Complex sphingolipids tend to separate out from
glycerophospholipids & co-localize with cholesterol in
membrane microdomains called lipid rafts.
 Membrane fragments assumed to be lipid rafts are
found to be resistant to detergent solubilization,
which has facilitated their isolation & characterization.
 1. membran non rakit 2.lipid rakit 3.lipid protein
trans membran rakit terkait 4. non rakit protein
membran 5.glikosilasi modifikasi(pada glikoprotein
dari glikolipid) 6.GPI-protein berlabuh
7. kholesterol 8glikolipid
 Differences in molecular shape may contribute to a
tendency for sphingolipids to separate out from
glycerophospholipids in membrane microdomains.
• Sphingolipids usually lack double bonds in their
fatty acid chains.
• Glycerophospholipids often include at least one
fatty acid that is kinked, due to one or more double
bonds.
• See diagram (in article by J. Santini & coworkers).
 Lipid raft domains tend to be thicker than adjacent
membrane areas, in part because the saturated
hydrocarbon chains of sphingolipids are more extended.
 CH3 O
H2 H2 
+
H 3C N C C O P O

CH3 O OH
phosphocholine H
H2C C CH
sphingosine NH CH
HO
O C HC C holesterol
fatty acid R (CH2 )12
Sphingomyelin CH3

 Hydrogen bonding between the hydroxyl group of

cholesterol and the amide group of sphingomyelin
may in part account for the observed affinity of
cholesterol for sphingomyelin in raft domains.
 Proteins involved in cell signaling often associate
with lipid raft domains.
• Otherwise soluble signal proteins often assemble in
complexes at the cytosolic surface of the plasma
membrane in part via insertion of attached fatty acyl
or isoprenoid lipid anchors into raft domains.
• Integral proteins may concentrate in raft domains via
interactions with raft lipids or with other raft proteins.
• Some raft domains contain derivatives of
phosphatidylinositol that bind signal proteins with
pleckstrin homology domains.
 -helix
R-groups in magenta

In an -helix, amino acid R-groups protrude out from the

helically coiled polypeptide backbone.
The largely hydrophobic R-groups of a membrane-
spanning -helix contact the hydrophobic membrane core,
while the more polar peptide backbone is buried.
Colors: C N O R-group (H atoms not shown).
alanine (Ala, A) isoleucine (Ile, I) leucine (Leu, L) valine (Val, V)
H H H H

H3N+ C COO H3N+ C COO H3N+ C COO H3N+ C COO

CH3 CH CH3 CH2 CH CH3

CH2 CH CH3 CH3

CH3 CH3
amino acids: non-polar aliphatic R-groups

Particular amino acids tend to occur at different

positions relative to the surface or interior of the bilayer
in transmembrane segments of integral proteins.
Residues with aliphatic side-chains (leucine, isoleucine,
alanine, valine) predominate in the middle of the bilayer.
 tryptophan tyrosine
H H

H2N C COO H3N+ C COO

CH2 CH2

Tyrosine and
tryptophan are HN
common near the
membrane surface. OH

It has been suggested that the polar character of the

tryptophan amide group and the tyrosine hydroxyl, along
with their hydrophobic ring structures, suit them for
localization at the polar/apolar interface.
 lysine arginine
H H

H3N+ C COO H3N+ C COO

CH2 CH2

CH2 CH2

CH2 CH2

CH2 NH

 NH3 C NH2

NH2

Lysine & arginine are often at the lipid/water interface,

with the positively charged groups at the ends of their
aliphatic side chains extending toward the polar
membrane surface. 
 C

membrane

N C N

 If two transmembrane -helices are predicted, N & C

termini should be on the same side. The segment
between the -helices should be on the other side.
 Simplified helical wheel diagram of four
-helices lining the lumen of an ion channel.

A “helical
wheel” looks
down the axis
of an -helix,
projecting side-
chains onto a Polar amino acid R-group
plane. Non-polar amino acid R-group

An -helix lining a water-filled channel might have

polar amino acid R-groups facing the lumen, & non-polar
R-groups facing lipids or other hydrophobic -helices.
Such mixed polarity would prevent detection by a
hydropathy plot.
  polar R group,  non-polar R group

In a -sheet, amino acid R-groups alternately point above

& below the sheet.(lihat Food Chemistry by R.O.Fennema)
Much of porin primary structure consists of alternating
polar & non-polar amino acids.
• Polar residues face the aqueous lumen.
• Non-polar residues are in contact with membrane lipids.
Explore an example of a bacterial porin with Chime.
 ikatan hidrogen anti paralel (titik titik) antara kelompok
peptida NH dan CO pada untai berdekatan.Panah
menunjukkan arah rantai. Atom O bola merah, atom N bola
biru
 s

secara sederhana, struktur primer protein adalah urutan

asam amino penyusun protein yang disebutkan dari kiri
(N-terminal/NH3+) ke kanan (C-terminal/COO-). AA
bisa ditulis dalam singkatan 3 huruf atau 1 huruf.
 Pada bagian tertentu dari protein, terdapat susunan AA yang membentuk suatu
struktur yang reguler dengan sudut-sudut geometri tertentu. Ada dua struktur
sekunder utama yaitu alfa-helix dan beta-sheet. Struktur ini terjadi akibat adanya
ikatan hidrogen antar AA