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Lipids & Membranes: Biochemistry of Metabolism
Lipids & Membranes: Biochemistry of Metabolism
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.
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
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
O H 2C O C R2
R1 C O CH O CH3
+
H 2C O P O CH2 CH2 N CH3
O CH3
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
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
Sphingomyelins are O C HC
common constituent fatty acid R (CH2 )12
of plasma membranes
Sphingomyelin CH3
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.
Membrane fluidity:
The interior of a lipid bilayer
is normally highly fluid. liquid crystal crystal
In the liquid crystal state, hydrocarbon chains of
phospholipids are disordered and in constant motion.
At lower temperature, a membrane containing a single
phospholipid type undergoes transition to a crystalline
state in which fatty acid tails are fully extended, packing
is highly ordered, & van der Waals interactions between
adjacent chains are maximal.
Kinks in fatty acid chains, due to cis double bonds,
interfere with packing in the crystalline state, and lower
the phase transition temperature.
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
O H2C O C R2
R1 C O CH O
H2C O P O
O H
1 6
OH OPO32
H OH
2 OH H 5
PIP2 H H
3 4
phosphatidylinositol-
H OPO32
4,5-bisphosphate
O H2C O C R2
R1 C O CH O
H2C O P O
O H
1 6
OH OH
phosphatidyl- H OH
inositol- 2
OPO3 2
H
5
3-phosphate H H
3 4
H OH
H 3C C CH CH 2 CH 2 C CH CH 2 CH 2 C CH CH 2 S P r o t e in
fa rn e s y l re s id u e lin k e d to p ro te in v ia c y s te in e S
lipid bilayer
Membrane
integral Proteins
CH3 O OH
phosphocholine H
H2C C CH
sphingosine NH CH
HO
O C HC C holesterol
fatty acid R (CH2 )12
Sphingomyelin CH3
CH3 CH3
amino acids: non-polar aliphatic R-groups
CH2 CH2
Tyrosine and
tryptophan are HN
common near the
membrane surface. OH
CH2 CH2
CH2 CH2
CH2 CH2
CH2 NH
NH3 C NH2
NH2
membrane
N C N
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