Chapter 11: Outline
Lipid Classes
Fatty Acids and Derivatives
Triacylglycerols
Wax Esters
Phospholipids
Sphingolipids
Isoprenoids
Lipoproteins
Membranes
Membrane Structure
Membrane Function
11-1
Lipids
General Types
O
eg. A fatty acid
Open chain:
OH
long nonpolar tail with a polar
head
D
C
saponifiable
B
A
Fused ring
based on the steroid ring skeleton
11-2
Lipid Classes
1.
2.
3.
4.
Fatty acids and their derivatives
Triacylglycerols
Wax esters
Phospholipids
phosphoglycerides and
sphingomyelin
5. Sphingolipids (not sphingomyelin)
6. Isoprenoids (based on isoprene
structure)
11-3
Fatty Acids
Lauric acid: a typical saturated fatty acid with
12 carbons in the chain (in salt form)
Fatty acid: 12-20 carbons, even # carbons, no
branching, nonpolar carbon chain, polar
COO- group (as anion).
O
H3C
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
C
CH2
O
Nonpolar hydrophobic tail
“Polar” hydrophilic head
11-4
Fatty Acids-2
An unsaturated fatty acid has one or more
carbon-carbon double bonds in the chain.
The first double bond is usually at the ninth
carbon. The double bonds are not
conjugated and are usually cis.
O
H
C C CH2 CH2 CH2 C
O
CH
CH2
CH CH2
2 CH2
H
CH2
CH2
CH2
CH2
CH3
2
Palmitoleic acid, salt form
Cis double bond results
in a bent chain and lower mp.
11-5
Fatty Acids-3
Stearic 18:0
CH3(CH2)16COOH
Palmitoleic 16:1D9
CH3(CH2)5CH=CH (CH2)7COOH
Linolenic
18:2D9,12
CH3(CH2)4CH=CHCH2CH=CH(CH2)7CO
Arachidonic 20:4D5,8,11,14
CH3(CH2)3(CH2CH=CH)4(CH2)3 COOH
11-6
Triacylglycerols
When all three alcohol groups of
glycerol form esters with fatty
acids a triacylglycerol (triglyceride)
is formed.
O
Glycerol
part
CH2O C R1
O
CH O C R2
O
CH2O C R3
Fatty acid
chains
11-7
Triacylglycerols-2
TAGs which are solids at room
temperature are rich in saturated acids
and are called fats.
TAGs which are liquids at room
temperature are rich in unsaturated
acids and are called oils.
e.g. oil seeds include peanut, corn,
safflower, palm, and soybean.
11-8
Triacylglycerols-3
Triacylglycerols store fatty acids as fats
in animal bodies. Complete oxidation
of a fat yields about 38.9 kJ/g while
carbohydrates yield about 17.2 kJ/g.
Before a fat can be oxidized, it must be
hydrolyzed to the acid anion and
glycerol.
Biologically this is done by lipases.
Chemically base hydrolysis is called
saponification.
11-9
Triacylglycerols-4
Saponification (soap making)
basic hydrolysis of fats
CH2OH
O
CH2O C R3
CH OH
O
3 NaOH
CH
OH
2
CH O C R3
O
+
O
CH2O C R3
3 NaO C R3
a soap, Na or K
salt of a fatty acid
11-10
Wax Esters
Waxes are typically esters of fatty acids
and fatty alcohols. They protect the
skin of plants and fur of animal etc.
Examples of waxes include carnuba,
from the leaves of the Brasilian wax
palm, and beeswax.
O
CH3 CH2 24C O CH2 29 CH3
11-11
Phospholipids
Have hydrophobic and hydrophilic
domains.
Structural components of membranes
Emulsifying agents
Suspended in water they spontaneously
rearrange into ordered structures
Hydrophobic group to center
Hydrophilic group to water (Next slide)
(Basis of membrane structure)
11-12
Phospholipids-2
11-13
Phosphoglycerides
When the third OH of glycerol is esterified to a
phosphoric acid or a phosphoric acid ester
instead of a carboxylic acid, a
phosphoacylglycerol results.
O
CH2O C
O
CH O C
O
CH2O P
O
Phosphatidic acid
R1
CH2O
R2
CH O
OH
CH2O
Phosphatidic ester
O
C R1
O
C R2
O
P OR
11-14
O
Phosphatidyl esters, egs.
O
CH2O C R1
O
CH O C R2
O
CH2O P OR
O
R=
+
CH2 CH2 NH3
phosphatidylethanolamine
CH2 CH2 N(CH3)3
phosphatidylcholine
(lecithin)
+
O
O
OH
CH2 CH CH2 O P O CH O C R3
O CH2 O C R4
O
diphosphatidylglycerol
(cardiolipin)
11-15
Sphingolipids
These lipids are based on sphingosine,
are found in plants and animals, and
are common in the nervous system.
CH CH CH2 12 CH3
CH OH
CH NH2
CH2OH
11-16
Sphingolipids-2
CH CH CH2 12 CH3 CH CH CH2 12 CH3
CH OH
O
CH NH C R1
CH2OH
A ceramide
N-acylsphingosine
CH OH
O
CH NH C R1
O
+
CH2O P O CH2CH2N (CH3)3
O
A sphingomyelin
11-17
Glycolipids
Glycolipids have a carbohydrate bound
to the alcohol of a lipid via a glycosidic
link. Frequently a glucose or galactose
is bound to the primary alcohol of a
ceramide. The compound is called a
cerebroside. These compounds are
found in the cell membranes of nerve
and brain cells.
Glycolipids have no phosphate.
See the next slide for an example
11-18
Glycolipids-2
CH2 CH CH CH CH CH2 12 CH3
O NH OH
CH2OH
CO
O
H
A
cerebroside
H
R1
OH H
HO
H
H OH
11-19
Glycolipids-3: Gangliosides
Sphingolipids with one or more sialic
residues are called gangliosodes.
Names include M, D, T (# residues) and
subscripts for number of sugars
attached to the ceramide.
11-20
Gangleoside GM2
CH2OH
HO
O
OH
NH
CO
CH3
O
H
CH3 C N
CH2OH
O
O O
O
OH
OH
OH
-
R
CH2OH
O O Sph
OH
O COO
R = CH OH
CH OH
CH2OH
11-21
Sphingolipid Storage Diseases
Disease
Sympt.
Sph. Lip
Enzyme
Tay-Sachs Blindness,
muscle
weakenss
Gaucher’s Liver and
spleen
enlarge, MR
Krabbe’s demyelation,
MR
Ganglioside b-hexoseGM2
aminidaseA
NiemanPick
Sphingomyelin
MR
Glucocerebroside
b-glucosidase
Galactocer- b-galactosebroside
idase
Sphingomyelinase
11-22
Isoprenoids
Isoprenoids contain a repeating fivecarbon unit know as isoprene.
They are synthesized from isopentenyl
pyrophosphate.
Isoprenoids consist of terpenes and
steroids.
O O
CH3
CH3
CH2 C CH CH2 CH2 C CH2CH2 O P O P O
O O
isoprene unit isopentenylpyrophosphate
11-23
Terpenes
Monoterpenes: 2 isoprene units
geraniol (in germaniums)
Sesquiterpenes: 3 isoprene units
farnesene (part of citronells oil)
Diterpenes: 4 isoprene units
phytol (a plant alcohol)
Tetraterpenes: 8 isoprene units
cartenoids (orange pigment in plants)
11-24
Terpenes-2
Some biomolelcule (mixed terpenoids)
have isoprenoid (isoprenyl)
components. Examples include
vitamin E, ubiquinone, vitamin K, and
some cytokinins (plant hormones).
Some proteins are prenylated (attached
to isopreniod groups).
11-25
Terpenes-3
geraniol
OH
farnesene
phytol
OH
b-carotene
11-26
Steroids
Steroid lipids are based on the ring system
shown below. The next slide shows some
examples of steroid sex hormones and of
cholesterol, a lipid very important in human
physiology.
17
12
13
11
16
D
C
1
10 9
14 15
2
8
B
A
3
7
5
6
4
11-27
Steroid Examples
CH3
CH CH2 CH2 CH2 CH(CH3)2
CH3
H
Cholesterol
CH3
OH
H
H
H
HO
CH3
CH3
H
C O
progesterone
CH3
O
CH3
CH3
O
testosterone
11-28
Cardiac Glycosides
Cardiac glycosides increase the force of
O
cardiac muscle contraction.
Digitoxin
From digitalis purpurea
CH3
O O
CH3
CH3
3
aglycone part
O
OH
glycone part
11-29
Lipoproteins
The term is most often used for
molecular complexes found in blood
plasma of humans.
Contain: neutral lipid core of cholesterol
esters and/or TAGs surrounded by a
layer of phospholopid, cholesterol, and
protein.
Classes: chylomycrons, VLDL, LDL, HDL
11-30
Lipoproteins-2
Chylomycrons: very large and very low
density; transport intestineadipose
VLDL: made in liver; transport lipids to
tissues; depleted one to LDLs.
LDL: carry cholesterol to tissues
HDL: made in liver; scavenge excess
cholesterol esters; “good cholesterol”
11-31
Atherosclerosis
Atheromas (plaque) impede blood flow.
Plaque: smooth muscle cells,
macrophages, cell debris
Macrophages fill with LDLs
Coronary artery disease a very common
consequence. High plasma
concentrations of LDLs correlate with
risk.
11-32
11.2 Membranes
Each type of cell has a unique
membrane composition with varying
percentages of lipids, proteins, and
some carbohydrates.
The currently accepted model of the
membrane is the fluid mosaic model of
a lipid bilayer.
Some examples follow on the next slide.
11-33
Composition of Some Membranes
Human
erythrocyte
Mouse liver
Mitochondrial (inner)
Spinach
lamellar
Protein % Lipid %
49
43
Carb. %
8
46
54
2-4
76
24
1-2
70
30
6
11-34
G Guidotti, Ann Rev Biochem, 41:731, 1972
Membrane Lipids
1. Fluidity
Lateral movement of phospholipids is
rapid. Flip-flop, from one side to
the other is rare.
Increasing percentage of unsaturated
fats leads to more fluidity.
See next slide.
11-35
A fluid membrane model
11-36
Membrane Lipids-2
2. Selective permeability
The hydrophobic nature of the
membrane makes it impenetrable to
the transport of ionic and polar
substances.
Membrane proteins regulate passage
of ionic and polar substances by
binding to the polar compound or by
providing a channel.
11-37
Membrane Lipids-3
3. Self-sealing capacity
A break in the membrane immediately
and spontaneously seals.
4. Asymmetry
Bulkier molecules occur more often in
the inner side of the membrane.
11-38
Membrane Proteins
Most membranes require proteins to
carry out their functions.
Integral proteins are embedded in and/or
extend through the membrane.
Peripheral proteins are bound to
membranes primarily through
interactions with integral proteins.
Figure 11.23
11-39
Red Blood Cell Proteins-1
The two major integral proteins of red
blood cells are glycophorin and anion
channel protein.
Glycophorin has 131 AA and is about
60% carbohydrate. Certain
oligsaccharides constitute the ABO
and MN blood up antigens and help to
classify blood for transfusion.
11-40
Red Blood Cell Proteins-2
Anion channel protein has two identical
929 AA subunits and plays an
important role in CO2 (HCO3 )
transport.
HCO3 diffuses through the ion channel
in exchange for chloride (chloride shift)
and thereby maintains the electrical
potential.
11-41
Red Blood Cell Proteins-3
Peripheral proteins (mainly spectrin,
ankyrin, and band 4) help preserve the
cells unique biconcave shape.
No hemoglobin molecule is more than
1 mm from the cell’s surface. This
allows for easy diffusion of oxygen.
11-42
Membrane Function
Membranes are involved in:
Transport of molecules and ions into and
out of cells and organelles.
Binding of hormones and other
biomolecules.
11-43
Membrane Transport-1
Major types of membrane transport are
illustrated below.
Fig 11.26
11-44
Membrane Transport-2
Passive transport (no direct energy
input)
Simple diffusion-molecules move
through a membrane down a
concentration gradient (toward lower
concentration).
Facilitated diffusion-molecules move
through protein channels in membrane.
11-45
Membrane Transport-3
Facilitated diffusion
Chemically or voltage-regulated
e. g. acetyl choline binds to a receptor;
Na+ rushes into the cell causing
depolarization which in turn opens a
voltage gated channel for Na+.
Repolarizaton begins when a voltage+
+
gated K channel opens and K leave
the cell.
11-46
Membrane Transport-4
Facilitated diffusion (cont.)
A carrier protein binds to a molecule.
The protein changes conformation and
releases the molecule into the cell.
This process speeds diffusion but
cannot cause a net increase in solute
concentration over diffusion limits.
11-47
Membrane Transport-5
Active transport
Primary-energy provided by ATP
+
+
e. g. the Na -K pump
Secondary-concentration gradients
generated by primary active transport
are used to move substances across
membranes.
e. g. Na+ gradient (Na+-K+ pump) used
to transport glucose in kidney
tubules.
11-48
Membrane Transport-6
Cystic fibrous is a result of a missing or
defective plasma membrane
glycoprotein called cystic fibrosis
transmembrane conductance regulator
(CFTR) which functions as a chloride
channel in epithelial cells.
In CF, chloride is retained in the cells,
thick mucous forms due to osmotic
uptake of water in the cells. Chronic
pulmonary problems and infections
result.
11-49
Membrane Receptors
The LDL receptor was discovered during
an investigation of familial
hypercholesterolemia.
When a cell needs cholesterol, it
synthesizes the receptor which
migrates to a coated region of the
membrane. The “captured” cholesterol
is absorbed by endocytosis. Failure to
make the receptor is the most common
problem encountered.
11-50