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11-1
Chapter 11: OutlineLipid Classes
Fatty Acids and Derivatives
Triacylglycerols Wax Esters
PhospholipidsSphingolipids
Isoprenoids Lipoproteins
Membranes
Membrane Structure
Membrane Function
11-2
Lipids
General Types
Open chain:
long nonpolar tail with a polar head
saponifiable
Fused ring
based on the steroid ring skeleton
OH
Oeg. A fatty acid
A B
C D
11-3
Lipid Classes1. Fatty acids and their derivatives
2. Triacylglycerols
3. Wax esters
4. Phospholipids
phosphoglycerides and sphingomyelin
5. Sphingolipids (not sphingomyelin)
6. Isoprenoids (based on isoprene structure)
11-4
Fatty AcidsLauric 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).
CH3
CH2CH2
CH2CH2
CH2CH2
CH2CH2
CH2CH2
C
O
O
Nonpolar hydrophobic tail“Polar” hydrophilic head
11-5
Fatty Acids-2An 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.
C
O
OCH2CH2
C C
CH2
CH2
CH2
CH2
CH2
CH2
HH
CH2
CH2
CH2
CH2
CH3
Palmitoleic acid, salt form
Cis double bond results in a bent chain and lower mp.
11-6
Fatty Acids-3Stearic 18:0
CH3(CH2)16COOH
Palmitoleic 16:19
CH3(CH2)5CH=CH (CH2)7COOH
Linolenic 18:29,12
CH3(CH2)4CH=CHCH2CH=CH(CH2)7CO
Arachidonic 20:4,8,11,14
CH3(CH2)3(CH2CH=CH)4(CH2)3 COOH
11-7
Triacylglycerols
When all three alcohol groups of glycerol form esters with fatty acids a triacylglycerol (triglyceride) is formed.
CH2
CH
CH2
O
O
O CO
CO
CO
R1
R2
R3
Fatty acid chains
Glycerolpart
11-8
Triacylglycerols-2TAGs 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.
11-9
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.
11-10
Triacylglycerols-4Saponification (soap making)
basic hydrolysis of fats
CH2
CH
CH2
O
O
O CO
CO
CO
R3
R3
R3
3 NaOH
CH2
CH
CH2
OH
OH
OH
+
NaO CO
R3a soap, Na or Ksalt of a fatty acid
3
11-11
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.
CH3 CH2 C
O
O CH2 CH324 29
11-12
PhospholipidsHave 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)
11-13
Phospholipids-2
11-14
PhosphoglyceridesWhen the third OH of glycerol is esterified to a
phosphoric acid or a phosphoric acid ester instead of a carboxylic acid, a phosphoacylglycerol results.
CH2
CH
CH2
O
O
O PO
CO
CO
R1
R2
OH
O
Phosphatidic acidCH2
CH
CH2
O
O
O PO
CO
CO
R1
R2
OR
OPhosphatidic ester
11-15
Phosphatidyl esters, egs.
CH2
CH
CH2
O
O
O PO
CO
CO
R1
R2
OR
O
R=
CH2CH2NH3
+
phosphatidylethanolamine
CH2CH2N(CH3)3+
phosphatidylcholine(lecithin)
CH2CHOH
CH2O PO
OOCH
CH2
OOCO
CO
R3R4
diphosphatidylglycerol(cardiolipin)
11-16
SphingolipidsThese lipids are based on sphingosine,
are found in plants and animals, and are common in the nervous system.
CH CH CH2 CH3
CH OH
CH NH2
CH2OH
12
11-17
Sphingolipids-2
CH CH CH2 CH3
CH OH
CH NH
CH2OH
12
CO
R1
A ceramideN-acylsphingosine
CH CH CH2 CH3
CH OH
CH NH
CH2O
12
OR1
P OO
CO
CH2CH2N+(CH3)3
A sphingomyelin
11-18
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
11-19
Glycolipids-2
OCH2OH
HH
OHH
OH
OH
HH
OCH CH CH2
CH3CHOH
CHNH
CH2 12
C O
R1A cerebroside
11-20
Glycolipids-3: GangliosidesSphingolipids 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.
11-21
Gangleoside GM2
OCH2OH
O
O
OH
O
SphOCH2OH
OH
OH
OOCH2OH
OH
OH
NHC OCH3
OR
NH
OH
COO-C
O
CH3 R = CH OHCH OHCH2OH
11-22
Sphingolipid Storage Diseases
Disease Sympt. Sph. Lip Enzyme
Tay-Sachs Blindness,
muscle weakenss
Ganglioside
GM2
-hexose-
aminidaseA
Gaucher’s Liver and spleen enlarge, MR
Glucocer-
ebroside
-glucos-
idase
Krabbe’s demyelation,
MR
Galactocer-
ebroside
-galactos-
idase
Nieman-Pick
MR Sphingo-
myelin
Sphingomy-
elinase
11-23
Isoprenoids
Isoprenoids contain a repeating five-carbon unit know as isoprene.
They are synthesized from isopentenyl pyrophosphate.
Isoprenoids consist of terpenes and steroids.
CH2 CCH3
CH CH2 CH2 CCH3
CH2CH2 O PO
O PO
OOOisoprene unit isopentenyl-
pyrophosphate
11-24
TerpenesMonoterpenes: 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)
11-25
Terpenes-2Some 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).
11-26
Terpenes-3
OHgeraniol
farnesene
phytol
-carotene
OH
11-27
SteroidsSteroid 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.
12
3
45
67
8
910
1112
13
14 15
16
17
A B
C D
11-28
Steroid Examples
CH CH2 CH2CH2CH(CH3)2
OH
H
CH3 H
CH3
H H
H
CH3
Cholesterol
O
CH3
CH3
OH
testosterone
O
CH3
CH3
C
CH3
O
progesterone
11-29
Cardiac GlycosidesCardiac glycosides increase the force of
cardiac muscle contraction.
OCH3
OOH
O
O
CH3
CH3
3
aglycone part
glycone part
DigitoxinFrom digitalis purpurea
11-30
LipoproteinsThe 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
11-31
Lipoproteins-2Chylomycrons: very large and very low
density; transport intestineadipose
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”
11-32
AtherosclerosisAtheromas (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.
11-33
11.2 MembranesEach 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.
11-34
Composition of Some Membranes
Protein % Lipid % Carb. %
Human
erythrocyte
49 43 8
Mouse liver 46 54 2-4
Mitochon-
drial (inner)
76 24 1-2
Spinach
lamellar
70 30 6
G Guidotti, Ann Rev Biochem, 41:731, 1972
11-35
Membrane Lipids1. 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.
11-36
A fluid membrane model
11-37
Membrane Lipids-22. 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.
11-38
Membrane Lipids-33. 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.
11-39
Membrane ProteinsMost 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
11-40
Red Blood Cell Proteins-1The 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.
11-41
Red Blood Cell Proteins-2Anion 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.
11-42
Red Blood Cell Proteins-3Peripheral proteins (mainly spectrin,
ankyrin, and band 4) help preserve the cells unique biconcave shape.
No hemoglobin molecule is more than 1 m from the cell’s surface. This allows for easy diffusion of oxygen.
11-43
Membrane FunctionMembranes are involved in:
Transport of molecules and ions into and out of cells and organelles.
Binding of hormones and other biomolecules.
11-44
Membrane Transport-1Major types of membrane transport are
illustrated below.
Fig 11.26
11-45
Membrane Transport-2Passive 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.
11-46
Membrane Transport-3Facilitated 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.
11-47
Membrane Transport-4Facilitated 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.
11-48
Membrane Transport-5Active 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.
11-49
Membrane Transport-6Cystic 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.
11-50
Membrane ReceptorsThe 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.
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