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.