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Principles and Applications ofInorganic, Organic, and

Biological ChemistryDenniston, Topping, and Caret

4th edChapter 18

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Power Point to Accompany

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18.1 Lipids• Lipids- a collection of organic

molecules united by solubility in nonpolar solvents.

• Varying chemical composition

• Four main groups

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Main Groups1. Fatty acids

Saturated and unsaturated

2. Glycerides

Contain glycerol (HOCH2CHOHCH2OH)

3. Nonglycerides

Sphingolipids, steroids, waxes

4. Complex lipids

lipoproteins

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Lipid Functions• As an energy source, lipids provide 9

kcal of energy per gram.• Triglycerides provide energy storage in

adipocytes.• Phosphoglycerides, sphingolipids, and

steroids are part of cell membranes.• Steroid hormones are critical intercell

messengers.• Lipid soluble vitamins (A, E, D, E)• Provide shock absorption and

insulation.

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18.2 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

2

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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.

2

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Fatty Acids-3Stearic 18:0 (# of C and double

bonds)

CH3(CH2)16COOH

Palmitoleic 16:19 (9 position of double bond)

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

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Fatty Acid PropertiesMp increases with carbon number.

Mp of saturated acid is higher than an unsaturated acid of same carbon number.

cis double bond prevents good alignment of molecules in unsaturated fatty acids. Lowers mp relative to saturated or trans acid.

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Fatty Acid Reactions-1Esterification

R CO

OH OH R' O R'R CO

+ +H+

warm H2O

Acid Hydrolysis

R CO

OH OH R'O R'R CO

++H+

warmH2O

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Fatty Acid Reactions-2Saponification

R CO

ONa OH R'O R'R CO

++NaOH

Hydrogenation of Double Bonds

2 H2, Ni

CH3 CH2 C

O

OH16

CH2CH CH CH2 C

O

OHCH3 CH2 CH CH4 7

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Eicosanoids: Prostaglandins, etc.

Arichadonic acid (20 carbons) is the eichosanoid presursor.

COO-

arachadonic acidProstaglandins have hormonelike

activity.

In PGF2, PG stands for prostaglandin; F for a particular group with OH on C-9; and the 2 indicates two double bonds.

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Prostaglandin Function• Stimulation of smooth muscle

• Regulation of steroid biosynthesis

• Inhibition of gastric secretion

• Inhibition of hormone-sensitive lipases

• Inhibition of platelet aggregation

• Stimulation of platelet aggregation

• Regulation of nerve transmission

• Sensitization to pain

• Mediation of inflammatory response

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Aspirin and ProstaglandinsAspirin inhibits prostaglandin synthesis

by acylating cyclooxygenase, an enzyme necessary for prostaglandin synthesis.

arachadonic acid

PGH2

cyclooxygenase-NH2

+

cyclooxygenase-NH CO

CH3NH

O CO

CH3

COO-

OH

COO-

Acylated enzyme

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18.3 Glycerides: TriacylglycerolsWhen all three alcohol groups of glycerol

form esters with fatty acids a neutral triacylglycerol (triglyceride) is formed.

Triglycerides serve as energy storage in adipose cells.

CH2

CH

CH2

O

O

O CO

CO

CO

R1

R2

R3

Fatty acid chains

Glycerolpart

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PhosphoglyceridesHave 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

(Basis of membrane structure)

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Phosphoglycerides-2When 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

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Phosphatidyl esters, egs.

CH2

CH

CH2

O

O

O PO

CO

CO

R1

R2

OR

O

R=CH2CH2NH3

+

phosphatidylethanolamine

CH2CH2N(CH3)3+

phosphatidylcholine(lecithin)

Lecithin has a polar head and is amphipathic. It is the major phospholipid in pulmonary surfactant and an emulsifying agent.

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18.4 Nonglyceride Lipids: Sphingolipids

These 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

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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 sphingomyelinEssential to cerebral functionand nerve transmission.

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Glycolipids or GlycosphingolipidsFrequently 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.

OCH2OH

HH

OHH

OH

OH

HH

OCH CH CH2

CH3CHOH

CHNH

CH2 12

C O

R1A cerebroside

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Glycolipids-2: GangliosidesGangliosides have oligosaccharide

groups with one or more sialic acid (N-acetylnuraminic acid) residues attached. Names include M, D, T (# residues) and subscripts for number of sugars attached to the ceramide.

See the next slide for the structure of a ganglioside associated with Tay-Sachs an autosomal recessive disease resulting in neurological deterioration.

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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

Sph=ceramide

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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

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SteroidsSteroids are synthesized from the five

carbon isoprene unit and are part of a diverse collection of lipids called isoprenoids. They also fit into the terpene classification.

CH2 CCH3

CH CH2 CH2 CCH3

CH2CH2 O PO

O PO

OOOisoprene unit isopentenyl-

pyrophosphate

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Steroids-2Steroid 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

456

7

8

910

111213

14 15

16

17

A B

C D

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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

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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

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18.5 Complex Lipids

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

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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”

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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.

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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.

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18.6 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.

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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

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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.

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A fluid membrane model

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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.

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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.

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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.

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Membrane TransportThe cell membranes is responsible for the

controlled passage of molecules and ions into and out of cells and organelles.

Binding of hormones and other biomolecules.

With passive transport, there is net movement of solute to a region of lower concentration (diffusion)

With facilitated diffusion, a membrane protein (a permease) assists in diffusion. The process still requires no energy and is passive.

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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.

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OsmosisOsmosis is the net flow of water through

a semipermeable membrane (ie. Cell wall) from a region of low solute concentration to a region of high solute concentration.

Osmotic pressure is that which must be applied to prevent flow of water across the membrane.

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Osmosis, cont.If a cell has a higher osmotic

concentration than the surrounding fluid, it’s fluid is said to be hypertonic. Water flows into the cell and it may burst or hemolyze.

If a cell has a lower osmotic concen-tration than the surrounding fluid, it’s fluid is said to be hypotonic. Water flows out og the cell and it shrinks or crenates..

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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.

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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.

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Membrane Transport-5

Active transport

Primary-energy provided by ATP

e. g. the Na+-K+ pump (Next slide)

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.

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Sodium-Potassium Pump

Insert Fig 18.21

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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.

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The End

Lipids