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LipidsLipids

Chapter 26Chapter 26

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LipidsLipids

Lipids:Lipids: A heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties.• They are insoluble in water but soluble in aprotic

organic solvents, including diethyl ether, methylene chloride, and acetone.

Lipids include:• triglycerides, phospholipids, prostaglandins,

prostacyclins, and fat-soluble vitamins.• cholesterol, steroid hormones, and bile acids.

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TriglyceridesTriglycerides

Triglyceride:Triglyceride: An ester of glycerol with three fatty acids.

O

CH2OCR

CH2OCR''

R'COCH

O

O

1. NaOH, H2O

2. HCl, H2O CH2OH

CH2OH

HOCH

RCOOH

R'COOH

R''COOH

A triglyceride 1,2,3-Propanetriol(Glycerol, glycerin)

+

Fatty acids

Saponification

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Fatty AcidsFatty Acids

Fatty acid:Fatty acid: A carboxylic acid derived from hydrolysis of animal fats, vegetable oils, or membrane phospholipids.• Nearly all have an even number of carbon atoms, most

between 12 and 20, in an unbranched chain.• The three most abundant are palmitic (16:0), stearic

(18:0), and oleic acid (18:1), where the first number is the number of carbons and the second is the number of double bonds in the hydrocarbon chain.

• In most unsaturated fatty acids, the cis isomer predominates; the trans isomer is rare.

• Unsaturated fatty acids have lower melting points than their saturated counterparts; the greater the degree of unsaturation, the lower the melting point.

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Fatty AcidsFatty Acids

The most common fatty acids.

Unsaturated Fatty Acids

Saturated Fatty Acids

20:418:318:218:116:1

20:018:016:014:012:0

Carbon Atoms:Double Bonds

Melting Point(°C)

Common Name

-49-11-5161

7770635844

Arachidonic acidLinolenic acidLinoleic acidOleic acidPalmitoleic acid

Arachidic acidStearic acidPalmitic acidMyristic acidLauric acid

Higher mp

Lower mp

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TriglyceridesTriglycerides

Physical properties depend on the fatty acid components.• Melting point increases as the number of carbons in

its hydrocarbon chains increases and as the number of double bonds decreases.

• Oils: Triglycerides rich in unsaturated fatty acids are generally liquid at room.

• Fats: Triglycerides rich in saturated fatty acids are generally semisolids or solids at room temperature.

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TriglyceridesTriglycerides

• example:example: a triglyceride derived from one molecule each of palmitic acid, oleic acid, and stearic acid, the three most abundant fatty acids in the biological world.

CH2OC(CH2)14CH3

CH2OC(CH2)16CH3

CH3(CH2)7CH=CH(CH2)7COCH

O

O

O

oleate (18:1)

stearate (18:0)

palmitate (16:0)

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TriglyceridesTriglycerides

The lower melting points of triglycerides rich in unsaturated fatty acids are related to differences in their three-dimensional shape.• Hydrocarbon chains of saturated fatty acids can lie

parallel with strong dispersion forces between their chains; they pack into well-ordered, compact crystalline forms and melt above room temperature.

• Because of the cis configuration of the double bonds in unsaturated fatty acids, their hydrocarbon chains have a less ordered structure and dispersion forces between them are weaker; these triglycerides have melting points below room temperature.

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Soaps and DetergentsSoaps and Detergents

Natural soaps are prepared by boiling lard or other animal fat with NaOH, in a reaction called saponification (Latin, sapo, soap).

Sodium soaps

1,2,3-Propanetriol(Glycerol; Glycerin)

A triglyceride(a triester of glycerol)

+

saponification+CH

CH2OCR

CH2OCR

CHOH

CH2OH

CH2OH

RCO 3NaOH

3RCO- Na

+

O

O

O

O

COO-Na+

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Soaps and DetergentsSoaps and Detergents

Soaps clean by acting as emulsifying agents:• Their long hydrophobic hydrocarbon chains are

insoluble in water and tend to cluster in such a way as to minimize their contact with water.

• Their polar hydrophilic carboxylate groups, on the other hand, tend to remain in contact with the surrounding water molecules.

• Driven by these two forces, soap molecules spontaneously cluster into micelles.

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Soaps and DetergentsSoaps and Detergents

• A soap micelle: nonpolar (hydrophobic) hydrocarbon chains cluster in the inside and polar (hydrophilic) carboxylate groups lie on the surface.

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Soaps and DetergentsSoaps and Detergents

• micelle:micelle: A spherical arrangement of organic molecules in water clustered so that their hydrophobic parts are buried inside the sphere and their hydrophilic parts are on the surface of the sphere and in contact with water.

• when soap is mixed with water-insoluble grease, oil, and fats, the nonpolar parts of the soap micelles “dissolve” these nonpolar dirt molecules and they are carried away in the polar wash water.

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Soaps and DetergentsSoaps and Detergents

Soaps form water-insoluble salts when used in water containing Ca(II), Mg(II), and Fe(III) ions (hard waterhard water).

+

+

A sodium soap(soluble in water as micelles)

Calcium salt of a fatty acid(insoluble in water)

2CH3(CH2)1 4COO- Na

+Ca

2 +

[CH3 (CH2)14COO-]2 Ca

2+2Na

+

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Synthetic DetergentsSynthetic Detergents

The design criteria for a good detergent are:• a long hydrocarbon tail of 12 to 20 carbons.• a polar head group that does not form insoluble salts

with Ca(II), Mg(II), or Fe(III) ions.

The most widely used synthetic detergents are the linear alkylbenzenesulfonates (LAS).

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Synthetic DetergentsSynthetic Detergents

Also added to detergent preparations are:• foam stabilizers.• bleaches.• optical brighteners.

Dodecylbenzene

Sodium 4-dodecylbenzenesulfonate(an anionic detergent)

CH3(CH2 )10 CH2

CH3(CH2 )10 CH2 SO3-

Na+

1. H2SO4

2. NaOH

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ProstaglandinsProstaglandins

Prostaglandins:Prostaglandins: A family of compounds that have the 20-carbon skeleton of prostanoic acid.

23

45

67

89

20

10

11 1213

1415

1617

1819

1

Prostanoic acid

COOH

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Prostaglandins, originProstaglandins, origin

Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers.• One such polyunsaturated fatty acid is arachidonic

acid (notice the all cis configurations).

COOH

Arachidonic acid1514

89

11 12

6 5

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Prostaglandins, examplesProstaglandins, examples

• Among the prostaglandins synthesized biochemically from arachidonic acid are:

PGE2

11

9

15

15

9

11

PGF2

HO

COOH

HO H

COOH

HO

HOHO H

O

PGE2 generated in macrophages of the liver and lungs triggers the earliest phase of fever following any infection

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ProstaglandinsProstaglandins

Research on the involvement of PGs in reproductive physiology has produced several clinically useful derivatives.• (15S)-15-methyl-PGF2 is used as a therapeutic

abortifacient.

COOH

HO

HOHO CH3

15

9

11

(15S)-15-Methyl-PGF2

extra methyl groupat carbon-15

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ProstaglandinsProstaglandins

• The PGE1 analog, misoprostol, is used to prevent the ulceration associated with the use of aspirin.

1615

Misoprostol

PGE1

1516

COOCH3

HO

O

HO

CH3

HO HHO

OCOOH

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EicosanoidsEicosanoids

The prostaglandins are members of an even larger family of compounds called eicosanoidseicosanoids, all of which contain 20 carbons and are derived from polyunsaturated fatty acids.

O

OOH

COOHO

OH OH

H H

HOOC 5

Thromboxane A2(a potent vasoconstrictor)

1

67

9 8

1113

2014

Prostacyclin(a platelet aggregation inhibitor)

189

11 1413

2015 1512

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EicosanoidsEicosanoids

Leukotrienes are found primarily in white blood cells.• One function is constriction of smooth muscles,

especially those of the lungs.

S

HO

COOH

HN

NH

NH2

O

O

COOH

COOH

glycine

L-glutamic acidL-cysteine

20

14

11 9 76 5

1

Leukotriene C4 (LTC4)(a smooth muscle constrictor)

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SteroidsSteroids

Steroids:Steroids: A group of plant and animal lipids that have this tetracyclic ring structure.

The features common to the ring system of most naturally occurring steroids are illustrated next.

A B

C D

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SteroidsSteroids

• The fusion of rings is trans and each atom or group at a ring junction is axial.

• The pattern of atoms or groups along the ring junctions is nearly always trans-anti-trans-anti-trans.

• The steroid system is nearly flat and quite rigid.• Most have have axial methyl groups at C-10 and C-13.

HCH3

HH

CH3

H

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CholesterolCholesterol

H3C

HO

H3C

H H

H

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AndrogensAndrogens

Androgens - male sex hormones.

AndrosteroneTestosteroneO

HOH

H

H3C H

H

H3C H3C

H

HH3C

H

O

HO

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Synthetic Anabolic SteroidsSynthetic Anabolic Steroids

• A way to increase the testosterone concentration is to use a prohormone, which the body converts to testosterone; for example “andro”.

O

H3C H

H H

H3CHOCH3

O

H3CCH3 H

H3C OH

H H

H

O

H3C H

H3C

HH

O

O

H CH3

H3C OC(CH2)8CH3

H H

O

Methandrostenolone Methenolone

Nandrolone decanoate 4-Androstene-3,17-dione(andro)

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Available on the internet, dangerousAvailable on the internet, dangerous Generic Name: methandrostenolone

Danabol / Dianabol has always been one of the most popular anabolic steroids available. Danabol / Dianabol's popularity stems from it's almost immediate and very strong anabolic effects. 4-5 tablets a day is enough to give almost anybody dramatic results. It is usually stacked with deca durabolin and testosterone enanthate. Along with strong anabolic effects comes the usual androgen side effects, users often report an overall sense of well being. Danabol / Dianabol is a strong anabolic and androgenic product. It most often produced dramatic gains in size and strength. Danabol / Dianabol was also shown to increase endurance and glycogen retention.

The down side is that this drug is responsible for a number of side effects. It is an alpha alkylated 17 compound, which is quite toxic to the liver. Average dosages for Danabol / Dianabol have been in the range of 15mg to 30mg a day oral or 50mg to 100mg a week by injection. Regarded by many athletes as being one of the most effective oral steroids ever produced. It was not known as the "Breakfast of Champions" for nothing. Danabol / Dianabol is still one of the most effective strength and size building oral steroids probably second only to Anadrol 50 but it is not as harsh on the system as Anadrol 50 is.

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EstrogensEstrogens

Estrogens - female sex hormones.

Progesterone Estrone

H3C

H

HH3C

H

C=OH

O

CH3

O

HO

H

H

H

H3C

AndrosteroneTestosteroneO

HOH

H

H3C H

H

H3C H3C

H

HH3C

H

O

HO

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Synthetic EstrogensSynthetic Estrogens

Progesterone-like analogs are used in oral contraceptives.

"Nor" refers to the absence of a methyl group here. The methyl group is present in ethindrone

Norethindrone

H3C

H

HH

OH

HOC CH

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Glucorticoid HormonesGlucorticoid Hormones

• Synthesized in the adrenal cortex.• Regulate metabolism of carbohydrates.• Decrease inflammation.• Involved in the reaction to stress.

CortisolCortisone

C=O

CH2OH

O

OH

H

H3C H

H

H3CO HO

H3C

H

HH3C

H

C=OOH

O

CH2OH

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Mineralocorticoid HormonesMineralocorticoid Hormones

• Synthesized in the adrenal cortex.• Regulate blood pressure and volume by stimulating

the kidneys to absorb Na+, Cl-, and HCO3-.

Aldosterone

C=O

CH2OH

O

H

H3C H

H

CHO

OH

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Bile AcidsBile Acids

Synthesized in the liver, stored in the gallbladder, and secreted into the intestine where their function is emulsify dietary fats and aid in their absorption and digestion.

HO

H H

H

HOH

OH COOH

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Biosynthesis of SteroidsBiosynthesis of Steroids

The building block from which all carbon atoms of steroids are derived is the two carbon acetyl group of acetyl-CoAStage 1: synthesis of isopentenyl pyrophosphate from

three molecules of acetyl-CoA.

Stage 2: synthesis of cholesterol.

Stage 3: conversion of cholesterol to other steroids.

glucocorticoid hormones (e.g., cortisone)

mineralocorticoid hormones (e.g., aldosterone)

sex hormones (e.g., testosterone and estrone)

bile acids (e.g., cholic acid)

cholesterol

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Vitamin EVitamin E

Four isoprene units, joined head-to-tail, beginning hereand ending at the aromatic ring

OH

O

Vitamin E (-Tocopherol)

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PhospholipidsPhospholipids

Phospholipids are the second most abundant group of naturally occurring lipids.• They are found almost exclusively in plant and animal

membranes, which typically consist of 40% -50% phospholipids and 50% - 60% proteins.

• The most abundant phospholipids are esters of phosphatidic acid (glycerol esterified with two molecules of fatty acid and one of phosphoric acid).

• The three most abundant fatty acids in phosphatidic acids are palmitic acid (16:0), stearic acid (18:0), and oleic acid (18:1).

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Phosphatidic acids, an examplePhosphatidic acids, an example

A phosphatidic acid

• Further esterification with a low-molecular weight alcohol gives a phospholipid.

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PhospholipidsPhospholipids

• Among the most common of these low-molecular-weight alcohols are:

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Phospholipids, an examplePhospholipids, an example

A lecithin

In aqueous solution, phospholipids spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers.

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Biological MembranesBiological Membranes

Fluid mosaic model:Fluid mosaic model: A biological membrane consists of a phospholipid bilayer with proteins, carbohydrates, and other lipids embedded on the surface and in the bilayer.• fluidfluid: Signifies that the protein components of

membranes “float” in the bilayer and can move freely along the plane of the membrane.

• mosaicmosaic: Signifies that the various components of the membrane exist side by side, as discrete units rather than combining to form new molecules and ions.

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Biological MembranesBiological Membranes

• Fluid-mosaic modelFluid-mosaic model of a biological membrane showing the lipid bilayer and membrane proteins on the inner and outer surfaces of the membrane and penetrating the thickness of the membrane.

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Fat-Soluble VitaminsFat-Soluble Vitamins

Vitamins are divided into two broad classes on the basis of their solubility: • Those that are fat soluble, and hence classified as

lipids.• Those that are water soluble.

The fat-soluble vitamins include A, D, E, and K.

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Vitamin AVitamin A

• Occurs only in the animal world.• Found in the plant world in the form of a provitamin in

a group of pigments called carotenes.

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Vitamin AVitamin A

The best understood role of Vitamin A is its participation in the visual cycle in rod cells.• the active molecule is retinal (vitamin A aldehyde),

which forms an imine with an -NH2 group of the protein opsin to form the visual pigment called rhodopsin.

• the primary chemical event of vision in rod cells is absorption of light by rhodopsin followed by isomerization of the 11-cis double bond to the 11-trans configuration.

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Vitamin A and the Chemistry of VisionVitamin A and the Chemistry of Vision

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Vitamin DVitamin D

A group of structurally related compounds that play a role in the regulation of calcium and phosphorus metabolism.• The most abundant form in the circulatory system is

vitamin D3.

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Vitamin EVitamin E

Vitamin E is a group of compounds of similar structure, the most active of which is -tocopherol.

• In the body, vitamin E functions as an antioxidant; it traps peroxy radicals of the type HOO• and ROO• formed as a result of oxidation by O2 of unsaturated hydrocarbon chains in membrane phospholipids.

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Vitamin KVitamin K

The name of this vitamin comes from the German word Koagulation, signifying its important role in the blood-clotting process.