20 20-1 © 2003 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 7e...

2020

20-1© 2003 Thomson Learning, Inc.All rights reserved

General, Organic, and General, Organic, and Biochemistry, 7eBiochemistry, 7e

Bettelheim,Bettelheim,

Brown, and MarchBrown, and March

2020


Chapter 20Chapter 20

LipidsLipids

2020


LipidsLipids• Lipids:Lipids: a heterogeneous class of naturally

occurring organic compounds classified together on the basis of common solubility properties• insoluble in water, but soluble in organic solvents

including diethyl ether, dichloromethane, and acetone

• Lipids include• fatty acids, triacylglycerols, sphingolipids,

phosphoacylglycerols, and glycolipids • lipid-soluble vitamins• prostaglandins, leukotrienes, and thromboxanes• cholesterol, steroid hormones, and bile acids

2020


TriglycerideTriglyceride• Triglyceride:Triglyceride: an ester of glycerol with three fatty

acids

O

CH2OCR

CH2OCR''

R'COCH

OO

1. NaOH, H2O

2. HCl, H2O CH2OH

CH2OH

HOCH

RCOOH

R'COOH

R''COOH

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

+

Fatty acids

2020


Fatty AcidsFatty Acids• Fatty acid:Fatty acid: an unbranched-chain 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 acid (16:0),

stearic acid (18:0), and oleic acid (18:1)• 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

2020


Fatty AcidsFatty AcidsCOOH

COOH

COOH

Unsaturated Fatty Acids

Saturated Fatty Acids

20:418:3

18:218:116:1

20:018:016:014:012:0

Carbon Atoms/Double Bonds*

MeltingPoint(°C)

Common Name

-49-11

-5161

7770635844

Arachidonic acidLinolenic acidLinoleic acidOleic acidPalmitoleic acid

Arachidic acidStearic acidPalmitic acidMyristic acid

Lauric acid

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TriglyceridesTriglycerides• Physical properties depend on the fatty acid

components• melting point increases as the number of carbons in

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

• triglycerides rich in unsaturated fatty acids are generally liquid at room temperature and are called oilsoils

• triglycerides rich in saturated fatty acids are generally semisolids or solids at room temperature and are called fatsfats

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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 London 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 London dispersion forces between them are weaker; these triglycerides have melting points below room temperature

2020


HydrogenationHydrogenation• Hardening: reduction of some or all of the

carbon-carbon double bonds of an unsaturated triglyceride using H2/catalyst• in practice, the degree of hardening is carefully

controlled to produce fats of a desired consistency• the resulting fats are sold for kitchen use (Crisco, Spry,

Dexo, and others)• margarine and other butter substitutes are produced by

partial hydrogenation of polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils

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SoapsSoaps• Natural soaps are prepared by boiling lard or

other animal fat with NaOH, in a reaction called saponificationsaponification (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

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SoapsSoaps• Soaps clean by acting as emulsifying agents

• their long hydrophobic hydrocarbon chains cluster so as to minimize their contact with water

• their polar hydrophilic carboxylate groups remain in contact with the surrounding water molecules

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

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SoapsSoaps• soaps form water-insoluble salts when used in water

containing Ca(II), Mg(II), and Fe(III) ions (hard waterhard water)

2CH3(CH2)14COO- Na+ Ca2+

[CH3(CH2)14COO-]2Ca2+2Na++

+

A sodium soap(soluble in water as micelles)

Calcium salt of a fatty acid(insoluble in water)

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Complex LipidsComplex Lipids• Phospholipids

• contain an alcohol, two fatty acids, and a phosphate ester

• in glycerophospholipids, the alcohol is glycerol• in sphingolipids, the alcohol is sphingosine

• Glycolipids• complex lipids that contain a carbohydrate

2020


Complex LipidsComplex LipidsComplex Lipids

Phospholipids

GlycolipidsGlycerophospholipids Sphingolipids

G l y c e r o l

S p h i n g o s i n e S p h i n g o s i n e

Fatty acid

Fatty acid

PO4-alcohol

Fatty acid

Fatty acid

Glucose orGalactose

PO4-Choline

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MembranesMembranes• Complex lipids form the membranes around cells

and small structures within cells• In aqueous solution, complex lipids

spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers• polar head groups are in contact with the aqueous

environment• nonpolar tails are buried within the bilayer• the major force driving the formation of lipid bilayers is

hydrophobic interaction• the arrangement of hydrocarbon tails in the interior can

be rigid (if rich in saturated fatty acids) or fluid (if rich in unsaturated fatty acids)

2020


Fluid Mosaic ModelFluid Mosaic Model

2020


GlycerophospholipidsGlycerophospholipids• GlycerophospholipidsGlycerophospholipids are the second most

abundant group of naturally occurring lipids• they are also called phosphoglycerides• found almost exclusively in plant and animal

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

• the most abundant phosphoacylglycerols are derived from phosphatidic acid, a molecule in which glycerol is esterified with two molecules of fatty acid and one of phosphoric acid

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

2020


GlycerophospholipidsGlycerophospholipids• A phosphatidic acid

• the fatty acid on carbon 2 is always unsaturated• further esterification with a low-molecular-weight

alcohol gives a glycerophospholipid

CH2

CH

CH2-O-P-O-

O

O

O

Oglycerol

palmitic acid

oleic acid

O

O-

2020


GlycerophospholipidsGlycerophospholipids

HOHO

OHOH

OH

OH

NH3+

HOCH2CHCOO-

HOCH2CH2N(CH3)3

HOCH2CH2NH2

inositol phosphatidylinositol

Name and FormulaName of Glycerophospholipid

ethanolamine

+choline lecithin

cephalin

serine cephalin

2020


GlycerophospholipidsGlycerophospholipids• a lecithina lecithin

CH2

CH

CH2

O

O

O

O

O P OCH2CH2N(CH3)3

O

O-

+

palmitic acid

linolenic acid

glycerol

choline

2020


SphingolipidsSphingolipids• Found in the coatings of nerve axons (myelin)

• contain the long-chain aminoalcohol, sphingosine, from which this class of compounds in named

OH

(CH2)12CH3

HO

NH2

SphingosineOH

(CH2)12CH3

HO

NHCR

A ceramide(an N-acylsphingosine)

OPOCH2CH2N(CH3)3

(CH2)12CH3

HO

NHCR

A sphingomyelinO

O-+

O O

2020


GlycolipidsGlycolipids• GlycolipidGlycolipid:: a complex lipid that contains a

carbohydrate• the carbohydrate is either glucose or galactose• the cerebrosides are ceramide mono- or

oligosaccharides

O

(CH2)12CH3

HO

NHCR

O

H

HO

H

HO

H

HOH

H

OHO

a-glycosidic bond

a unit of -D-glucopyranose

a ceramide

2020


SteroidsSteroids• SteroidsSteroids:: a group of plant and animal lipids that

have this tetracyclic ring structure

A B

C D

2020


CholesterolCholesterol• Cholesterol is the most abundant steroid in the

human body, and also the most important• it is a component in plasma membranes in all animal

cells• it is the precursor of all steroid hormones and bile

acids

HO

2020


LipoproteinsLipoproteins• Cholesterol, along with fats, are transported by

lipoproteins

Lipoprotein

Composition (% dry weight)

ProteinsCholesteroland esters

Phospho-lipids

Tri-glycerides

High-densitylipoprotein (HDL)

Low-densitylipoprotein (LDL)

Very-low densitylipoprotein (VLDL)

Chylomicrons

33 30 29 8

25 50 21 4

10 22 18 50

1-2 8 7 84

2020


LipoproteinsLipoproteins• Schematic of a low-density lipoprotein

2020


Cholesterol TransportCholesterol Transport• transport of cholesterol from the liver starts with VLDL• VLDL is carried in the serum• as fat is removed, its density increases and it becomes

LDL; LDL stays in the plasma for about 2.5 days• LDL carries cholesterol to cells, where specific LDL

receptors bind it• after binding, LDL is taken into cells where enzymes

liberate free cholesterol and cholesteryl esters

2020


Cholesterol TransportCholesterol Transport• high-density lipoproteins (HDL) transport cholesterol

from peripheral tissues to the liver and also transfer cholesterol to LDL

• while in the serum, free cholesterol in HDL is converted to cholesteryl esters

• in the liver, HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell

• these esters are used for the synthesis of steroid hormones and bile acids

• after LDL has delivered its cholesteryl esters to liver cells, it reenters circulation

2020


Levels of LDL and HDLLevels of LDL and HDL• most of the cholesterol is carried by LDL• normal plasma levels are 175 mg/100 mL• if there are sufficient LDL receptors on the surface of

cells, LDL is removed from circulation and its concentration drops

• the number of LDL receptors is controlled by a feedback mechanism

• when the concentration of cholesterol inside cells is high, the synthesis of LDL receptors is suppressed

• in the disease called hypercholesterolemia, there are not enough LDL receptors and plasma levels of cholesterol may be as high as 680 mg/100 mL

2020


Levels of LDL and HDLLevels of LDL and HDL• these high levels of cholesterol can cause premature

atherosclerosis and heart attacks• in general, high LDL means high cholesterol content in

the plasma because LDL cannot get into cells• therefore, high LDL together with low HDL is a

symptom of faulty cholesterol transport and a warning of possible atherosclerosis

• the serum cholesterol level controls cholesterol synthesis in the liver

• when serum cholesterol is high, its synthesis in the liver is low, and vice versa

• the commonly used statin drugs inhibit the synthesis of cholesterol by blocking HMG-CoA reductase

2020


Steroid HormonesSteroid Hormones• Androgens:Androgens: male sex hormones

• synthesized in the testes• responsible for the development of male secondary sex

characteristics

AndrosteroneTestosteroneO

OH

H3C

H3C H3C

H3C

O

HO

2020


Steroid HormonesSteroid Hormones• Among the synthetic anabolic steroids are

O

H3C

H3C

MethandienoneO

CH3

H3CH3C

OHOH

CH3

MethenoloneO

H3C

H3C O

4-Androstene-3,17-dione

2020


Steroid HormonesSteroid Hormones• Estrogens:Estrogens: female sex hormones

• synthesized in the ovaries• responsible for the development of female secondary

sex characteristics and control of the menstrual cycle

H3C

H3C

C=O

O

CH3

OH

HO

H3C

Progesterone Estradiol

2020


Steroid HormonesSteroid Hormones• Progesterone-like analogs are used in oral

contraceptives

H3C

O

OHC CH

H3C

O

OHC CCH3

NH3C

CH3

"Nor" refers tothe absence of a methyl group here

Norethindrone

Mifepristone(RU486)

2020


Steroid HormonesSteroid Hormones• Glucorticoid hormonesGlucorticoid hormones

• synthesized in the adrenal cortex• regulate metabolism of carbohydrates• decrease inflammation• involved in the reaction to stress

Aldosterone

C=O

CH2OH

O

H

H3C H

H

CHO

OH

2020


Bile SaltsBile Salts• Bile saltsBile salts, the oxidation products of cholesterol

• synthesized in the liver, stored in the gallbladder, and secreted into the intestine where they emulsify dietary fats and aid in their absorption and digestion

HO OH

HO NH

O

COO-

HO OH

HO NH

O

SO32-

Glycocholate(from glycine)

Taurocholate(from taurine)

2020


ProstaglandinsProstaglandins• Prostaglandins:Prostaglandins: a family of compounds that have

the 20-carbon skeleton of prostanoic acid

COOH2

3

4

5

67

89

2011

1213

1415

1617

1819

1

10

2020


ProstaglandinsProstaglandins• 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

COOH

Arachidonic acid1514

89

11 12

6 5

2020


ProstaglandinsProstaglandinsCOOH

2O2

OOH

COOHO

O

OH

COOH

O

HO

COOH

OH

HO

HO15

9 9

11 11

Arachidonic acid

PGF2PGE2

PGG2

Aspirin and other NSAIDs inhibit this enzyme

15

9

11

9

11

15

15

cyclooxygenase (COX)

2020


COX EnzymesCOX Enzymes• The COX enzyme occurs in two forms• COX-1 catalyzes the normal physiological

production of prostaglandins• COX-2 is responsible for the production of

prostaglandins in inflammation• when a tissue is injured or damaged, special

inflammatory cells invade the injured tissue and interact with resident cells, for example, smooth muscle cells

• this interaction activates COX-2 and prostaglandins are synthesized

2020


ThromboxanesThromboxanes• Thromboxanes are also derived from arachidonic

acid• thromboxane A2 induces platelet aggregation and

vasoconstriction• aspirin and other NSAIDs inhibit the synthesis of

thromboxanes by inhibiting the COX enzyme

O

OOH

COOH

Thromboxane A2

189

11 201512

10

2020


LeukotrienesLeukotrienes• Leukotrienes are also synthesized from

arachidonic acid• they occur mainly in leukocytes• they produce muscle contractions, especially in the

lungs and thereby can cause asthma-like attacks• in this regard, they are 100 times more potent than

histamine• several recently-developed anti-asthma drugs inhibit

the synthesis of leukotrienesOH OH

COOH

Leukotriene B4

1512

20

2020


End End Chapter 20Chapter 20

LipidsLipids

20 20-1 © 2003 Thomson Learning, Inc. All rights reserved General, Organic, and Biochemistry, 7e...

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