Chapter 24 Lipids. Lipids Lipids: Lipids: a class of naturally occurring organic compounds which...

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Chapter 24 Lipids Lipids

Transcript of Chapter 24 Lipids. Lipids Lipids: Lipids: a class of naturally occurring organic compounds which...

Page 1: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Chapter 24

LipidsLipids

Page 2: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Lipids

Lipids:Lipids: a class of naturally occurring organic compounds which are:– insoluble in water, but soluble in organic

solvents

Lipids are generally put into three classes– Storage Lipids– Structural Lipids– Lipids as Signals, Cofactors, and Pigments

Page 3: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Lipids

Storage Lipids (80% of the mass of a fat cell)– Fatty acids

• Long chain alkane or alkene with carboxylic acid at one end.

– Triacylglycerols• Glycerol triester of three fatty acids

– Waxes• Fatty acid ester with long chain alcohol

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Lipids

Structural Lipids (5% to 10% of dry mass of most cells)– Phosphoacylglycerols (glycerophospholipids)– Galactolipids (glycolipids)– Sulfolipids– Sphingolipids– Cholesterol (and Bile acids)

Page 5: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Lipids

Signals, Cofactors, and Pigments– Steroid hormones – Lipid-soluble vitamins– Eicosanoids (not transported in the blood)

• Prostaglandins

• Thromboxanes

• Leukotrienes

Page 6: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Triglyceride

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

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Fatty 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

Page 8: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Fatty Acids COOHCOOH

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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Triglycerides

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

Page 10: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Triglycerides 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

Page 11: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Hydrogenation

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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Soaps

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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Soaps

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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Soaps

– 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-]2Ca

2+2Na++

+

A sodium soap(soluble in water as micelles)

Calcium salt of a fatty acid(insoluble in water)

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Complex 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

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Complex 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

Glycerol Sphingosine – amino alcohol

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Membranes 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)

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Fluid Mosaic Model

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Glycerophospholipids 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)

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Glycerophospholipids

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-

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Glycerophospholipids

HOHO

OHOH

OH

OH

NH3+

HOCH2CHCOO-

HOCH2CH2N(CH3)3

HOCH2CH2NH2

inositol phosphatidylinositol

Name and FormulaName of Glycerophospholipid

ethanolamine

+choline lecithin

cephalin

serine cephalin

More often phosphatidyl____________

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Glycerophospholipids

– a lecithin (phosphotidylcholine)a lecithin (phosphotidylcholine)

CH2

CH

CH2

O

O

O

O

O P OCH2CH2N(CH3)3

O

O-

+

palmitic acid

linolenic acid

glycerol

choline

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Sphingolipids Found in the coatings of nerve axons

(myelin)– contain the long-chain aminoalcohol,

sphingosine,

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

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Glycolipids 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

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Steroids

SteroidsSteroids:: a group of plant and animal lipids that have this tetracyclic ring structure

A B

C D

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Cholesterol Cholesterol is the most abundant steroid in

the human body– in plasma membranes in all animal cells– precursor of all steroid hormones and bile acids

HO

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Lipoproteins

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

Page 28: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Lipoproteins Schematic of a low-density lipoprotein

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Cholesterol 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

Page 30: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Cholesterol 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

Page 31: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Levels 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

Page 32: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Levels 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

Page 33: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Steroid 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

Page 34: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Steroid Hormones

Among the synthetic anabolic steroids are

O

H3C

H3C

MethandienoneO

CH3

H3CH3C

OHOH

CH3

MethenoloneO

H3C

H3C O

4-Androstene-3,17-dione

Page 35: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Steroid 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

Page 36: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Steroid 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)

Page 37: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Steroid 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

Page 38: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Bile 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

HO OH

HO NH

O

COO-

HO OH

HO NH

O

SO32-

Glycocholate(from glycine)

Taurocholate(from taurine)

Page 39: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Prostaglandins

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

Page 40: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Prostaglandins 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

Page 41: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

ProstaglandinsCOOH

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)

Page 42: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

COX 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

Page 43: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Thromboxanes 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

Page 44: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

Leukotrienes Leukotrienes are also synthesized from

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

the lungs … can cause asthma-like attacks– they are 100 times more potent than histamine– anti-asthma drugs inhibit leukotrienes synthesis

OH OHCOOH

Leukotriene B4

1512

20

Page 45: Chapter 24 Lipids. Lipids  Lipids:  Lipids: a class of naturally occurring organic compounds which are: –insoluble in water, but soluble in organic.

End End Chapter 20Chapter 20

Lipids