Lipids

Bettelheim, Brown, Campbell and Farrell

Chapter 21

Lipids

• 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

Functional Classification of Lipids

• Storage of energy in animals

• Membrane components– Lipid bilayer

• Messengers – Primary: Hormones– Secondary: mediate hormonal response

• prostaglandins, thromboxanes, etc.

Lipids

• Lipids include– fatty acids, triacylglycerols, sphingolipids,

phosphoacylglycerols, and glycolipids – lipid-soluble vitamins– prostaglandins, leukotrienes, and

thromboxanes– cholesterol, steroid hormones, and bile acids

Structural Classification of Lipids

• Simple Lipids – Fatty acids, waxes

• Complex Lipids– Multiple components

• Steroids

• Prostaglandins, Thromboxanes and Leukotrienes

Fatty Acids• Fatty acid:Fatty acid: an unbranched-chain carboxylic acid derived

from hydrolysis of animal fats, vegetable oils, or membrane phospholipids– Usually unbranched chain with 10-20 carbons– EVEN number of carbons– May be saturated or unsaturated (C=C)– Unsaturated generally have cis double bonds– Unsaturated fatty acids have lower melting points than their

saturated fatty acids– Most abundant are palmitic acid (16:0), stearic acid (18:0),

and oleic acid (18:1)

Fatty Acid Notation

• (18:0) = 18 C and no double bonds

• (18:1) = 18 C and one double bond

• (18:3) = 18 C and three double bonds

Table 20.1, p.496

Fatty 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

Waxes

• High molecular-weight esters

OCH2

CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH3

O CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH2

CH2CH2

CH3

46 C total for triacontyl palmitate

Fats and Oils

• Contain glycerol and fatty acids

• Glycerol is triol

• Combined with ester

bonds

Triglycerides

• Triglyceride (triacylglyceride):Triglyceride (triacylglyceride): 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

Example of triglyceride

Triglycerides

• Triglyceride (triacylglyceride):Triglyceride (triacylglyceride): 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

Triglycerides

• Physical properties depend on the fatty acid components– More carbons: higher melting point – More saturated (fewer C=C): higher melting point– Oils:Oils:

• More unsaturated fatty acids • Liquid at room temperature

– Fats:Fats: • Primarily saturated fatty acids • Semisolids or solids at room temperature

Triglycerides

• Melting points related to 3-D shape of triglyceride– Saturated fatty acids can pack closely together

• More London dispersion forces between chains• Higher melting points (above room temperature)

– Unsaturated fatty acids have cis double bonds • Bend in chain prevents close packing• Fewer London dispersion forces between them• Lower melting points (below room temperature)

Packing of Saturated vs Unsaturated Fatty Acids

Hydrogenation

• Can convert liquid oil to solid fat by adding H2 to double bonds by using H2/catalyst

– Can control hardening to produce fats of a desired consistency

– Examples: Crisco, Spry, Dexo, etc.– Margarine produced by partial hydrogenation of

polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils

Hydrogenation of triglyceride

HC

H2C

H2C C (CH2)12 CH3O

O

O

O

C (CH2)6 CH2

CH CH

CH2 (CH2)6 CH3

O

C (CH2)6 CH2

CH CH

CH2 (CH2)6 CH3

O

+ H2

catalyst

HC

H2C

H2C C (CH2)12 CH3O

O

O

O

C (CH2)6 CH2

CH2 CH2

CH2 (CH2)6 CH3

O

C (CH2)6 CH2

CH2 CH2

CH2 (CH2)6 CH3

O

Iodine or Bromine Test for Unsaturation

• Add Br2 (or I2) to C=C.

• The more Br2 or I2 you add, the greater the number of double bonds in the fat or oil

• Iodine number is a measure of unsaturation.

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

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

Soaps

– Soaps form water-insoluble salts (scum) when used in water containing Ca2+, Mg2+, and Fe3+ 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)

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

Fig 20.1, p.501

Complex Lipids

Complex 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

Membranes• Complex lipids form the membranes around cells

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

lipid bilayer, with a back-to-back arrangement of lipid monolayers– polar head groups are hydrophilic and point to aqueous

environment– nonpolar tails are hydrophobic and are inside the

bilayer– hydrophobic interactions drive bilayer formation– Rigidity of membrane depends on whether fatty acid

tails are saturated or unsaturated

Membrane bilayer

• Hydrophilic head outside

• Hydrophobic tails inside

Membrane Rigidity

• Depends on nature of fatty acid tails– Saturated fatty acids = more rigid– Unsaturated fatty acids = less rigid

– Reindeer legs• Near foot membranes have different fatty acid

composition than in other parts of animal

Fig 20.1, p.501

Membrane bilayer

• Hydrophilic head outside

• Hydrophobic tails inside

Fluid Mosaic Model

Transport across membrane

• Passive transport– Gap junctions—6 proteins make a central pore– Small molecules pass through pores

• Ions, sugars, amino acids, nucleotides• Large molecules can’t pass through

– Pore can be open or twisted shut

• Facilitated transport– Interaction between transporter and transported molecule

• Active transport—– Ions transported against concentration gradient– Energy expended to change shape of protein and transport

ion across membrane

Transport across membranes

• Active transport—– Ions transported against concentration

gradient– Energy expended to change shape of protein

and transport ion across membrane– Polar compounds transported via specific

transmembrane channels.

Fig 20.1, p.501

Complex lipids found in membranesSimple lipids

Glycerophospholipids• GlycerophospholipidsGlycerophospholipids (phosphoglycerides) are

the second most abundant group of naturally occurring lipids– found in plant and animal membranes, which

consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins

– Major phosphoacylglycerols are derived from phosphatidic acid

• glycerol + 2 fatty acids + phosphate

– Most abundant fatty acids in phosphatidic acids are palmitic (16:0), stearic (18:0), and oleic (18:1)

Glycerophospholipids

• A phosphatidic acid

– Fatty acid attached to C-2 is always unsaturated– Can also add small alcohol to the phosphate to

make a glycerophospholipid

CH2

CH

CH2-O-P-O-

O

O

O

Oglycerol

palmitic acid

oleic acid

O

O-

Glycerophospholipids

HOHO

OHOH

OH

OH

NH3+

HOCH2CHCOO-

HOCH2CH2N(CH3)3

HOCH2CH2NH2

inositol phosphatidylinositol

Name and FormulaName of Glycerophospholipid

ethanolamine

+choline lecithin

cephalin

serine cephalin

Glycerophospholipids

– a lecithina lecithin

CH2

CH

CH2

O

O

O

O

O P OCH2CH2N(CH3)3

O

O-

+

palmitic acid

linolenic acid

glycerol

choline

Glycerophospholipids

• Phosphatic acid– Glycerol, 2 fatty acids, phosphate

• Lecithins– Glycerol, 2 fatty acids, phosphate, choline

• Cephalins– Glycerol, 2 fatty acids, phosphate,

ethanolamine or serine

Sphingolipids

• Found in the myelin sheath of nerve axons– Sphingomyelin deterioration found in MS

• Contain sphingosine, a long-chain aminoalcohol

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

Glycolipids• GlycolipidGlycolipid:: complex lipid that contains a sugar

– Sugar is glucose or galactose– Cerebrosides found in brain and nerve synapses

O

(CH2)12CH3

HO

NHCR

O

H

HO

H

HO

H

HOH

H

OHO

a-glycosidic bond

a unit of -D-glucopyranose

a ceramide

Steroids

• SteroidsSteroids:: a group of plant and animal lipids that have a steroid ring structure

A B

C D

Cholesterol• Cholesterol is the most abundant steroid in

the human body, and also the most important– Component in animal plasma membranes – Precursor of all steroid hormones and bile acids

HO

Lipoproteins• Schematic of a low-density lipoprotein

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

Lipoproteins

• Protein has a higher density than lipids do

• HDL (high density lipoprotein)– Have higher protein to lipid ratio

• LDL (low density lipoprotein)– have lower protein to lipid ratio

Cholesterol Transport—from liver to peripheral cells

– Transport from the liver starts with VLDL (55 nm)• Carried in plasma

– Density increases as fat is removed• VLDL becomes LDL (22 nm)• LDL stays in the plasma for about 2.5 days

– LDL carries cholesterol to cells, where specific LDL receptors (coated pits) bind it

– LDL is taken into cells where enzymes liberate free cholesterol and cholesteryl esters

Cholesterol Transport—from peripheral cells to liver

– HDL transport cholesterol from peripheral tissues to the liver and also transfer cholesterol to LDL

– Free cholesterol in HDL is converted to cholesteryl esters (while in serum)

– HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell

– Cholesterol esters are used for the synthesis of steroid hormones and bile acids

– after HDL has delivered its cholesteryl esters to liver cells, it reenters circulation

• Cholesterol forms plaque deposits on inside of blood vessels (atherosclerosis)

• Narrows blood vessel diameter

• Lowers blood flow

• Can lead to heart attack, stroke, kidney disfunction or other problems

Levels of LDL and HDL

– Most cholesterol is carried by LDL– Normal plasma levels are 175 mg/100 mL– LDL is removed from circulation if there are

enough LDL receptors on cells– Number of LDL receptors controlled by feedback

mechanism• High cholesterol inside cell suppresses receptor

synthesis

– Hypercholesterolemia: not enough LDL receptors• High plasma cholesterol levels (up to 680 mg/100 mL)

Levels of LDL and HDL

– High LDL together with low HDL is a symptom of faulty cholesterol transport and a warning of possible atherosclerosis

– Serum cholesterol level controls cholesterol synthesis in the liver

• High serum cholesterol results in low synthesis of cholesterol in liver, and vice versa

• Statin drugs inhibit the synthesis of cholesterol

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

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

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

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)

Steroid Hormones• Glucorticoid hormonesGlucorticoid hormones

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

Aldosterone

C=O

CH2OH

O

H

H3C H

H

CHO

OH

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 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)

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

Prostaglandins

• Prostaglandins are synthesized in response to specific physiological triggers

• Made from membrane-bound 20-carbon polyunsaturated fatty acids such as arachidonic acid

COOH

Arachidonic acid1514

89

11 12

6 5

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)

COX Enzymes• 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 tissue cells

– interaction activates COX-2 and prostaglandins are synthesized

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

Leukotrienes• Synthesized from arachidonic acid

– occur mainly in leukocytes– produce muscle contractions, especially in the

lungs and thereby can cause asthma-like attacks– 100 times more potent than histamine – Many new anti-asthma drugs inhibit the synthesis

of leukotrienesOH OH

COOH

Leukotriene B4

1512

20