LIPIDS

What are Lipids? Class of biomolecules that are all water

insoluble No defining characteristic except that all

of them share the same trait: non-polar Most common are fatty acids and esters

of fatty acids Functions

Energy Storage Cell membrane Thermal blanket and cushion Precursors of hormones

Fatty Acids Fatty acids consist of a hydrocarbon

chain with a carboxylic acid at one end. A 16-C fatty acid: CH3(CH2)14-COO-

Non-polar polar General Structure:

(CH2)nCH3 COOH

n is almost always even

n = 0 : CH3COOH n = 1 : propionic acid

Fatty Acids Double bonds in fatty acids usually have

the cis configuration. Most naturally occurring fatty acids have

an even number of carbon atoms. IUPAC naming:

COOH carbon as C1 Farthest carbon is ω Total carbons/# double bonds/Δdouble bond position

Fatty Acids Some fatty acids and their common names:

14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid;

18:1 cisD9  oleic acid 18:2 cisD9,12  linoleic acid 18:3 cisD9,12,15  a-linonenic acid 20:4 cisD5,8,11,14  arachidonic acid 20:5 cisD5,8,11,14,17  eicosapentaenoic acid (an omega-3)

Essential fatty acids ALA- ω-3 FA precursor for EPA and DHA LA – ω-6 FA precursor of AA

Fatty Acid Chemistry Peroxidation

a non-enzymatic reaction catalyzed by oxygen

may occur in tissues or in foods (spoilage) the hydroperoxide formed is very reactive

and leads to the formation of free radicals which oxidize protein and/or DNA (causes aging and cancer)

principle is also used in drying oils (linseed, tung, walnut) to form hard films

Drying Oils: Application of Peroxidation

based on the ease of autoxidation and polymerization of oils (important in paints and varnishes)

the more unsaturation in the oil, the more likely the “drying” process Non-drying oils:

Castor, olive, peanut, rapeseed oils Semi-drying oils

Corn, sesame, cottonseed oils Drying oils

Soybean, sunflower, hemp, linseed, tung, oiticica oils

Fatty Acid Chemistry Transesterification

Acid-catalyzed exchange betweein R groups of esters

Frequently-used in polyester, methanolysis and biodiesel industries

Fatty Acid Chemistry Hydrogenation

Reduces double bonds on unsaturated fatty acids

Prevents oils from going rancid

Fatty Acid Chemistry Saponification

Base hydrolysis of triglycerides to produce fatty acid salts

High saponification number, shorter chain length

Soaps Types of soaps:

Sodium soap – ordinary hard soap Potassium soap – soft soap (shaving soaps are

potassium soaps of coconut and palm oils) Castile soap – sodium soap of olive oil Green soap – mixture of sodium and potassium

linseed oil Transparent soap – contains sucrose Floating soap – contains air Calcium and magnesium soaps are very poorly

water soluble (hard water contains calcium and magnesium salts –these insolubilize soaps)

Fatty Acid Chemistry Iodine Number

measures the degree of unsaturation in a given amount of fat or oil

the iodine number is the number of grams of iodine absorbed by 100 grams of fat Cottonseed oil: 103 –111 Olive oil: 79 – 88 Linseed oil: 175 –202

frequently used to determine adulteration of commercial lots of oils

HH I I

HHI2

Fatty Acid Chemistry Acetyl Number

the number of milligrams of KOH needed to neutralize the acetic acid of 1 g of acetylated fat

fatty acid

OH

acetic anhydridefatty acid

O C

O

CH3

fatty acid

OH

+

COOHH3C

titrate with standardizedKOH

acetylated fatty acid

Fatty Acid Chemistry Reichert-Meisl Number

measures the amount of volatile fatty acids (low MW and water soluble Fas)

the R-M number is the number of milliliters of 0.1N alkali required to neutralize the soluble fatty acids distilled from 5 Gm of fat

butter fat has a high R-M number Indicator of non-fat compounds in edible

fats, or volatile fatty acids

Fats and Oils fats are solids or semi solids oils are liquids melting points and boiling

points are not usually sharp (most fats/oils are mixtures)

when shaken with water, oils tend to emulsify

pure fats and oils are colorless and odorless (color and odor is always a result of contaminants) – i.e. butter (bacteria give flavor, carotene gives color)

Waxes simple esters of fatty acids

(usually saturated with long chain monohydric alcohols) Beeswax – also includes some

free alcohol and fatty acids Spermaceti – contains cetyl

palmitate (from whale oil) –useful for pharmaceuticals (creams/ointments; tableting and granulation)

Carnauba wax – from a palm tree from brazil – a hard wax used on cars and boats

H3C (CH2)14 C

O

O CH2 (CH2)28-CH3

long chain alcoholfatty acid

Bee’s wax

Spermaceti source

Carnauba wax source

Glycerides Function

Storage of energy Cushions

O

OH

OH

R

O

O

OH

O

R

O

R

O

O

O

R

O

R

O

OR

O

MONOGLYCERIDE DIGLYCERIDE TRIGLYCERIDE

Triglycerides Esters of fatty acids and glycerol Constituent of fats and oils

Phosphoglycerides aka glycerophospholipids Major constituent of cell

membranes Structure

Glycerol backbone with esterifies fatty acids at C1 and C2

Fatty acids are usually non-identical

Phosphate group attached to C1

A polar group is usually esterified to Pi (usually serine, choline, ethanolamine, glycerol, or inositol

X = H (phosphatidic acid) - precursor to other phospholipids

X = CH2-CH2-N+(CH3)3 phosphatidyl choline

X = CH2-CH(COO-)NH3+ phosphatidyl serine

X = CH2-CH2-NH3+ phosphatidyl ethanolamine

Phosphoglycerides Structure=Function

Polar region – glycerol, phosphate group, X

Nonpolar region – fatty acid

Amphiphatic character

Ideal for forming bilayers

Phosphoglyceride

Phosphatidyl inositol Inositol as a polar head group Has roles in cell signaling as well as a cell

membrane component

O P

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

OH

H

OH

H

H

OHH

OH

H

O

H OH

phosphatidyl- inositol

Ether glycerophospholipids Possess an ether linkage

instead of an acyl group at the C-1 position of glycerol PAF ( platelet activating factor) -

a potent mediator in inflammation, allergic response and in shock (also responsible for asthma-like symptom

The ether linkage is stable in either acid or base

Plasmalogens: cis a,b-unsaturated ethers The alpha/beta unsaturated

ether can be hydrolyzed more easily

Sphingolipids derivatives of the lipid

sphingosine, which has a long hydrocarbon tail, and a polar domain that includes an amino group

Like phosphoglycerides, are also constituents of cell membranes

Can be reversibly phosphorylated and utilized as signaling molecule

Sphingolipid Derivatives Ceramide - amino group

of sphingosine forms an amide bond with a fatty acid carboxyl

Sphingomyelin has a phosphocholine or phosphethanolamine head group. common constituent of

plasma membranes similar in size and shape

to the glycerophospholipid phosphatidyl choline

H2CHC

OH

CH

NH CH

C

CH2

CH3

H

OH

( )12

C

R

O

ceramide

Sphingolipid Derivatives Cerebroside a sphingolipid

(ceramide) with a monosaccharide such as glucose or galactose as polar head group.

Ganglioside – a ceramide with polar head group that is a complex oligosaccharide, including the acidic sugar derivative sialic acid

Both are collectively known as glycosphingolipids and are commonly found on the outer leaflet of the cell membrane

cerebroside with -galactose head group

H2CHC CH

NH CH

C

CH2

CH3

OH

C

R

O

OH O

H H

H

OHH

OH

CH2OH

HO

H

( )12

Ganglioside Structure

Ganglioside Cerebrosides

One sugar molecule Galactocerebroside – in neuronal membranes Glucocerebrosides – elsewhere in the body

Sulfatides or sulfogalactocerebrosides A sulfuric acid ester of galactocerebroside

Globosides: ceramide oligosaccharides Lactosylceramide

2 sugars ( eg. lactose) Gangliosides

Have a more complex oligosaccharide attached Biological functions: cell-cell recognition; receptors for

hormones

Cardiolipids A polyglycerol phospholipid; makes up 15% of

total lipid-phosphorus content of the myocardium – associated with the cell membrane

Cardiolipids are antigenic and as such are used in serologic test for syphilis (Wasserman test)

C

H2C O

O

H2C O P

O

OH

O

C

O

R1

C

O

R2

CH2 C

OH

H

CH2 O P O

OH

O

CH2

C OH

CH2O

C

O

R3

C

O

R4

H

glycerolglycerol

glycerol

Sulfolipids also called sulfatides or cerebroside sulfates contained in brain lipids sulfate esters of cerebrosides present in low levels in liver, lung, kidney, spleen, skeletal

muscle and heart function is not established

Lipid Storage Diseases

Lipid Storage Diease a group of inherited metabolic disorders in

which harmful amounts of fatty materials (lipids) accumulate in various tissues and cells in the body

also known as sphingolipidoses genetically acquired due to the deficiency or absence of a

catabolic enzyme Tay Sachs disease Gaucher’s disease Niemann-Pick disease Fabry’s disease

Tay Sachs Disease

Fabry’s Disease

Niemann Pick Disease

Cholesterol and related compounds

Cholesterol an important constituent of cell

membranes, has a rigid ring system and a short branched hydrocarbon tail. serves as a component of

membranes of cells (increases or moderates membrane fluidity)

precursor to steroid hormones and bile acids

storage and transport –cholesterol esters

Cholesterol is largely hydrophobic.

But it has one polar group, a hydroxyl, making it amphipathic.

C holestero lH O

cholesterol PDB 1N83

Steroid Ring System

A B

C D1

2

34

56

7

8910

1112

13

14 15

16

1718

19

Eicosanoids Includes prostaglandins and related

compounds Derivatives of arachidonic acid Serves as local hormones and

intercellular signaling Key hormones in inflammation responseCOOH

20

8

12

prostanoic acid

9

1115

Eicosanoids Types of

Eicosanoids Prostaglandins Prostacyclins Thromboxanes Leukotrienes epoxyeicosatrien

oic acids.

Biological Functions Inflammation Fever regulation of blood

pressure blood clotting immune system

modulation control of reproductive

processes and tissue growth

regulation of the sleep/wake cycle

Terpenes simple lipids, but lack

fatty acid component formed by the

combination of 2 or more molecules of 2-methyl-1,3-butadiene (isoprene)

monoterpene (C-10) – made up of 2 isoprene units

sesquiterpene (C-15) – made up of 3 isoprene units

diterpene (C-20) – made up of 4 isoprene units

limonene

CHO

citronellal

OH

menthol camphene

HOH

squalene lanosterol

Terpenes tetraterpenes (C-40) are not

as common as mono, di, and triterpenes include the carotenoids such as

beta-carotene (precursor of vitamin A) and lycopene found in tomatoes

usually colorful compounds due to highly conjugated system

polyisoprenoids or polyprenols consist of numerous isoprene adducts (8 – 22) examples include dolichol

phosphate, undecaprenyl alcohol (bactoprenol) and the side chains of vitamins K, vitamin E and coenzyme Q

Lipid-linked proteins and Lipoproteins

Lipid-linked proteins Proteins that have lipids covalently bonded to them Usually found in cell membranes 3 types are most common:

Prenylated proteins Farnesylated proteins (C15 isoprene unit) Geranylgeranylated proteins (C20 isoprene unit)

Fatty acylated proteins Myristoylated proteins (C14) Palmitoylated proteins (C16)

glycosylphosphatidylinositol-linked proteins (GPI-linked proteins) occur in all eukaryotes, but are particularly abundant in parasitic

protozoa located only on the exterior surface of the plasma membrane

Fatty acylated proteins

Prenylated proteins

GPI-linked proteins

Lipoproteins particles found in plasma that transport

lipids including cholesterol lipoprotein classes

chylomicrons: take lipids from small intestine through lymph cells

very low density lipoproteins (VLDL) intermediate density lipoproteins (IDL) low density lipoproteins (LDL) high density lipoproteins (HDL)

LipoproteinLipoprotein class

Density (g/mL)

Diameter (nm)

Protein % of dry wt

Phospholipid %

Triacylglycerol % of dry wt

HDL 1.063-1.21 5 – 15 33 29 8

LDL 1.019 – 1.063

18 – 28 25 21 4

IDL 1.006-1.019

25 - 50 18 22 31

VLDL 0.95 – 1.006

30 - 80 10 18 50

chylomicrons

< 0.95 100 - 500 1 - 2 7 84