lecture 5 - lipids

Lipids

Types of LipidsFatty Acids

Fats, and OilsChemical Properties of Triglycerides

1

Introduction• Definition: water insoluble compounds

• Most lipids are fatty acids or ester of fatty acid• They are soluble in non-polar solvents such as petroleum

ether, benzene, chloroform

• Functions• Energy storage• Structure of cell membranes• Thermal blanket and cushion• Precursors of hormones (steroids and prostaglandins)

• Types:• Fatty acids• Neutral lipids• Phospholipids and other lipids

Fatty acids• Carboxylic acid derivatives of long chain

hydrocarbons– Nomenclature (somewhat confusing)

• Stearate – stearic acid – C18:0 – n-octadecanoic acid

– General structure:

(CH2)nCH3 COOH

n is almost always even

n = 0 : CH3COOH n = 1 : propionic acid

Fatty acids

• Common fatty acidsn = 4 butyric acid (butanoic acid)n = 6 caproic acid (hexanoic acid)n = 8 caprylic acid (octanoic acid)n = 10 capric acid (decanoic acid)

Fatty acids

• common FA’s: n = 12: lauric acid (n-dodecanoic acid; C12:0)n = 14: myristic acid (n-tetradecanoic acid; C14:0)

n = 16: palmitic acid (n-hexadecanoic acid; C16:0)

n = 18; stearic acid (n-octadecanoic acid; C18:0)

n = 20; arachidic (eicosanoic acid; C20:0)

n= 22; behenic acidn = 24; lignoceric acidn = 26; cerotic acid

Types of Lipids

• Lipids with fatty acidsWaxesFats and oils (trigycerides)PhospholipidsSphingolipids

• Lipids without fatty acidsSteroids

6

Fatty Acids

• Long-chain carboxylic acids• Insoluble in water• Typically 12-18 carbon atoms (even number)• Some contain double bonds

corn oil contains 86% unsaturated fatty acids and

14% saturated fatty acids

7

Fatty acids

• Fatty acids can be classified either as:– saturated or unsaturated– according to chain length:

• short chain FA: 2-4 carbon atoms• medium chain FA: 6 –10 carbon atoms• long chain FA: 12 – 26 carbon atoms• essential fatty acids vs those that can be biosynthesized

in the body:– linoleic and linolenic are two examples of essential fatty acid

Saturated and Unsaturated Fatty Acids

Saturated = C–C bondsUnsaturated = one or more C=C bonds

9

COOH

COOH

palmitoleic acid, an unsaturated fatty acid

palmitic acid, a saturated acid

Structures

Saturated fatty acids• Fit closely in regular pattern

Unsaturated fatty acids• Cis double bonds

10

COOHCOOHCOOH

C CH H

COOHcis double bond

Properties of SaturatedFatty Acids

• Contain only single C–C bonds

• Closely packed

• Strong attractions between chains

• High melting points

• Solids at room temperature

11

Properties of UnsaturatedFatty Acids

• Contain one or more double C=C bonds• Nonlinear chains do not allow molecules to pack

closely• Few interactions between chains• Low melting points• Liquids at room temperature

12

Stearic acid is saturated and would have a higher melting point than the unsaturated fatty acids.

Linoleic has two double bonds, it would have a lower mp than oleic acid, which has one double bond.

stearic acid mp 69°Coleic acid mp 13°C

linoleic acid mp -17°C

13

Neutral lipids

• Glycerides (fats and oils) ; glycerides– Glycerol

– Ester of glycerol - mono glycerides, diglycerides and triglycerides

• Waxes – simple esters of long chain alcohols

CH2OH

CH2OH

OHH OH

OH

OH

glycerol is a prochiral molecule

GLYCERIDES

O

OH

OH

R

O

O

OH

O

R

O

R

O

O

O

R

O

R

O

OR

O

MONOGLYCERIDE DIGLYCERIDE TRIGLYCERIDE

Function: storage of energy in compact form and cushioning

Fats and Oils

Formed from glycerol and fatty acids

17

+

HO C (CH2)14CH3

O

HO C (CH2)14CH3

O

HO C (CH2)14CH3

O

glycerol palmitic acid (a fatty acid)

CH

CH2 OH

OH

CH2 OH

Triglycerides (triacylglcerols)

Esters of glycerol and fatty acids

18

CH

CH2

CH2 O

O

O

C (CH2)14CH3

O

C (CH2)14CH3

O

C (CH2)14CH3

O

ester bonds

+

+

+

H2O

H2O

H2O

Stereospecific numbering

• Carbon 2 of triglycerides is frequently asymmetric since C-1 and C-3 may be substituted with different acyl groups

• By convention we normally draw the hydroxyl group at C-2 to the left and use the designation of sn2 for that particular substituent

• C-1 and C-3 of the glycerol molecule become sn1 and sn3 respectively

Fatty acid reactions

• salt formation

• ester formation

• lipid peroxidation

RCO2H RCO2-Na+NaOH

(a soap)

R'OH + RCO2H RCO2R'-H20

R

R'

H H

R R'

OOH

O2

non-enzymatic

very reactive

Lipid 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

Properties of Triglycerides

Hydrogenation• Unsaturated compounds react with H2

• Ni or Pt catalyst• C=C bonds C–C bonds

Hydrolysis• Split by water and acid or enzyme catalyst• Produce glycerol and 3 fatty acids

22

Hydrogenated fats

• hydrogenation leads to either saturated fats and or trans fatty acids

• the purpose of hydrogenation is to make the oil/fat more stable to oxygen and temperature variation (increase shelf life)

• example of hydrogenated fats: Crisco, margarine

Hydrogenation

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CH

CH2

CH2 O

O

O

C

O

(CH2)5CH CH(CH2)7CH3

C

O


C

O

+


H23Ni

Product of Hydrogenation

Hydrogenation converts double bonds in oils to single bonds. The solid products are used to make margarine and other hydrogenated items.

25

CH

CH2

CH2 O

O

O

C (CH2)14CH3

O

C (CH2)14CH3

O

C (CH2)14CH3

O

Hydrolysis

Triglycerides split into glycerol and three fatty acids (H+ or enzyme catalyst)

26

CH

CH2

CH2 O

O

O

C (CH2)14CH3

O

C (CH2)14CH3

O

C (CH2)14CH3

O H2O+3

3+ HO C (CH2)14CH3

O

CH

CH2 OH

OH

CH2 OH

H+

Saponification and Soap

• Hydrolysis with a strong base• Triglycerides split into glycerol and the salts of fatty

acids • The salts of fatty acids are “soaps”• KOH gives softer soaps

27

Saponification

28

3+ Na+ -O C (CH2)14CH3

O

CH

CH2 OH

OH

CH2 OH

CH

CH2

CH2 O

O

O

C (CH2)16CH3

O

C

O

(CH2)16CH3

(CH2)16CH3C

O

+ 3 NaOH

salts of fatty acids (soaps)

Analytical methods to evaluate lipids

• saponification number• iodine value (Hanus method)• free fatty acids• acetyl number• Reichert-Meissl number• HPLC/GC (for more precise analysis)

Saponification number

• gives some clue as to the average size of fatty acids in a given sample of fat

• defined as the number of milligrams of KOH needed to neutralize the fatty acids in 1 Gm of fat

• butter (large proportion of short chain FAs) sap. no. 220 – 230

• oleomargarine (long chain FAs) sap. No is 195 or less

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

HHI I

HHI2

Acetyl number• some fatty acids have hydroxyl groups

(CH2)21H3C CH

OH

COOH

cerebronic acid

(CH2)5H3C CH CH2

OH

CH CH (CH2)7 COOH

ricinoleic acid

The acetyl number gives the proportion of these hydroxyl-containing fatty acids in a given sample of fat or oil

fatty acid

OH

acetic anhydridefatty acid

O C

O

CH3

fatty acid

OH

+

COOHH3C

titrate with standardizedKOH

acetylated fatty acid

Acetyl number

• the acetyl number is the number of milligrams of KOH needed to neutralize the acetic acid of 1 Gm of acetylated fat– examples:

• castor oil – 146 –150• cod liver oil – 1.1• cottonseed oil – 21 – 25• olive oil – 10.5• peanut oil – 3.5

Reichert – Meissl number

• Measures the amount of volatile fatty acids (low MW and water soluble FAs)

• 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

WAXES• simple esters of fatty acids (usually saturated with long

chain monohydric alcohols)

H3C (CH2)14 C

O

O CH2 (CH2)28-CH3

long chain alcohol

fatty acid

Beeswax – also includes some free alcohol and fatty acidsSpermaceti – contains cetyl palmitate (from whale oil) –useful forPharmaceuticals (creams/ointments; tableting and granulation)Carnauba wax – from a palm tree from brazil – a hard wax used oncars and boats

Bee’s wax

Spermaceti source

Carnauba wax source

Waxes

(CH2)14H3C CH2-OH cetyl alcohol

(CH2)24H3C CH2-OH hexacosanol

(CH2)28H3C CH2-OH triacontanol (myricyl alcohol)

Examples of long chain monohydric alcohols found in waxes

Phospholipids

• the major components of cell membranes– phosphoglycerides

O R

O R'

O

P

O

O

O

O-

X

Ofatty acids (hydrophobic tail)

glycerol

phosphate

Phospholipids are generally composed of FAs, a nitrogenous base, phosphoricacid and either glycerol, inositol or sphingosine

O R

O R'

O

P

O

O

O

O-

X

Ofatty acids (hydrophobic tail)

glycerol

phosphate

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

Sphingolipids

OH

NH2

OH

NH2

OH

HO R long chain hydrocarbon

attach fatty acid here

attach polar head group here

sphingosine

Based on sphingosine instead of glycerol

Sphingomyelin

NH

O

HO R

PO

O-

O

N(CH3)+

R'

O

usually palmitic acid

phosphatidyl choline (also can be ethanolamine)

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 symptoms)

– Plasmalogens: cis ,-unsaturated ethers

Ether glycerophospholipids

H2C CH

O

CH2

O

O

P

O

-O O

C O

CH3

CH2 CH2 N

CH3

CH3

CH3

platelet activating factor or PAF

H2C CH

O

CH2

O

O

P

O

-O O

C O

CH2 CH2 N

CH3

CH3

CH3

A choline plasmalogen

H

H

glycolipids

NH

O

HO R

R'

O

SUGAR polar head is a sugar

beta linkage

There are different types of glycolipids: cerebrosides, gangliosides,lactosylceramides

GLYCOLIPIDSGLYCOLIPIDS• 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

Gangliosides

• complex glycosphingolipids that consist of a ceramide backbone with 3 or more sugars esterified,one of these being a sialic acid such as N-acetylneuraminic acid

• common gangliosides: GM1, GM2, GM3, GD1a, GD1b, GT1a, GT1b, Gq1b

O

CH2OH

H OH

H

OH

OH

O

O

CH2OH

H NH

H

OH

O

CH2OH

H OH

H

H

O

CH2OH

H OH

H

H

OH H

O

H

O

O

CH2HC

HC

NH

C O

R

HO

C

C

O

O

C O

CH3

NH

H

CHOH

CHOH

OH

CH2OH

H

H

COO-C

O

H3C

H

H

H

H

D-Galactose

N-Acetyl-D-galactosamine D-galactose D-glucose

N-acetylneuraminidate (sialic acid)

A ganglioside (GM1)

Cardiolipids

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

A polyglycerol phospholipid; makes up 15% of total lipid-phosphoruscontent of the myocardium – associated with the cell membrane

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

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

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

enzyme• examples:

• Tay Sachs disease• Gaucher’s disease• Niemann-Pick disease• Fabry’s disease

Blood groups

• determined by various glycolipids on RBCs

• A antigens

• B antigens

• H antigens

AcN Gal

L-Fucose

AcN Glu-sphingosine

Gal Gal NAc-Glu-sphingosine

L-Fucose

Gal NAc--Glu-sphingosine

L-Fucose

not recognized by anti-A or anti-B antibodies

(found on type O blood cells)

Cholesterol and cholesterol esters

CH3

CH3

H

OH

H3C

HH

hydrophillic

hydrophobic

R

O

usually palmitate

drawn this way

STEROID NUMBERING SYSTEM

A B

C D1

2

3

45

6

7

89

10

1112

13

14 15

16

1718

19

Cholesterol sources, biosynthesis and degradation

• diet: only found in animal fat• biosynthesis: primarily synthesized in the liver from acetyl-

coA; biosynthesis is inhibited by LDL uptake• degradation: only occurs in the liver

Cholesterol and cholesterol esters

HO

HH

Functions: -serves as a component of membranes of cells (increases or moderates membrane fluidity -precursor to steroid hormones -storage and transport – cholesterol esters

Prostaglandins and other eicosanoids

• local hormones, unstable, key mediators of inflammation

• derivatives of prostanoic acid

COOH

20

8

12

prostanoic acid

Functions of eicosanoids

• Prostaglandins – particularly PGE1 – block gastric production and thus are gastric protection agents

• Misoprostol (Cytotec) is a stable PGE1 analog that is used to prevent ulceration by long term NSAID treatment

• PGE1 also has vasodilator effects– Alprostadil (PGE1) – used to treat infants with congenital

heart defects– Also used in impotance (Muse)

C5H11

H S

Cys

gGlu

OH

COOH

LEUKOTRIENE F4 (LTF4)

C5H11

H S

Cys

OH

COOH

Gly

gGlu

LEUKOTRIENE C4 (LTC4)

Leukotrienes are derived from arachidonic acid via the enzyme 5-lipoxygenase which converts arachidonic acid to 5-HPETE (5-hydroperoxyeicosatetranoic acid) and subsequently bydehydration to LTA4

peptidoleukotrienes

Leukotrienes

65

SUMMARY OF ABOVE DONE THINGS

Lipid-linked proteins

• Lipid-linked proteins (different from lipoproteins)– lipoproteins that have lipids covalently attached to

them– these proteins are peripheral membrane proteins


• 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)

Lipoprotein 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

Composition and properties of human lipoproteins

most proteins have densities of about 1.3 – 1.4 g/mL and lipid aggregates usuallyhave densities of about 0.8 g/mL

Lipoprotein structure

lecture 5 - lipids

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