Lipids

Types of Lipids Fatty Acids Fats, and Oils Chemical Properties of Triglycerides

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:
Storage lipids Structural lipids

 The fats and oils used almost universally as stored forms of energy in living organisms are derivatives of fatty acids.

The fatty acids are hydrocarbon derivatives, at about the same low oxidation state (that is, as highly reduced) as the hydrocarbons in fossil fuels. The cellular oxidation of fatty acids (to CO2 and H2O), like the controlled, rapid burning of fossil fuels in internal combustion engines, is highly exergonic.
Two types of fatty acidcontaining compounds,

Triacylglycerols Waxes
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Fatty acids
Carboxylic acid derivatives of long chain hydrocarbons
Nomenclature (somewhat confusing)
Stearate stearic acid C18:0 n-octadecanoic acid

General structure:

CH3

(CH2)n COOH

n = 0 : CH 3COOH n = 1 : propionic acid

n is almost always even

Fatty acids
Common fatty acids n = 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 FAs:
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 acid n = 24; lignoceric acid n = 26; cerotic acid

Types of Lipids
Lipids with fatty acids Waxes Fats and oils (trigycerides) Phospholipids Sphingolipids Lipids without fatty acids Steroids
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Lipids are classified as simple or complex

1. Simple lipid a. Fatty acids b. neutral fats (monoglyceride,

diglycerde, and triglyceride) c. waxes 2. Complex lipids a. Phospholipids b. Glycolipids c. Lipoproteins

3. Derived lipids

Triglyceride

Phosphatidic acid

Omega Fatty acid

Cis- Trans Fatty acid

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
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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 = CC bonds Unsaturated = one or more C=C bonds
COOH palmitic acid, a saturated acid COOH palmitoleic acid, an unsaturated fatty acid
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Structures
Saturated fatty acids Fit closely in regular pattern
COOH COOH COOH

Unsaturated fatty acids Cis double bonds

H C C

cis double bond

COOH
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Properties of Saturated Fatty Acids

Contain only single CC bonds
Closely packed Strong attractions between chains High melting points Solids at room temperature

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Properties of Unsaturated Fatty 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

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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 69C oleic acid mp 13C linoleic acid mp -17C
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Neutral lipids
Glycerides (fats and oils) ; glycerides
Glycerol
CH2OH H OH CH2OH OH OH OH

glycerol is a prochiral molecule

Ester of glycerol - mono glycerides, diglycerides and

triglycerides

Waxes simple esters of long chain alcohols

GLYCERIDES
O O OH OH R O O O OH O O MONOGLYCERIDE DIGLYCERIDE R R R O O O TRIGLYCERIDE R O R O

Function: storage of energy in compact form and cushioning

Fats and Oils

Formed from glycerol and fatty acids
O CH2 OH CH CH2 OH OH + HO C O (CH2)14CH3

HO C (CH2)14CH3 O HO C (CH2)14CH3

glycerol

palmitic acid (a fatty acid)

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Triglycerides (triacylglcerols)
Esters of glycerol and fatty acids
ester bonds O CH2 CH CH2 O O O C O C (CH2)14CH3 O C + H 2O H2O
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(CH2)14CH3 + H2O

(CH2)14CH3 +

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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

Packing of fatty acids into stable aggregates

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Fatty acid reactions

salt formation
RCO2H NaOH RCO2-Na + (a soap)

ester formation
R'OH + RCO 2H -H20 RCO2R'

lipid peroxidation
R' R H H non-enzymatic OOH very reactive O2 R R'

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 CC bonds

Hydrolysis
Split by water and acid or enzyme catalyst Produce glycerol and 3 fatty acids
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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
O CH2 O CH CH2 O O C O C (CH2)5CH CH(CH2)7CH3 O C (CH2)5CH CH(CH2)7CH3 + 3 H2 (CH2)5CH CH(CH2)7CH3 Ni

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Product of Hydrogenation
O CH 2 CH CH 2 O O O C O C (CH 2)14CH 3 O C (CH2)14CH 3 (CH 2)14CH 3

Hydrogenation converts double bonds in oils to single bonds. The solid products are used to make margarine and other hydrogenated items.
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Hydrolysis
Triglycerides split into glycerol and three fatty acids (H+ or enzyme catalyst)
O CH2 CH CH2 O O O C O C (CH2)14CH3 O C (CH2)14CH3 CH2 OH CH CH2 OH OH + O 3 HO C (CH2)14CH3
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(CH2)14CH3 H+ +3 H2O

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

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Saponification
O CH2 O CH CH2 O O C (CH2)16CH3 O C (CH2)16CH3 + 3 NaOH O C (CH2)16CH3 CH2 OH CH CH2 O

+OH + 3 Na O C (CH2)14CH3 salts of fatty acids (soaps) OH

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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
H H I2 I H I H

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

Acetyl number
some fatty acids have hydroxyl groups
OH H3C (CH2)21 CH COOH cerebronic acid H3C (CH2)5 OH CH CH2 CH CH (CH2)7 COOH ricinoleic acid

The acetyl number gives the proportion of these hydroxylcontaining fatty acids in a given sample of fat or oil
acetic anhydride fatty acid OH fatty acid O C O acetylated fatty acid H3C CH3 fatty acid OH + COOH

titrate with standardized KOH

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

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Fatty acid composition of three food fats

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WAXES
simple esters of fatty acids (usually saturated with long chain monohydric alcohols)
O H3C (CH 2)14 C O CH 2 (CH 2)28-CH 3

fatty acid long chain alcohol

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

Spermaceti source

Carnauba wax source

Bees wax

Waxes
H3C (CH2)14 CH2-OH cetyl alcohol

H3C H3C

(CH2)24 CH2-OH (CH2)28 CH2-OH

hexacosanol triacontanol (myricyl alcohol)

Examples of long chain monohydric alcohols found in waxes

Structural lipids

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Phospholipids
the major components of cell membranes
phosphoglycerides
O

fatty acids (hydrophobic tail) glycerol

O OO P O O X R'

phosphate

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

fatty acids (hydrophobic tail) glycerol

O OO P O O X R'

phosphate

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Sphingolipids
Based on sphingosine instead of glycerol
sphingosine OH OH NH 2

HO

long chain hydrocarbon

NH 2 OH

attach fatty acid here attach polar head group here

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Sphingomyelin

HO O NH OO P O

R' O

usually palmitic acid

N(CH3)+ 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 asthmalike symptoms) Plasmalogens: cis a,b-unsaturated ethers

Ether glycerophospholipids
O -O P O H2C O CH O C CH 3 O
H

CH 3 O CH 2 CH 2 N CH 3
H2C O CH O C O

CH 3 O CH 2 CH 2 N CH 3 CH 3

CH 3

-O

P O CH 2

CH 2
H

platelet activating factor or PAF

A choline plasmalogen

glycolipids

HO O NH O

R' SUGAR polar head is a sugar

beta link age

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

GLYCOLIPIDS
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

N-Acetyl-D-galactosamine
CH 2OH OH O OH H H OH H O H NH C CH 3 O H3C C NH CHOH CHOH CH 2OH H H O O H H OH O O CH 2OH

D-galactose
CH 2OH H O H H H OH O

D-glucose
CH 2OH O OH H H H HO H C OH H C O H C NH C C H R O CH 2

D-Galactose

O COO-

OH

N-acetylneuraminidate (sialic acid)

A ganglioside (GM1)

Cardiolipids
O O R2 C O H2C C H2C O H O C O P OH glycerol glycerol O R1 H CH2 C OH CH2 O R4 O C O P OH glycerol O H O CH2 C CH2 O O C R3

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)

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 Gauchers disease Niemann-Pick disease Fabrys disease

Blood groups
determined by various glycolipids on RBCs
A antigens B antigens
Gal Gal NAc-Glu-sphingosine
Ac N

AcN

Gal

Glu-sphingosine

L-Fucose

L-Fucose

H antigens
Gal NA c--Glu-sphingosine L-Fucose

(found on type O blood cells)

not recognized by anti-A or anti-B antibodies

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Cholesterol and cholesterol esters

H3C CH3 CH3 H OH H H drawn this way R usually palmitate hydrophillic

hydrophobic O

STEROID NUMBERING SYSTEM

18 12 11 19 1 2 A 3 4 C 13 14 7 6 17 D 15 16

9 10 8 B 5

Cholesterol sources, biosynthesis and degradation

diet: only found in animal fat biosynthesis: primarily synthesized in the liver from acetylcoA; biosynthesis is inhibited by LDL uptake degradation: only occurs in the liver

Cholesterol and cholesterol esters

H HO

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

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Prostaglandins and other eicosanoids

local hormones, unstable, key mediators of inflammation derivatives of prostanoic acid

COOH 20

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)

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

OH COOH H C5H11 H S Cys gGlu LEUKOTRIENE F 4 (LTF4) C5H11

OH COOH S Cys gGlu LEUKOTRIENE C 4 (LTC 4) Gly

peptidoleukotrienes

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Lipid-linked proteins
Lipid-linked proteins (different from lipoproteins)
lipoproteins that have lipids covalently attached to them these proteins are peripheral membrane proteins

Lipid-linked 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)

Lipid-linked proteins
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
HDL

Density (g/mL)
1.063-1.21

Diameter (nm)
5 15

Protein % Phosphol of dry wt ipid %

33 29

Triacylglycerol % of dry wt
8

LDL

1.019 1.063 1.006-1.019

18 28

25

21

IDL

25 - 50

18

22

31

VLDL

0.95 1.006

30 - 80

10

18

50

chylomicrons

< 0.95

100 - 500

1-2

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Composition and properties of human lipoproteins

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

Lipoprotein structure

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