LIPIDS

Introduction • Definition: water insoluble compounds

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

ether, benzene, chloroform

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

• Types: • Simple lipids (triglycerides, waxes) • Composite lipids (phospholipids, glycolipids) • Precursors and lipids derivatives (fatty acids, steroids)

Properties of 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)

Fatty acids

• Fatty acids can be classified either as: saturated (C-C bonds) or unsaturated (also C=C)

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

– oleic, stearic – nonessential

liquid (C1 to C6), solid (from C7)

Fatty acids

• Carboxylic acid are derivatives of long chain hydrocarbons

– Nomenclature

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

– General structure of saturated fatty acids:

Cn H2n+1 COOH

n - carbon atoms in a molecule

Fatty acids

• Common medium-chain saturated fatty acids:

C3H7COOH butyric acid (butanoic acid) – short chain FA

C5H11COOH caproic acid (hexanoic acid)

C7H15COOH caprylic acid (octanoic acid)

C9H19COOH capric acid (decanoic acid)

CH36

CH25

CH24

CH23

CH22

COOH1 caproic acid

Fatty acids

• common long-chain saturated FA’s:

C11H23COOH : lauric acid (n-dodecanoic acid; C12:0)

C13H27COOH : myristic acid (n-tetradecanoic acid; C14:0)

C15H31COOH : palmitic acid (n-hexadecanoic acid; C16:0)

C17H35COOH; stearic acid (n-octadecanoic acid; C18:0)

C19H39COOH; arachidic (eicosanoic acid; C20:0)

C23H47COOH; lignoceric acid

C25H51COOH; cerotic acid

Less common fatty acids

• iso – isobutyric acid

• odd carbon fatty acid – propionic acid

• hydroxy fatty acids – ricinoleic acid, dihydroxystearic acid, cerebronic acid (found in higher plants)

• cyclic fatty acids – hydnocarpic, chaulmoogric acid (nonedible fat and oil isolated from chaulmoogra oil, used in LEPROSY treatment)

R

H3C

H3C H3C

R

CH3

(CH2)12-CO2H (CH2)10-CO2H

chaulmoogric acid hydnocarpic acid

R= COOH

Unsaturated fatty acids • Monoenoic acid (monounsaturated) Cn H2n-1 COOH

There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond.

Double bond is always

cis in natural fatty acids.

COOH

Elaidic acid

18:1 (9trans)

C10

C9

CH211

CH28

(CH2)6CH318

(CH2)6 COOH1

H H

Oleic acid 18:1 n-9(cis) or 18:1 (9Z)

Unsaturated fatty acids

• Dienoic acid: linoleic acid 18:2 (9cis, 12cis)

(9Z, 12Z)

(CH2)4CH3 CH=CH CH2 CH=CH (CH2)7 COOH

cis

linoleic acid

Trienoic acid: linolenic acid 18:3 (9cis, 12cis, 15cis)

(9Z, 12Z, 15Z)

Unsaturated fatty acids • Various conventions are in use for indicating the

number and position of the double bond(s)

HC CH(CH2)7COOH(CH2)7H3C

1918

10

18:1,9 or 9 18:1

H3C CH2CH2CH2CH2CH2CH2CH2CH CH(CH2)7COOH

191017n

2 3 4 5 6 7 8 9 10 18

9, C18:1 or n-9, 18:1

In chemistry:

In biochemistry:

COOH

COOH

COOH

18:0 18: 1 18:3

Melt.p. 70oC 16oC -11oC

Comparison of melting points

Saturated FA (highest melting point)

Unsaturated trans (intermediate m.p.)

Unsaturated cis (lowest m.p.)

Unsaturated fatty acids

• Polyenoic acid (polyunsaturated, tetranoic acid)

COOH

CH3

Arachidonic acid 20:4 (5Z,8Z,11Z,14Z)

(Omega 6) Fatty acids that contain at least two double bonds, one of them at C6

(carbon atom numbering starts from CH3 group).

LINOLEIC ACID 18:2 (9,12) is main representative acid of this group

(Omega 3) Fatty acids that contain at least two double bonds, one of them at C3

(starting from CH3 group)

LINOLENIC ACID 18:3 (9,12,15) is the basic acid of this group

The Essential Fatty Acids (EFA) are a group of fatty acids that are essential to human

health

CH7

CH2

CH CH

(CH2)7 COOH18

CH6

CH25

CH4

CH3

CH22

CH31

CH7

CH28

CH9

CH10

(CH2)7 COOH18

CH6

(CH2)4CH31

Function of EFAs • Formation of healthy cell membranes

• Proper development and functioning of the brain and nervous system

• Production of hormone-like substances called Eicosanoids –Thromboxanes

–Leukotrienes

–Prostaglandins

They are responsible for regulating blood pressure, blood viscosity, immune and inflammatory responses.

Omega-3 sources: Flaxeed oil/canola oil

Fish liver oils/Fish eggs

Human Milk

Seafood/Fatty fish

- albacore tuna

- mackerel

- salmon

-sardines

Omega-6 sources: Corn oil

Peanut oil

Cottonseed oil

Soybean oil

Many plant oils

They are not present in any olive oil!

Proper n-6 to n-3 ratio in a diet is 4:1

Soaps

hard

-sodium soaps

e.g. soap bar

C17H35COO-Na+

soft

-potassium soaps, e.g shampoo,

shaving soaps, liquid soaps

C17H35COO-K+

water insoluble

-barium, magnesium, calcium soaps

(C15H31COO)2Ba

Soaps don’t work effectively in hard water!

Amphipatic (amphiphilic) nature of a soap

water soluble

polar hydrophilic

carboxylate group COO-

nonpolar hydrophobic

hydrocarbon chain

e.g. stearate C17H35-

Soaps

++

+

+

+ +

+

+

+

+ +

+

Na+

fat

waterO

HH

Soaps solution

- a micelle

(emulsion type o/w)

Organization of soaps

molecules in water

Detergents

Synthesis of detergents

(CH2)n-CH3

n=10-20

H2SO

4

OSO2H

(CH2)n-CH3NaOH

OSO2 Na+

(CH2)n-CH3

_

alkylbenzene alkylbenzenesulfonic acid sodium salt

of alkylbenzenesulfonic acid

Detergents work effectively in hard water – their barium or magnesium

salts are water soluble

Simple lipids

• Glycerides (fats and oils) – Glycerol

– Esters of glycerol - monoglycerides, diglycerides and triglycerides

• Waxes – simple esters of long chain alcohols and long chain fatty acids

C OHH

CH2OH

CH2OH

glycerol

GLYCERIDES

Function: storage of energy in compact form and cushioning

CH2

C

CH2

O

OH

OH

H

C

O

(CH2)14 CH3

*

CH2

C

CH2

OH H

O C

O

O C

O

(CH2)14 CH3

(CH2)14 CH3

CH2

C

CH2

O H

O C

O

OH

C

O

(CH2)16

(CH2)7CH CH (CH2)7 CH3

CH3*

CH2

C

CH2

O H

O C

O

O C

O

(CH2)14 CH3

(CH2)14 CH3

C

O

(CH2)14CH3

1-palmitomonoglyceride

1-oleo-2-stearodiglyceride

Triglyceride (tripalmitin)

1,3-dipalmitodiglyceride

Triglycerides chemical properties

Acidic hydrolysis (reaction reversible)

Basic hydrolysis (SAPONIFICATION, reaction irreversible)

+ +3H2O

CH2

CH

CH2 O H

O H

O HCH2

CH

CH2 O C

O C

O C

O

R1

O

R2

O

R3

C R1

HO

O

C R2

HO

O

C R3

HO

O

H+

Triglyceride fatty acids glycerol

+ +3NaOH

CH2

CH

CH2 O H

O H

O HCH2

CH

CH2 O C

O C

O C

O

R1

O

R2

O

R3CR3

ONa

O

CR1

ONa

O

CR2

ONa

O

Triglyceride salts of fatty acids glycerol

(soaps)

Enzymatic hydrolysis (reaction reversible) – a STEREOSELECTIVE reaction

Fatty acids of

carbons C1 i C3

+

CH2

CH

CH2 O H

O C

O H

O

R2

CH2

CH

CH2 O C

O C

O C

O

R1

O

R2

O

R3

CR3

OH

O

CR1

OH

O lipase

+ 2H2O

Triglycerides chemical properties

Triglyceride 2-monoglyceride

After ca. 5 minutes isomerization of a fatty acid group from C2 to C1 position occurs. Afterwards hydrolysis of the last FA group happens.

Hardening (hydrogenation)

Triolein Tristearin

(liquid plant fat) (solid fat: margarine)

The fastest hydrogenation occurs at position C-1 and C-3 and for fatty

acids rests containing four-three double bonds)

Negative side effects: trans fatty acids obtaining, changing of double bond

positions, polimerization of double bonds

CH2

C

CH2

O H

O C

O

O

C

O

(CH2)7

(CH2)7 CH

CH

C

O

CH

(CH2)7CH3

CH

(CH2)7

CH3

(CH2)7 CH CH

(H2C)7 CH3

CH2

C

CH2

O H

O C

O

O

C

O

(CH2)16

(CH2)16 CH3

C

O

(CH2)16 CH3

CH3

Ni+ 3H2

Triglycerides chemical properties

+NaOH

CH2

CH

CH2 O C

O C

O C

O

C15H31O

C17H33

O

C15H31

CH2

CH

CH2 O C

O C

O C

O

C17H35O

C17H33

OC17H29

+

CH2

CH

CH2 O C

O C

O C

O

C15H31O

C17H33

O

C17H29

CH2

CH

CH2 O C

O C

O C

O

C17H35O

C17H33

O

C15H31

substitute of cocoa butter

Triglycerides chemical properties

Transesterification – to make fats more nutritious and healthy, to introduce

omega-3 and omega-6 fatty acids to the structure of edible fats.

No unfavourable side effects during synthesis.

It is the source of structured fats.

CH2

CH

CH2

O

O

O

O

O

O

SHORT/MEDIUM CHAIN FATTY ACID

OMEGA-3 or -6 FATTY ACID

SHORT/MEDIUM CHAIN FATTY ACID

1-stearo-2-oleo-3-palmitin

Phospholipids - main components

Phosphoric acid

CH2 OH

C H

CH2 OH

HO

Glycerol

P

O

OH

OH

OH

Hydroxyl compounds:

choline

inosytol

CH2 CH

NH2

COOHOH

OHOH

OH

OH

OHOH

CH2 CH2 NH3OH+

CH2 CH2 N+

HO

CH3

CH3CH3

ethanolamine

serine

Phosphatidylserine (cephaline)

Phosphatidylethanolamine (cephaline)

Phosphatidylcholine (lecithine)

glycerophospholipids

Ester bond

CH2 CH

NH2

COOH

CH2 CH2 N+

CH3

CH3CH3

CH2 CH2 NH3

+

CH2

C

O

O

CH2 O

H

P

O

O

OH

C

O

C15H31

C

O

C17H35

R

*

Phospholipids

Their names depending on R:

glycerophospholipids

- phosphatidylcholine (-lecithine)

-phosphatidylethanolamine

(- cephaline)

*

CH2

C

O

O

CH2 O

HC

O

C17H35

C

O

C15H31

P

O

O

OH

CH2 CH2 N(CH3)3

+

Natural phospholipids are L i .

*

CH2

C

O

O

CH2 O

H

C

O

C15H31

P

O

O

C

O

C15H31

OH

CH2CH2H3N+

hydrophilic hydrophobic

Phospholipids

ester bond

phosphoester bond

plasmalogens

- form 10% of brain and muscles phospholipids

ethanolamine

Ether bond

Ethanolamine plasmalogen

R1 – rest of an alcohol

(mainly unsaturated)

R – rest of fatty acids *

C

C

O

O

CH2 O

H

P

O

O

OH

C

O

R

CH2 CH2 NH3

C CH R1

H

H

H

+

Phospholipids

They have anticancer properties.

sfingofosfolipidy

CH3(CH2)12

C CCH CH

NH2

OH

CH2 OHH

H CH3(CH2)12

C CCH CH

NH

OH

CH2 OHH

H C

O

R

-forms the myeline sheath around the axon of a neuron. It is essential for

the proper functioning of the nervous system.

Sphingosine Ceramide

Sphingomieline

Amide bond

Ester bond

R – rests of fatty acids

CH3(CH2)12

C CCH CH

NH

OH

CH2 OH

H C

O

R

P

O

OH

O R1

R1 – rests of

choline, serine,

ethanolamine

Phospholipids

Glycolipids

CH3(CH2)12

C CCH CH

NH

OH

CH2O

H

H C

O

(CH2)OH (CH2)21 CH3

C O

C

CC

C

H

HH

H

OH

OH

H OH

CH2 OH

Sugar, e.g. gluctose

Fatty acid,

e.g. Cerebronic acid

sphingosine

Cerebrosides - is a sphingolipid (ceramide) with a monosaccharide

such as glucose or galactose as polar head group.

gangliosides – a polar head group that is a

complex oligosaccharide.

Cerebrosides and gangliosides, collectively called

glycosphingolipids, are commonly found in the

outer leaflet of the plasma membrane bilayer, with

their sugar chains extending out from the cell

surface.

Steroids the group of naturally occuing compounds (plants, animals,

microorganisms)

All of them possess the 4-ring skeleton of STERAN (1,2-cyclopentano-

perhydrofenantrene).

10

5

1

4

2

3

8

7

9

6

13

14

12

1117

16

15

A B

C D

Steroids differ in: mutual arrangement of condensed rings– A/B, B/C and C/D,

degree of unsaturation, and type and length of side chains R1, R2 and R3.

Steran

sterols –steroids contaning -OH group in the C3 position

10

5

1

4

2

3

8

7

9

6

13

14

12

1117

16

15

R1

R2

R3

A B

C D

Common steroids’ skeleton

R1, R2 – mainly

CH3 groups

R3 – hydrocarbon

chain of different

length

Cholesterol and cholesterol esters

The hydroxyl at C-3 is hydrophilic; the rest of the

molecule is hydrophobic (amphipatic molecule);

also 8 centers of asymmetry

10

53

6

1317

CH3

CH3

CH2

CH2CH3

CH2

CHCH3

CH3

OH

xx

x

x

x

x

x

x

CH3

CH3

CH3CH2CH3

CH3 CH3

OH

CH3

CH3

CH3CH3

CH3 CH3

OH -Sitosterol (phytosterol, in plants) (to progesteron production)

Ergosterol, in fungi

(to vit. D2 production)

Functions:

-serves as a component of cell membranes (moderates

membrane fluidity)

-precursor to steroid hormones

-storage and transport – as cholesterol palmitate esters or

esters with linolenic acid

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 (low density lipoprotein) uptake

• degradation: only occurs in the liver

Lipid bilayer

Main components of lipid bilayer are: phospholipids, glycosphingolipids

and cholesterol (all lipids from 20 to 75%), proteins (ca. 50%), carbohydrates

The bilayer has LIQUID-CRYSTAL CHARACTER

In the liquid crystal state, hydrocarbon chains of

phospholipids are disordered and in constant motion

At lower temperature, a membrane containing a single

phospholipid type undergoes transition to a crystalline state

in which fatty acid tails are fully extended, packing is highly

ordered

Extracellular

matrix Glycoprotein

Carbohydrate

Plasma

membrane

Microfilaments

of cytoskeleton

Phospholipid

Cholesterol

Proteins

Cytoplasm

Glycolipid

Lipid bilayer

Cholesterol inserts into bilayer membranes with its hydroxyl group oriented toward the aqueous phase and its hydrophobic ring system is very close to fatty acid chains of phospholipids

Cholesterol regulates bilayer fluidity - interaction with the relatively rigid

cholesterol decreases the mobility of hydrocarbon tails of phospholipids

In the absence of cholesterol, such membranes would crystallize at

physiological temperatures

Prostaglandins-prostanoids (eicosanoids)

A prostaglandin is any member of a group of lipid compounds

that are derived enzymatically from fatty acids.

Every prostaglandin contains 20 carbon atoms, including a 5-

carbon ring.

They are local hormones and have a wide variety of actions:

- cause constriction or dilation in vascular smooth muscle cells

- cause aggregation or disaggregation of platelets

- sensitize spinal neurons to pain

- decrease intraocular pressure

- regulate inflammatory mediation

- regulate calcium movement

- control hormone regulation

- control cell growth

8

12 20

COOH1

Prostanoic acid

Linoleic acid (18:2)

COOH1

58

11 1420

COOH1

5

68

10

12 14

20

OH

OH

O

O 13

5 COOH1

15

20

OH

COOH16

11

9

13 15

20

O

O

OHOH

11

9

13 15

20

OH

OHOH

5 COOH1

PGH2

Arachidonic acid(20:4)

LTB4 (leukotriene)

6-keto-PGF1

(prostacyclin)

PGF2 (prostaglandin)

TXB2 (thromboxane)

14 16

21

OH

5 COOH1

O

11

9

OH

OH

acyclic compound

Cyclic compounds

Prostaglandins-prostanoids (eicosanoids)

CYCLOOXYGENASE aspirine inhibits it

Saponification number • the highest mass of a triglyceride, the lowest saponification number • defined as the number of milligrams of KOH needed to neutralize the fatty acids in

1 gram of fat

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

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

CH2

C

CH2

O H

O C

O

O C

O

C15H31

C15H31

C

O

H31C15+

CH2

CH

CH2 O H

O H

O H

CH31C15

O

O

K

CH31C15

O

O

K

CH31C15

O

O

K+ 3 KOH

806 g tripalmitin - 3 . 56 g KOH

1 g - x

x = 0,208 g = 208,4 mg

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 (older fats have lower iodine numbers)

+

CH2

C

CH2

O H

O C

O

O

C

O

(CH2)7 CH CH

(CH2)7

CH3

(CH2)7

CHCH

CH2

CHCH

CH2

CHCH

CH3

C15H31

4I2

CH2

C

CH2

O H

O C

O

O

C

O

(CH2)7 CH CH (CH2)7 CH3

(CH2)7

CHCH

CH2

CHCH

CH2

CHCH

CH3

C15H31

I I I I I I

I I

dioksan

854 g glyceride - 4 . 254 g iodine

100 g - x

x = 119,9 g

1. The compound given below, in which R1 and R2 are rests of fatty acids, is called:

O P

O

O

CH

CH2

OC

O

R2O C

O

R3CH

2

O

CH2

CH2

N(CH3)3

+

_A. α-lecithin

B. α-cephalin

C. Prostaglandin

D. β-cephalin

2. The following trigliceride contains rests of:

CH2

CH

CH2

O

O

O

C

O

C

O

C

O

C17H35

C17H33

C15H31

A. saturated fatty acids only

B. unsaturated fatty acids only

C. 2 saturated rests and 1 unsaturated

D. 2 unsaturated rests and 1 saturated

3. Complete the missing organic compounds:

CH2OH

CHOH

CH2OH

+ .........................1

CH2

CH

CH2

O

O

O

C

C

C

O

O

OC17H33

C17H33

C17H33

+ 3H2O

C17H35COOH + NaOH ......................... + H2O2.

3

C17H33COOH + H2

Ni .........................3.

A. 1- C17H33COOH, 2 - C17H35COONa, 3 - C17H35COOH

B. 1- C17H35COOH, 2 - C17H35COONa, 3 - C17H31COOH

C. 1- C17H33COOH, 2 - C17H35CONa, 3 - C17H31COOH

D. 1- C17H31COOH, 2 - C17H35CONa, 3 - C17H35COOH