LIPIDS - Warszawski Uniwersytet Medyczny · 2018. 11. 12. · Lipids 1. Simple lipids: Triglycerides (Fats & Oils), Waxes 2. Complex lipids Glycerophospholipids Steroids (Cholesterol

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

1. Store energy: fat cells

2. Chemical messengers: find in nerve fibers and hormones.

3. Parts of membranes: insoluble in water

Lipids

4. Precursors of hormones (steroids

and prostaglandins)

Functions

Thermal blanket

LipidsThere are 2 types of lipids; •those that contain the structural component of a fatty acid; and

•those that contain the structural component of a four member steroid molecule.

Lipids

1. Simple lipids:

Triglycerides (Fats & Oils), Waxes

2. Complex lipids Glycerophospholipids

Steroids (Cholesterol & steroid hormones)

3. Eicosanoids

Store energy, insulation

Cell

membrane

Chemical messenger

Cell membrane

Pain, fever, inflammation

Sphingolipids

Lipids with fatty acids

Lipids without fatty acids

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)

Lipids can be categorized as:

1. Hydrolyzable lipids can be converted into small

molecules by aqueous hydrolysis.

Lipids

Lipids can be categorized as:

2. Nonhydrolyzable lipids cannot be cleaved into smaller

molecules by aqueous hydrolysis.

Lipids

Hydrolysis: reaction with water.

(breaking a bond and adding the elements of water)

RCOR'

O

RC-OH

O

H-OR'

An alcoholA carboxylic acidAn ester

+ H2O +Heat

H+ or enzyme

Hydrolysis

Most hydrolyzable lipids contain an ester.

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

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 COOHn - carbon atoms in a molecule

COOH

COOH

COOH

COOH

Stearic acid (18:0)

(mp 70°C)

Oleic acid (18;1)

(mp 16°C)

Linoleic acid (18:2)

(mp-5°C)

Linolenic acid (18:3)

(mp -11°C)

Nomenclature of fatty acids

SATURATED FATTY ACIDS

Common name Systematic name Formula

C4:0 Butyric Butanoic acid C3H7COOH

C6:0 Caproic acid Hexanoic acid C5H11COOH

C8:0 Caprylic acid Octanoic acid C7H15COOH

C10:0 Capric acid Decanoic acid C9H19COOH

C12:0 Lauric acid Dodecanoic acid C11H23COOH

C14:0 Myristic acid Tetradecanoic acid C13H27COOH

C16:0 Palmitic acid Hexadecanoic acid C15H31COOH

C18:0 Stearic acid Octadecanoic acid C17H35COOH

C20:0 Arachidic Eicosanoic acid C19H39COOH

C24:0 Lignoceric acid Tetracosanoic acid C23H47COOH

C16:0 Palmitic acid (C15H31COOH)

Structural formula of palmitic acid

CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 COOH

CH3(CH2)14COOH

Condensed structural formula of palmitic acid

Skeletal formula of palmitic acid

C

O

OH

Fatty acids

Fatty acids are:

• Long-chain unbranched carbon

attached to a carboxyl group (-COOH).

• Typically 12-20 carbon atoms.

• They have an even number of C atoms.

• Insoluble in water.

COOH

COOH

COOH

COOH

Stearic acid (18:0)

(mp 70°C)

Oleic acid (18;1)

(mp 16°C)

Linoleic acid (18:2)

(mp-5°C)

Linolenic acid (18:3)

(mp -11°C)

COOH

COOH

COOH

COOH

Stearic acid (18:0)

(mp 70°C)

Oleic acid (18;1)

(mp 16°C)

Linoleic acid (18:2)

(mp-5°C)

Linolenic acid (18:3)

(mp -11°C)

Cis

Hydrolyzable lipids are derived from fatty acids.

Fatty acids

nonpolar portion = hydrophobic

polar portion = hydrophillic

CH3(CH2)14COOH (palmitic acid)

Hydrophobic portion is much bigger than hydrophilic portion.

Insoluble in water

Saturated and unsaturated Fatty acids

Saturated fatty acids have no double bonds in their long hydrocarbon

chains.

COOH

COOH

COOH

COOH

COOH

Packed together

They are solids at room temperature.

Stearic acid: CH3(CH2)16COOH

Unsaturated fatty acids have 1 or more double bonds (generally cis) in their

long hydrocarbon chains.

Saturated and unsaturated Fatty acids

COOH

COOH

COOH

COOH

COOH

They can not pack together

They are liquids at room temperature.

Oleic acid: CH3(CH2)7CH=CH(CH2)7COOH

Kinks

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

n (Δ) designation:

In biochemistry:

ω designation

Carbon atom numbering starts from COOH group

Carbon atom numbering starts from CH3 group

ω = omega

Δ = delta

• The human body is capable of synthesizing most fatty acids

from carbohydrates or other fatty acids.

• Humans do not synthesize sufficient amounts of fatty acids

that have more than one double bond.

• More than one double bond fatty acids are called essential

fatty acids and they must be provided by the diet.

Fatty acids

Linoleic acid Linolenic acid

(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

Linoleic acid is called an omega-6 acid, because of the

position of the first C=C in the nonpolar chain.

Essential Fatty acids

Omega-n acids n: the position of the first double bond

carbon atom numbering startsfrom CH3 group

Linolenic acid is called an omega-3 acid, because of the

position of the first C=C in the nonpolar chain.

Essential Fatty acids

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

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

Fatty acids

• Common medium-chain saturated fatty acids:

C5H11COOH caproic acid (hexanoic acid)

C7H15COOH caprylic acid (octanoic acid)

C9H19COOH capric acid (decanoic acid)

CH36

CH25

CH24

CH23

CH22

COOH1 caproic acid

➢ liquid (C1 to C6), solid (from C7)

• C3H7COOH butyric acid (butanoic acid) – short chain FA

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, dihydroxystearicacid, 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

MonoUnsaturated fatty acidsMUFA

• 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.

• C18H34O2

• C17H33 COOH

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 (Δ9)

Chemical formula

Unsaturated fatty acids

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

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

cis

linoleic acid

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

Chemical formula

C18H32O2

C17H31COOH

PolyUnsaturated fatty acidsPUFAs

• Polyenoic acid (polyunsaturated, tetranoic acid)

COOH

CH3

Arachidonic acid 20:4 (Δ 5,8,11,14)

PUFAs are fatty acids that contain more than one double bond in their backbone

CH3-(CH

2)7-CH=CH-(CH

2)7-COOH

UNSATURATED FATTY ACIDS

Oleic acid 18:1 ω-9 cis Δ9

Elaidic acid 18:1 ω-9 trans Δ9

Linoleic acid (LA) 18:2 ω-6 cis Δ 9,12

γ-Linolenic acid (GLA) 18:3 ω-6 cis Δ6,9,12

α-Linolenic (ALA) 18:3 ω-3 cis Δ 9,12,15

Arachidonic acid 20:4 ω-6 cis Δ 5,8,11,14

Eicosapentaenoic acid (EPA) 20:5 ω−3 cis Δ 5,8,11,14,17

Docosahexaenoic acid (DHA) 22:6 ω−3 cis Δ 4,7,10,13,16,19

COOH18 9

COOH

18

9

CH3-(CH

2)7-CH=CH-(CH

2)7-COOH

COOH9

18

12 CH3-(CH

2)4-(CH=CH-CH

2)2-(CH

2)6-COOH

COOH

9

18

12 6 CH3-(CH

2)4-(CH=CH-CH

2)3-(CH

2)3-COOH

COOH18 9

CH3-CH

2-(CH=CH-CH

2)3-(CH

2)6-COOH

COOH8

20

11 514 CH3-(CH

2)4-(CH=CH-CH

2)4-(CH

2)2-COOH

COOH820 11 51417 CH

3-CH

2-(CH=CH-CH

2)5-(CH

2)2-COOH

4

COOH

19 101316 722 CH3-CH

2-(CH=CH-CH

2)6-CH

2-COOH

Comparison of melting points

Melting Points of Saturated vs. Unsaturated Fatty Acids:

the unsaturated fatty acids have lower melting points than the

saturated fatty acids.

The molecular structure allows many fatty acid molecules to be rather closely "stacked" together. Close intermolecular interactions result in relatively high melting points.

The introduction of one or more doublebonds in the hydrocarbon chain inunsaturated fatty acids results in one ormore "bends" in the molecule. Thesemolecules do not "stack" very well. Theintermolecular interactions are muchweaker than saturated molecules. As aresult, the melting points are much lowerfor unsaturated fatty acids.

Comparison of melting pointsMelting Points of Saturated vs. Unsaturated Fatty Acids:

the unsaturated fatty acids have lower melting points than the

saturated fatty acids.

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.)

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.

Long-chain alcohol Fatty acidEster bond

Waxes

Wax is an ester of saturated fatty acid and long chain alcohol.

Acid

Long-chain alcohol

Because of their long nonpolar C chains, waxes are very hydrophobic.

Waxes

Beeswax(myricyl palmitate)

CH3(CH2)14 C

O

O(CH2)29CH3

hydrophobic

regionhydrophobic

region

They form protective coatings:

- In plants, they help prevent loss of water and damage from pests.

- In humans and animals, provide waterproof coating on skin and fur.

Beeswax CarnaubaCoating

Jojoba

Lanolin from wool lotions

Waxes

Hydrolysis reaction: like other esters, waxes are hydrolyzed.

Heat

Sodium soaps1,2,3-Propanetriol

(Glycerol; glycerin)A triglyceride

( a triester of glycerol)

+saponification

+

CH2 OCR

CH2 OCR

CHOH

CH2 OH

CH2 OH

RCOCH 3 NaOH 3 RCO-Na

+O

O

O

O

Soaps

Hydrophobic part: nonpolar

Hydrophilic part: polar (remains in contact with environment)

a soap is

a salt of

a fatty acid

Soaps

++

+

+

+ +

+

+

+

+ +

+

Na+

fat

waterO

HH

Soaps solution

- a micelle

(emulsion type o/w)

Organization of soaps

molecules in water

When soap is mixed with dirt (grease, oil, and …), soap

micelles “dissolve” these nonpolar, water-insoluble molecules.

Soaps

soft

-potassium soaps, e.g shampoo,

shaving soaps, liquid soaps

C17H35COO-K+

Soaps

hard

-sodium soaps

e.g. soap bar

C17H35COO-Na+

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-

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

These substances are usually alkylbenzenesulfonates

Polar sulfonate (of detergents) is less likely than the

polar carboxylate (of soap) to bind to calcium and other ions found

in hard water.

Simple lipids

• Glycerides (fats and oils)– Glycerol

– Esters of glycerol - monoglycerides, diglycerides and triglycerides

• Waxes – simple esters of long chain alcohols and long chainfatty 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

1-stearoyl-2,3 linoleoyl glyceride

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

Types of Fatty Acid Lipids

Phospholipids

phospate phospate

Phospholipids

Phospholipids are lipids that contain a P atom.

Two common types:

They are the main component of most cell membranes.

Structurally, they resemble a triacylglycerol, except the third fatty

acid has been replaced with a phosphodiester bonded to an

alcohol.

Phospholipids

Amino alcohol

Fatty acid

Fatty acid

1. Phosphoacylglycerols (glycerophospholipids):

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

1. Phosphoacylglycerols:

Phospholipids

CholineEthanolamine

Phosphatidylserine (cephaline)

Phosphatidylethanolamine (cephaline)

Phosphatidylcholine (lecithine)

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:

1. Phosphoacylglycerols:

- 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

1. Phosphoacylglycerols:

2 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.

Ethalomine

Serine

Choline

Inositol

Phospholipids

3. Sphingolipids (Sphingomyelins): They differ in two ways:

1. They do not contain a glycerol backbone, they have a

sphingosine backbone instead.

sphingosine

2. They do not contain an ester; their single fatty acid is bonded to

the backbone by an amide bond.

Phospholipids

3. Sphingolipids (Sphingomyelins)

The myelin sheath, the coating that surrounds nerve cells, is rich in

sphingomyelins.

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

3. Sphingolipids (Sphingomyelins)

Phospholipids

Sphingomieline

3. Sphingolipids (Sphingomyelins)

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.

Component Structures of Some Important Membrane Lipids

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

Prostaglandins and Leukotrienes are two types of

eicosanoids (20 C atoms derived from the fatty acids).

Eicosanoids

- All eicosanoids are very potent compounds, which are not

stored in cells, but rather synthesized in response to external

stimulus.

- Unlike hormones they are local mediators, performing their

function in the environment in which they are synthesized.

Prostaglandins

Prostaglandins are responsible for inflammation.

- Aspirin and ibuprofen relieve pain and inflammation by blocking

the synthesis of these molecules.

- Prostaglandins also decrease gastric secretions, inhibit blood

platelet aggregation, stimulate uterine contractions, and relax

smooth muscles.

- There are two different cylcooxygenase enzymes

responsible for prostaglandin synthesis called COX-1 and

COX-2.

Prostaglandins

COX-1 is involved in the usual production of

prostaglandins.

COX-2 is responsible for additional prostaglandins in

inflammatory diseases like arthritis.

- Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and

ibuprofen inactivate both COX-1 and -2, but increase risk for

stomach ulcer formation.

- Drugs sold as Vioxx, Bextra, and Celebrex block only the

COX-2 enzyme without affecting gastric secretions.

Leukotrienes are molecules that contribute to the asthmatic

response by constricting smooth muscle of the lung.

Asthma is characterized by chronic inflammation, so inhaled

steroids to reduce this inflammation are commonly used.

New asthma drugs act by blocking the synthesis of

leukotriene C4, which treat the disease instead of just the

inflammation symptoms.

Leukotrienes

Steroids have:

• A steroid nucleus which is

4 carbon rings.

• Attached groups that make the different types of compounds.

• No fatty acids.

Steroids

(steroid nucleus)

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

Cholesterol:

• Is the most abundant steroid in the body.

• Insoluble in water (need a water soluble carrier).

• Has methyl CH3- groups, alkyl chain, and -OH

attached to the steroid nucleus.

CH3

CH3CH3

CH3

HO

CH3

Cholesterol

Triacylglycerols

Lipoproteins

Transporting lipids through the bloodstream to tissues where they are stored,

Used for energy, or to make hormones.

Spherical particles

Polar surface and nonpolar inner

Water-soluble form of lipids

(soluble in blood)

Lipoproteins

VLDL: very-low-density lipoprotein

LiverFat storage

cells

Heart and

muscles

LDL

VLDL

HDLEnergyIntestine

and

elimination

Triglycerides and Cholesterol

LDL: low-density lipoprotein (bad Cholesterol) Cholesterol

Chylomicrons Triglycerides and Cholesterol

HDL: high-density lipoprotein (good Cholesterol) Cholesterol

Recommended levels are: HDL > 40 mg/dL, LDL < 100 mg/dL, total serum cholesterol < 200 mg/dL.

1. Sex hormones

2. Adrenal Cortical Steroids

Steroid Hormones

A hormone is a molecule that is synthesized in one part of an

organism, which then elicits a response at a different site.

Two types of steroids hormones:

Estrogens & progestins in females

Androgens in males

Sex Hormones

The estrogens estradiol and estrone control development of secondary

sex characteristics, regulate the menstrual cycle, and are made in the

ovaries.

Estrogens (Female Sex Hormones):

Sex Hormones

Progestins (Female Sex Hormones):

The progestin progesterone is called the “pregnancy hormone”; it is

responsible for the preparation of the uterus for implantation of a fertilized

egg.

Sex Hormones

Androgens (Male Sex Hormones):

Testosterone and Androsterone are androgens made in the testes.

They control the development of secondary sex characteristics in males.

Adrenal Cortical Steroids

Aldosterone regulates blood pressure and volume by controlling the

concentration of Na+ and K+ in body fluids.

Cortisone and cortisol serve as anti-inflammatory agents, which also

regulate carbohydrate metabolism.

aldosteronecortisone

cortisol

They are organic compounds required in small quantities for normal

metabolism.

Vitamins are either water soluble or fat soluble.

The four fat-soluble vitamins (A, D, E, and K) are lipids and

nonpolar.

Excess vitamins are stored in adipose cells to be used when needed.

Vitamins

They must be obtained from the diet (our cells cannot synthesize them).

They are found in fruits, vegetables, fish, liver, and dairy products.

Vitamins

It is found in liver, fish, and dairy products, and is made from β-carotene

(the orange pigment in carrots).

It is needed for vision and for healthy mucous membranes.

Vitamin A deficiency causes night blindness and dry eyes and skin.

Vitamin A

Vitamins

Vitamin D

Vitamin D can be synthesized from cholesterol. It is produced

in the skin on exposure to UV radiation

It can be obtained in the diet from many foods, especially milk, and

helps regulate Ca and P metabolism.

Is necessary for normal bone growth and function.

A deficiency of vitamin D causes rickets (bone malformation).

Vitamins

Vitamin E

Vitamin E is an antioxidant, protecting unsaturated side chains in

fatty acids from unwanted oxidation.

Deficiency of vitamin E causes numerous neurological problems,

although it is rare.

Vitamin K

Vitamin K regulates the synthesis of clotting proteins (prothrombin),

and deficiency of this leads to excessive or fatal bleeding.

Vitamins

Schematic Diagram of a Cell Membrane

The phospholipid bilayer with embedded cholesterol and protein

molecules.

Short oligosaccharide chains are attached to the outer surface.

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

matrixGlycoprotein

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

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

Thank You