LIPIDS(2)

Prepared By: Msc. Najat Hamed

Faculty of Pharmacy
Biochemistry
Academic year 2013-2014

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II- COMPOUNDS LIPIDS

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 PHOSPHOLIPIDS
 Phospholipids are the main lipid constituents of the
biological membranes.
 Phospholipids (PL) are lipids containing, in addition
to F.A and an alcohol, phosphoric acid and
nitrogenous base.
 PL are the major components of Plasma membranes.
 According to the alcohol, they are subclassified into:
1. Glycerophospholipids: the alcohol is glycerol.
2. Sphingophospholipids: the alcohol is sphingosine.
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 BIOLOGIC MEMBRANES

 Membranes are complex structures composed of lipids, proteins

and carbohydrates.
 About 35-40 % of dry weight lipid, 55-60 % of dry weight protein,
and 1-10 % of dry weight carbohydrates.
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 Phospholipids are the main lipid in membranes.
LIPID BILAYER OF MEMBRANES
PHOSPHOGLYCERIDES ARE THE MAJOR
COMPONENTS OF CELL MEMBRANES.

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 GLYCEROPHOSPHOLIPIDS
(PHOSPHOGLYCERIDES)

 They include the following main classes:

1. Phosphatidic acid
2. Cardiolipins
3. Lecithins
4. Cephalins
5. Plasmalogens

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PHOSPHOLIPIDS ARE AMPHIPATHIC:
POLAR HEAD AND NON-POLAR TAIL

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 PHOSPHOLIPIDS
 This is a simple representation of a phospholipid,
 the yellow structure represents the hydrophillic or
water loving section of the phospholipid.
 The blue tails represent the hydrophobic or water
fearing end of the Phospholipid.

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 COMMON MEMBRANE
PHOSPHOLIPIDS
CH3

NH3 NH3 H3C N CH3

CH2 CH2 COO CH2

H CH2 CH2 CH2

O O O O

O P O O P O O P O O P O

O O O O
H H H H
H2C C CH2 H2C C CH2 H2C C CH2 H2C C CH2

O O O O O O O O

O C C O O C C O O C C O O C C O

R1 R2 R1 R2 R1 R2 R1 R2

Phosphatidic Phosphatidylethanolamine
Phophatidylethanolamine Phosphatidylserine
Phophatidylserine Phosphatidylcholine
Phophatidylcholine 9
acid (Cephalin) (Lecithin)
 LECITHINS
 Lecithins consist of phosphatidic acid and choline, so
lecithins are sometimes called phosphatidyl choline.
 The choline base is esterified to the phosphate group.

+
CH2 O OC.R1 HO CH2 CH2 N (CH3)3
Phosphatidic Choline
acid CH O OC.R2

O
+
CH2 O P O CH2 CH2 N (CH3)3
OH 10
Lecithin
 SPHINGOPHOSPHOLIPIDS
 They are phospholipids containing sphingosine (complex amino
alcohol) instead of glycerol
 Sphingomyelin found in myelin sheath of nerves

Phosphate Choline
O
CH2 O P O CH2 CH2 N+ (CH3)3
CH2 OH
OH
CH NH OC.R1 CH NH OC.R1
CH OH CH OH Fatty acid
CH Sphingosine (Acyl radical)
CH
CH CH
(CH2)12 (CH2)12
CH3 CH3 11

Ceramide Sphingomyelin
 SPHINGOLIPIDS
Based on sphingosine (a base) instead of glycerol
OH

OH

sphingosine NH 2

R long chain hydrocarbon

HO

NH 2 attach fatty acid here

12
OH attach polar head group here
 GLYCOLIPIDS
 They are conjugated lipids that contain carbohydrates.
 They are esters of F.A with alcohol + carbohydrate
radical:
 The carbohydrate is usually galactose; so they are
called galactolipids
 All glycolipids contain sphingosine, so they are also
called sphingolipids
 They are present mainly in brain (cerebrum ) and so
called cerebrosides
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 TYPES OF GLYCOLIPIDS
1. CEREBROSIDES:
 They consist of: sphingosine + F.A. + Galactose or
rarely glucose. Found in neuronal membranes
2. GANGLIOSIDES:
 In gangliosides, the carbohydrate is more complex.
 Gangliosides are present in nervous tissues in high
concentration.

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HO R GLYCOLIPIDS
O

NH R'

O SUGAR polar head is a sugar

beta linkage

Types of glycolipids:

1- Cerebrosides: Single sugar

2- Gangliosides: Oligosaccharide 15
 PROTEOLIPIDS
 These are conjugated lipids with protein.
 The lipid surrounds the protein, making the
molecule insoluble in water but soluble in fat-
solvents.
 The lipoproteins are arranged in the reverse
way, the proteins surround the non-polar lipids
and hence their solubility in water.

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 LIPOPROTEINS
Lipoproteins are Lipid transport particles
They are particles found in plasma that
transport lipids including triacylglycerols
and cholesterol.
The protein part is called apolipoprotein
(Apo).

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LIPOPROTEIN STRUCTURE

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 LDL MOLECULE

•Responsible for recognition

of particle by receptors

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 PLASMA LIPOPROTEINS
 Plasma Lipoproteins can be classified into:
 Chylomicrons (CM)
 Very low density lipoproteins (VLDL or pre-
lipoproteins)
 Low density lipoproteins (LDL or -
lipoproteins)
 High density lipoproteins (HDL or  -
lipoproteins)
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 Chylomicrons

Very low density

Composition Lipoprotein (VLDL)

Low density
of
Lipoprotein (LDL)

Lipoproteins High density

Lipoprotein (HDL)

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 Plasma Lipoproteins

Triacylglycerol transport:
Chylomicrons: TG of dietary origin
VLDL: TG of endogenous synthesis

Cholesterol transport:
LDL: Mainly free cholesterol
HDL: Mainly esterified cholesterol

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 Composition and properties of human lipoproteins
Lipoprotein Density Diameter Protein % Phospholipid % TAG% Cholesterol
%
class (g/mL) (nm)

HDL (Alpha) 1.063-1.21 5 – 15 33 29 8 15

LDL (Beta) 1.019 – 1.063 18 – 28 25 21 4 40

0.95 – 1.006 30 - 80 10 18 50
VLDL 13

Chylomicrons < 0.95 100 - 500 1-2 7 84 ---

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STEROIDS
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 STEROIDS
 Steroids are large and very important compounds
usually associated with lipid. They all contain a ring
system called cyclo-pentano-perhydro-phenanthrene
ring (CPPP); also called steroid nucleus.
12 17
11 13 16
C D
14 15

1 10 9
2 8
A B
3 5 7
4 6
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Steroid Nucleus
STEROID NUMBERING SYSTEM

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12 17
11
19 C 13 D 16
1
2 9 14 15
10 8
A B
3 5 7
4 6 26
CHEMISTRY OF STEROLS (STEROIDAL
COMPOUNDS)
1. Structure
a. made up of multiple rings
b. Steroid nucleus
2. Sterols in foods
a. Plants and animal foods contain sterols
b. Cholesterol only found in animal products
Eggs and organ meats very high sources (eggs = 250 mg)

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 STEROIDS
 Steroids are compounds containing a steroid ring
(steroid nucleus).
 Steroids include:

 I- Sterols e.g. Cholesterol

 II- Bile acids and bile salts e.g. Cholic acid.

 III- Steroid hormones

e.g. Estrogen , Testosterone and Cortisol.

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 CHEMISTRY OF STEROLS
(STEROIDAL COMPOUNDS) (CONT)

@ 3. Role of sterols
a. Bile acids
1. Fat metabolism
2. Polar and non-polar groups
b. Sex hormones
1. Estrogen
2. testosterone
c. Adrenal hormones
1. Corticosteroids
d. Vitamin D 29
 CHOLESTEROL
 Cholesterol is the most important animal sterol
(zoosterol).
 Chemical structure:

 It contains steroid nucleus.

 It contains 27 carbon atoms

 At C3, there is hydroxyl group and so it is an alcohol.

 There is a double bond between C5-C6 (5).

 There are two methyl groups at C10 & C13.

 There is a side chain at C17. 30

 CHOLESTEROL
21 22
23 26
18 20
CH3
25
17 24
19 13 27
CH3
10
3 5
6

HO Structure of cholesterol 31
 DISTRIBUTION
OF CHOLESTEROL
 Cholesterol is found in every cell membrane, it is
present in large amounts in certain tissues; e.g.
1. Suprarenal cortex
2. Liver
3. Kidney
4. Ovaries and Testis
5. Brain

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 SOURCES OF
CHOLESTEROL
 Exogenous sources:
From the diet; e.g. egg yolk, liver, brain.
 Endogenous sources:

 Every cell can synthesize its own cholesterol.

Cholesterol is synthesized inside the body from acetyl-
CoA.
 Blood cholesterol is mainly synthesized in the liver.

 Normal level of cholesterol in blood is

about 150 – 200 mg/dl. 33

 FUNCTIONS OF
CHOLESTEROL
1. Cholesterol is present in the plasma membrane
of many cells
2. Cholesterol is the precursor of all the steroid
hormones
3. Cholesterol is the precursor of vitamin D3
(cholecalceferol)
4. Cholesterol is the precursor of bile acids and
bile salts
5. Cholesterol is important for plasma
lipoproteins (e.g. LDL and HDL)
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COMPOUNDS DERIVED FROM
CHOLESTEROL

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COMPOUNDS DERIVED FROM
CHOLESTEROL

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 CHOLESTEROL AND
ATHEROSCLEROSIS
Atherosclerosis means focal accumulation of lipid
(athere = gruel) and thickening of arterial intima (sclerosis =
hardening)
Coronary artery atherosclerosis is the principal cause of coronary
artery disease (CAD) and is the single largest killer of both men
and women in the world.
Cholesterol is related to atherosclerosis and coronary heart disease
especially in cases of hypercholesterolemia.

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 EICOSANOIDS
 Eicosanoids are compounds derived from eicosa- (20-C)
polyenoic fatty acids.
 They include:
1. Prostaglandins (PG)
2. Prostacyclins (PGI)
3. Thromboxanes (TX)
4. Leukotrienes (LT) and
5. Lipoxins
 The term “prostaglandins” is often used loosely to
include all Eicosanoids 38
 EICOSANOIDS
 Local hormones, key mediators of inflammation, pain,
and spasm.

 Synthesized in our cells from (PUFA arachidonic acid

(20:4).

COOH

CH 3

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 IMPORTANCE OF
EICOSANOIDS
 The prostaglandins, thromboxanes and
leukotrienes are products of arachidonic acid
metabolism.
 Many of these substances are involved in
important physiologic functions sometimes in a
hormone like manner, some of them we do not
know its role.
 Prostaglandins have different pharmachological
and biological functions.
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 FUNCTIONS OF
EICOSANOIDS
Physiological Functions:

 1- Important for normal healthy gastric tissue

 2- Important for normal ovarian and uterine
function
 3- Important for platelet homeostasis
 4- Important for smooth muscle regulation
(Contraction and relaxation)
 5- Important for nerve and brain function
 6- Important for normal renal function
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 FUNCTIONS OF EICOSANOIDS
Pathological Functions:

They are Mediators of inflammation, fever, pain and

allergy

 Clinical applications
Drugs are now available that contain PG-derivatives to:
1. Induce labor or abortion
2. Treat gastric ulcers
3. Treat impotence in men (Viagra-like).
These drugs are used as injections or topically (Gels, Pessaries)
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 CAROTENOIDS
 Carotenoids are colored compounds, yellow to red,
which are found associated with fats in nature. They are
insoluble in water and soluble in fats and fat solvents.
 Carotenoids include:
 Carotenes
 Xanthophylls.
 Carotenoids are precursor of vitamin A.
 Carotenoids act as anti-oxidant and protect
from malignancy.

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