Transcript What Are Lipid?

Lipids and Membranes
What Are Lipid?
lipids are a family of substances that are
insoluble in water but soluble in nonpolar
solvents and solvents of low polarity
( diethyl ether).
Lipid
 Lipids: (Greek: lipos, fat)
 Are substances of biological origin

Soluble in organic solvents such as chloroform
and methanol
 Sparingly soluble, if at all, in water. Fats, oils,
 Certain vitamins and hormones, and most
nonprotein membrane components are lipids.
Lipids are fatty acids and their
derivatives, and substances related
biosynthetically or functionally to these
compounds.
Lipids play three major roles in human
biochemistry
(1) They store energy within fat cells
(2) they are parts of membranes that separate
compartments of aqueous solutions from each
other.
(3) they serve as chemical messengers.
I.Storage
An important use for lipids especially in animals
is the storage of energy.
● plants store energy in the form of starch.
● Animals (including humans) find it more
economical to use fats instead.
The reason is simple: The burning of fats
produces more than twice as much energy
(about 9 kcal/g) as the burning of an equal
weight of carbohydrates (about 4 kcal/g).
II.Membrane Components
The lack of water solubility of lipids is an important property
because our body chemistry is so heavily based on water.
Most body constituents, including carbohydrates and
proteins, are soluble in water. However, the body also
needs insoluble compounds for the membranes that
separate compartments containing aqueous solutions,
whether they are cells or organelles within the cells. Lipids
provide these membranes.
Their water insolubility derives from the fact that the polar
groups they contain are much smaller than their alkane-like
(nonpolar) portions.
These nonpolar portions provide the water-repellent, or
hydrophobic, property.
III.Messengers
Primary messengers, such as steroid hormones,
deliver signals from one part of the body to
another part.
Secondary messengers, such as prostaglandins
and thromboxanes, mediate the hormonal
response.
we can classify lipids into four groups:
(1) simple lipids, such as fats and waxes;
(2) complex lipids;
(3) steroids; and
(4) prostaglandins, thromboxanes, and
leukotrienes.
What Are the Structure of
Triglycerides?
Animal fats and plant oils are
triglycerides.
Triglycerides are triesters of glycerol and
long-chain carboxylic acids called fatty acids
we saw that esters are made up of an alcohol
part and an acid part.
Fatty
acids
Fatty acid nomenclature
O
C15
C13
C11
C9
C7
C5
C3
C1
C6
C4
C2
C18
C16
C14
C12
C10
C8
C17
HO
O
C1
HO
C6
C4
C2
C3
C5
C7
C9
C11
C13
C18
C16
C14
C12
C10
C8
C
H15
C17
Common saturated fatty acids
common name
IUPAC name
melting point (Co)
12:0
laurate
dodeconoate
44
14:0
myristate
tetradeconoate
52
16:0
palmitate
hexadeconoate
63
18:0
stearate
octadeconoate
70
20:0
arachidate
eicosanoate
75
22:0
behenate
docosanoate
81
24:0
lignocerate
tetracosanate
84
Common unsaturated fatty acids
common name
IUPAC name
melting
point
(Co)
16:0
palmitate
hexadeconoate
63
16:1 D9
palmitoleate
cis-D9-hexadeconoate
-0.5
18:0
stearate
octadeconoate
70
18:1 D9
oleate
cis-D9- octadeconoate
13
18:2 D9,12
linoleate
cis-D9,12- octadeconoate
-9
18:3 D9,12,15
linolenate
cis-D9,12,15- octadeconoate
-17
20:0
arachidate
eicosanoate
75
20:4 D5,8,11,14
arachindonate
cis- D5,8,11,14-eicosatetraenoate
-49
These fatty acids, have certain things in common:
1- Fatty acids are practically all unbranched
carboxylic acids.
2- They range in size from about 10 to 20 carbons.
3- They contain an even number of carbon atoms.
4 - Apart from the -COOH group, they have no
functional groups, except that some do have
double bonds.
5 - In most fatty acids that have double bonds, the
cis isomers predominate.
 Only even-numbered acids are found in
triglycerides because the body builds these
acids entirely from acetate units and therefore
puts the carbons in two at a time.
 In triglycerides (also called triacylglycerols),
all three groups of glycerol are esterified.
Synthesis of saturated fatty acids via Fatty Acid
Synthase II in E. coli
Synthesis of unsaturated fatty acids via anaerobic desaturation
Synthesis of unsaturated fatty acids via anaerobic desaturation
Synthesis of unsaturated fatty acids via anaerobic
desaturation
• Triglycerides are the most common lipid
materials, although mono and diglycerides are not
infrequent. In the latter two types, only one or two
-OH groups of the glycerol are esterified by fatty
acids .
• Triglycerides are complex mixtures. Although
some of the molecules contain three identical
fatty acids, in most cases two or three different
acids are present.
• The hydrophobic character of triglycerides is
caused by the long hydrocarbon chains. The ester
groups (-C-O- ), although polar them-selves, are
buried in a nonpolar environment, which makes
the triglycerides insoluble in water.
What Are Some Properties of
Triglycerides?
A. Physical State
Fat A mixture of triglycerides containing a high proportion of longchain, saturated fatty acids
oil A mixture of triglycerides containing a high proportion of longchain, unsaturated fatty acids or short-chain, saturated fatty acids.
 With some exceptions, fats that come from animals are generally
●solids at room temperature, ●liquids. from plants or fish.
 Liquid fats are often called oils
What is the structural difference between solid fats and liquid oils?
In most cases, it is the degree of unsaturation.
• Solid animal fats contain mainly saturated
fatty acids, Note that even solid fats contain
some unsaturated acids
• Vegetable oils contain high amounts of
unsaturated fatty acids and that liquid fats
contain some saturated acids.
Table 21.1 shows the average fatty acid content
of some common fats and oils.
Table 21.1
Average Percentage of Fatty Acids of Some Common Fats and Oils
Saturated
Lauric
Myristic
Palmitic
Unsaturated
Stearic
Oleic
Linoleic
Linolenic
Other
Animal Fats
Beef tallow
-
Butter
2.5
6.3
27.4
14.1
49.6
2.5
-
0.1
11.1
29.0
9.2
26.7
3.6
-
17.9
Human
-
2.7
24.0
8.4
46.9
10.2
-
78
Lard
-
1.3
28.3
11.9
47.5
6.0
-
5.0
18.0
10.5
2.3
7.5
-
16.3
Vegetable ofls
Coconut
45.4
-
Corn
-
1.4
10.2
3.0
49.6
34.3
-
1.5
Cottonseed
-
1.4
23.4
1.1
22.9
47.8
-
3.4
Linseed
-
-
6.3
2.5
19.0
24.1
Olive
-
-
6.9
2.3
84.4
4.6
-
1.8
Peanut .
-
-
8.3
3.1 .
56.0
26.0
-
6.6
Safflower
-
-
6.8
18.6
70.1
3.4
1.1
3.6
2.7
Soybean
Sunflower
0.2
-
0.1
-
-
9.8
2.4
28.9
52.3
5.6
2.2
25.1
66.2
47.4
-
0.7
-
●Some unsaturated fatty acids (linoleic and
linolenic acids) are called essential fatty acids
because the body cannot synthesize them from
precursors; they must, therefore, be consumed as
part of the diet.
●Although most vegetable oils contain high
amounts of unsaturated fatty acids, there are
exceptions.
Coconut oil, for example, has only a small amount
of unsaturated acids. This oil is a liquid not
because it contains many double bonds, but
rather because it is rich in low-molecular-weight
fatty acids (chiefly lauric acid).
• Oils with an average of more than one double
bond per fatty acid chain are called
polyunsaturated.
Pure fats and oils are colorless, odorless, and tasteless.
This statement may seem surprising because we all
know the tastes and colors of such fats and oils as
butter. and olive oil. The tastes, odors, and colors are
caused by small amounts of other substances dissolved
in the fat or oil
B. Hydrogenation.
We learned that we can reduce carbon-carbon
double bonds to single bonds by treating
them with hydrogen and a catalyst. It is,
therefore, not difficult to convert unsaturated
liquid oils to solids.
◊ This hydrogenation is carried out on a large scale to
produce the solid shortening solid in stores under such
brand names as Crisco, Spry, and Dexo.
◊ In making such products, manufacturers must be
careful not to hydrogenate all of the double bonds,
because a fat with no double bonds would be too solid.
Partial, but not complete, hydrogenation results in a
product with just the right consistency for cooking.
 Margarine is also made by partial hydrogenation of
vegetable oils. Because less hydrogen is used,
margarine contains more unsaturation than fully
hydrogenated shortenings.
C. Saponification
• Soap is the base-promoted hydrolysis of fats
and oils producing glycerol and a mixture of
fatty acid salts
• it has been used for thousands of years, and
saponification is one of the oldest known
chemical reactions
soaps are soluble sodium or potassium
salts of carboxylic acids
Hydrolysis of esters under basic
conditions to form an alcohol and the
salt of a carboxyli acid (carboxylates).
What Are the Structures of Complex
Lipids?
Complex lipids can be classified into two groups:.
 Phospholipids contain an alcohol, two fatty acids,
and a phosphate group.
There are two types:
o glycerophospholipids alcohol is glycerol
o sphingolipids, the alcohol is sphingosine .
 Glycolipids are complex lipids that contain
carbohydrates.
What Role Do Lipids Play in the
Structure of Membrane?
The complex lipids form the membranes around
body cells and around small structures inside the
cell's. (organelles.)
Unsaturated fatty acids are important components of
these lipids.
Most lipid molecules in the bilayer contain at least
one unsaturated fatty acid.
The cell membranes separate cells from the external
environment and provide selective transport for
nutrients and waste products into and out of cells.
• These membranes are made of lipid bilayers.
• The hydrophobic tails point toward each
other, which enables them to get as far away
from the water as possible.
• the hydrophilic heads projecting to the inner
and outer surfaces of the membrane.
Cholesterol , another membrane component,
 positions the hydrophilic portion of the molecule
on the surface of the membranes and the
hydrophobic portion inside the bilayer.
 The unsaturated fatty acids prevent the tight
packing of the hydrophobic chains in the lipid
bilayer, thereby providing a liquid-like character
to the membranes.
This property of membrane fluidity is of extreme
importance because many products of the body's
biochemical processes must cross the membrane,
and the liquid nature of the lipid bilayer allows
such transport.
Protein molecules , (in the lipid
bilayer)
 are either suspended on the surface
(peripheral proteins) or
 partly or fully embedded in the bilayer
(integral proteins).
Others are thoroughly embedded, going
through the bilayer and projecting from
both sides.
The model, fluid mosaic model of membranes,
allows the passage of
 nonpolar compounds by diffusion, as these
compounds are soluble in the lipid membranes.
 polar compounds are transported either via
specific channels through the protein regions
or
active transport mechanism.
What Are
Glycerophosphospholipids?
The structure of glycerophospholipids
(phosphoglycerides) is very similar to that of fats.
 Glycerophospholipids are membrane components of
cells throughout the body.
 The alcohol is glycerol.
 Two of the three groups are esterified by fatty acids,
these fatty acids may be any long-chain carboxylic cids,
with or without double bonds.
 In all glycerophospholipids, lecithins, cephalins, and
phosphatidylinositols, the fatty acid on carbon 2 of
glycerol is always unsaturated.
• The third group is esterified not by a fatty acid,
but rather by a phosphate group,
• which is also esterified to another alcohol.
 If the other alcohol is choline , the
glycerophospholipids are called phosphatidylcholines (common name lecithin),
 If the other alcohol is ethanolamine or serine are
called cephalins,
 If the the alcohol inositol , is the phosphatidyli
nositols .
Name of
Glycerophosp holip id
N ame and Formula
ethan olamine
HOCH2 CH2 NH2
cephalin
ch oline
lecithin
serine
HOCH2 CHCOO
+
NH3
cephalin
+
HOCH2 CH2 N(CH3 ) 3
inositol
HO
HO
OH
ph os phatidylinositol
OH
OH
OH
I - lecithin
If the other alcohol is choline, a quaternary ammonium
compound, the glycerophospholipids are called phosphatidylcholines (common name lecithin):
 Lecithin is a major component of egg yolk. Because it includes
both polar and nonpolar portions within one molecule, it is an
excellent emulsifier and is used in mayonnaise.
 when a phospholipid such as lecithin is part of a lipid bilayer,
the hydrophobic tail points toward the middle of the bilayer,
and
 the hydrophilic heads line both the inner and outer surfaces of
the membranes
linolenic acid
O
choline
O
+
O P OCH2 CH2 N(CH3 ) 3
OCH2
O CH
O CH2
O
palmitic acid
glycerol
II - Cephalins, which are similar to the lecithins in
every way except that, instead of choline they
contain other alcohols,. such as ethanolamine or
serine
III - glycerophospholipids (phosphatidyli- nositols (PI)).
In PI, the alcohol inositol is bonded to the rest of
the molecule by a phosphate ester bond.
• Such compounds are integral structural parts of
the biological membranes, and, in their higher
phosphorylated
form,
such
as
phosphatidylinositol 4,5-bisphosphates (PIP2),
serve as signaling molecules in chemical
communication
What Are Sphingolipids?
Myelin, the coating of nerve axons, contains a
different kind of complex lipid
In sphingolipids, the alcohol portion is
sphingosine
The combination of a fatty acid and sphingosine
is called the ceramide portion of the molecule
The ceramide part of complex lipids may contain
different fatty acids. Stearic acid, for example,
occurs mainly in sphingomyelin.
( CH2 ) 12 CH3
( CH2 ) 12 CH3
HO
HO
NH2
OH
Sphingosine
O
NHCR
OH
A ceramide
(an N-acylsphingosine)
( CH2 ) 12 CH3
HO
O
NHCR
O+
OPOCH 2 CH 2 N( CH3 ) 3
O
A sphingomyelin
• A long-chain fatty acid is connected to the NH2 group by an amide bond, and the -OH
group at the end of the chain is esterified by
phosphorylcholine:
Sphingomyelins are the most important lipids in
the myelin sheaths of nerve cells and are
associated with diseases such as multiple
sclerosis.
Sphingolipids are not randomly distributed in
membranes.
Johann
Thudichum,
who
discovered
sphingolipids in 1874, Sphingolipids appeared
to Thudichum as part of a dangerous riddle of
the brain.
What are Glycolipids?
Glycolipids are complex lipids that contain
carbohydrates and ceramides.
the cerebrosides, consists of ceramide mono - or
oligosaccharides.
tthe gangliosides, contain a more complex
carobohydrate structure.
A glucose or galactose carbohydrate unit forms a
beta-glycosidic bond with the ceramide portion
of the molecule.
The cerebrosides occur primarily in the brain
(accounting for 7% of the brain's dry weight) and
at nerve synapses.
(CH2 ) 1 2 CH3
a ceramide
a unit of
-D-glucopyranose
HO
O
NHCR
H OH
HO
HO
HO
O
H
H
OH
H
a-glycosidic bond
What Are Steroids?
They are compounds containing the following
ring system:
In this structure, three cyclohexane rings
(A, B, and C); a fused cyclopentane ring (D).
 Steroids are thus completely different in
structure from the lipids already discussed.
 Note that they are not necessarily esters,
although some of them are.
A. Cholesterol
The most abundant steroid in the human body, and
the most important
Cholesterol serves as:
 a plasma membrane component in all animal
cells ( in red blood cells).
Its second important function is to serve as a raw
material for the synthesis of other steroids, such
as the sex and adrenocorticoid hormones and
bile salts.
HO
cholesterol
Cholesterol exists both in the free form
(Gallstones) and esterified with fatty acids.
When the cholesterol level exceeds
150 mg/l00 mL, cholesterol synthesis in the liver
is reduced to half the normal rate of
production.
B. Lipoproteins: Carriers of Cholesterol
• Cholesterol, along with fat, is 'transported by lipoproteins.
Most lipoproteins contain a core of hydrophobic lipid
molecules surrounded by a shell of hydrophilic molecules
such as proteins and phospholipids
There are four kinds of lipoproteins:
 High-density lipoprotein (HDL) ("good cholesterol"), which
consists of about 33% protein and about 30% cholesterol
 Low-density lipoprotein (LDL) ("bad cholesterol"), which
contains only 25% protein but 50% cholesterol
 Very-Iow-density lipoprotein (VLDL), which mostly carries
triglycerides (fats) synthesized by the liver
 Chylomicrons, which carry dietary lipids synthesized in the
intestines
Composition (% dry weight)
Cholesterol PhosphoTriProteins and esters lipids glycerides
Lipoprotein
High-density
lipoprotein (HDL)
33
30
29
8
Low-density
25
lipoprotein (LDL)
Very-low density
10
lipoprotein (VLDL)
50
21
4
22
18
50
8
7
84
Chylomicrons
1-2
C.Transport of Cholesterol in LDL
1.
2.
3.
4.
Ttransport of cholesterol from the liver starts out as a large
VLDL
(55 nanometers in diameter).
The core of VLDL contains triglycerides cholesteryl esters,
(cholesteryl linoleate). It is surrounded by a polar coat of
phospholipids and proteins.
The VLDL is carried in the serum. When the capillaries reach
muscle or fat tissues, the triglycerides and all proteins except
apoB-l00 are removed from the VLDL.
At this point, the diameter of the lipoprotein shrinks to 22
nanometers and its core contains only cholesteryl esters.
Because of the removal of fat, its density increases and it
becomes LDL.
5. The LDL carries cholesterol to the cells, where specific
LDL-receptor molecules line the cell surface in certain
concentrated areas called coated pits.
6. The apoB-l00 protein on the surface of the LDL binds
specifically to the LDL-receptor molecules in the
coated pits.
7. After such binding, the LDL is taken inside the cell
(endocytosis), where enzymes break down the
lipoprotein.
8. In the process, they liberate free cholesterol from
cholesteryl esters.
In this manner, the cell can, for example, use cholesterol
as a component of a membrane.
• Michael Brown and Joseph Goldstein of the
University of Texas shared the Nobel Prize in
medicine in 1986 for the discovery of the
LDL-receptor-mediated pathway.
If the LDL receptors are not sufficient in
number, cholesterol accumulates in the blood;
this accumulation can happen even with low
intake of dietary cholesterol.
Both genetics and diet play a role in determining
cholesterol levels in the blood.
D. Transport of Cholesterol in HDL
While in the serum, the free
cholesterols in HDL are converted to
cholesteryl esters.
These esterified cholesterols are
delivered to the liver for synthesis of
bile acids and steroid hormones.
What Are Some of the Physiological Roles
of Steroid Hormones?
Cholesterol is the starting material for the synthesis
of steroid hormones.
In this process, the aliphatic side chain on the
D ring is shortened by -the removal of a sixcarbon unit, and the secondary alcohol group
on carbon 3 is oxidized to a ketone.
The resulting molecule, progesterone, serves as
the starting compound for both the sex
hormones and the adrenocorticoid hormones.
A. Adrenocorticoid Hormones
The adrenocorticoid hormones are products of
the adrenal glands.
The term adrenal means "adjacent to the renal"
(which refers to the kidney).
We classify these hormones into two groups according to
function:
1-Mineralocorticoids
regulate the concentrations of ions (mainly Na+ and K+),
 Aldosterone is one of the most important
mineralocorticoids.
Increased secretion of aldosterone enhances the
reabsorption of N a + and Cl- ions in the kidney tubules
and
Increases the loss of K+.
Because
Na + concentration controls water
retention in the tissues, aldosterone controls
tissue swelling
.
2- glucocorticoids
control carbohydrate metabolism.
 Cortisol is the major glucocorticoid.
Its function is to increase the glucose and glycogen concentrations in
the body.
This accumulation occurs at the expense of other nutrients. Fatty acids
and amino acids from body proteins are transported to the liver,
which, under the influence of cortisol, manufactures glucose and
glycogen from these sources.
Cortisol and its ketone derivative, cortisone, have remarkable
antiinflammatory effects.
These or similar synthetic derivatives, such as prednisolone,
are used to treat inflammatory diseases of many organs,
rheumatoid arthritis, and bronchial asthma.
B. Sex Hormones
The most important male sex hormone is
testosterone.
This hormone, which promotes the normal growth
of the male genital organs, is synthesized in the
testes from cholesterol.
During puberty, increased testosterone production
leads to such secondary male sexual
characteristics as deep voice and facial and body
hair.
Female sex hormones,
the most important of which is
estradiol,
are synthesized from the corresponding male
hormone (testosterone) by aromatization of the
A ring:
CH3
H3 C C= O
H3 C
O
several
steps
H3 C OH
HO
Progesterone
Estradiol
H3 C OH
H3 C
H3 C
O
H3 C
HO
Testosterone
Androsterone
O
Estradiol, together with its precursor progesterone,
regulates the cyclic changes occurring in the uterus and ovaries
known as the
menstrual cycle.
 As the cycle begins, the level of estradiol in the body rises,
which in turn causes the lining of the uterus to thicken.
Another hormone, called luteinizing hormone (LH), then
triggers ovulation.
 If the ovum is fertilized, increased progesterone levels will
inhibit any further ovulation.
Both estradiol and progesterone promote further preparation of
the uterine lining to receive the fertilized ovum.
 If no fertilization takes place, progesterone production stops
altogether, and estradiol production decreases.
This halt decreases the thickening of the uterine lining, which is
sloughed off with accompanying bleeding during menstruation
Because progesterone is essential for the
implantation of the fertilized ovum,
 Progesterone interacts with a receptor
in the nucleus of cells.
 The receptor changes its shape when
progesterone binds to it its action leads to
termination of pregnancy
What Are Bile Salts?
Bile salts are oxidation products of cholesterol.
First the cholesterol is oxidized to the
trihydroxy derivative,
and the end of the aliphatic chain- is oxidized to
the carboxylic acid.
The latter, in turn, forms an amide bond with an
amino acid, either glycine or taurine:
H3 C
HO
CH3
H3 C
HO
CH3
NH
COO-
H3 C
HO
O
OH
Glycocholate
(from glycine )
H3 C
HO
OH
Taurocholate
(from taurine )
O
NH
SO 3 2 -
Taurine has developed a certain amount of
commercial importance in recent years as an
ingredient in sports drinks.
The drink marketed under the trade name Red
Bull contains various sugars , caffeine, and B
vitamins in addition to taurine,
Bile salts are powerful detergents.
One end of the molecule is strongly hydrophilic
because of the negative charge,
and the rest of the molecule is largely
hydrophobic.
As a consequence, bile salts can disperse dietary
lipids in the small intestine into fine emulsions,
thereby facilitating digestion.
The dispersion of dietary lipids by bile salts is
similar to the action of soap on dirt.
Because they are eliminated in the feces,
bile salts remove excess cholesterol in two
ways:
(1) They are themselves breakdown products of
cholesterol (so cholesterol is eliminated via
bile salts), and
(2) they solubilize deposited cholesterol in the
form of bile salt-cholesterol particles.