Biochemistry of Lipids
Objectives:
- Recognize the features and Functions of different classes of “Lipids”
- Understand the nomenclature and the physical properties of fatty acids and the relation
of these properties to the saturation state of the fatty acids.
- Recognize the structure and the function of different classes polar lipids.
- Recognize the structure most popular examples for each class of lipids.
- Understand the role lipids as pigments, signals and cofactors, knowing different
examples
•Classification
1. Storage lipids.
2. Structural lipids in membranes.
3. Lipids as signals, cofactors and pigments.
Storage Lipids
• Fatty acids are hydrocarbon derivatives.
-C4 to C36.
-Saturation.
-Nomenclature.
-Physical properties.
• Triacylglycerols.
-Simple vs. complex triglycerides.
-Functions: provide stored energy and insulation.
• Waxes.
-Functions: serve as energy stores and water repellents
Structural Lipids
• Types of membrane lipids:
1. Glycerophospholipids:
-Phosphatidic acid.
2. Sphingolipids:
-Sphingosine.
3. Sterols:
-Steroid nucleus.
-Functions.
Lipids as signals, cofactors and pigments
• Phosphatidylinositols act as intracellular signals.
Eicosanoids carry messages to nearby cells.
-Prostaglandins.
-Thromboxanes.
-Leukotrienes.
• Steroid hormones carry messages between tissues.
• Vitamins A.
• Vitamins D.
• Vitamins E.
• Vitamins K.
References
Chap. 11 of Lehninger
Lipids
Defined on the basis of solubility.
Lipids: heterogeneous group of water insoluble (hydrophobic) organic
molecules, they are chemically diverse compound but have one feature:
water insoluble
Many distinct chemical species in a “lipid fraction”
Functions
-The biological functions of lipids are divers as their chemistry
Lipids perform three biological functions:
1. Lipids in form of a bilayer are essential components of biological
membranes.
2. Lipids containing hydrocarbon side chains serve as energy stores.
3. Many intra-and intercellular signaling events involve lipid molecules.
Lipid Classification
1. Storage lipids
Triglycerides, Waxes and Fatty acids.
Fats and oils are stored forms of energy and are derivatives of fatty acids.
2. Structural lipids in membranes
Glycerophospholipids, Sphingolipids, Sterols.
are major structural elements in biological membranes
3. Lipids as signals, cofactors and pigments.
These lipids presents in small quantities but play crucial roles
-Phosphatidylinositols,
Eicosanoids
- Prostaglandins.
- Thromboxanes.
- Leukotrienes.
- Steroid hormones carry messages between tissues.
- Vitamins A and D are hormone precursors.
- Vitamins E and K are oxidation-reduction cofactors.
Storage Lipids
Fats and oils are derivatives of Fatty acids.
Fatty acids (F.A) are carboxylic acids with long hydrocarbon chain ranging from 4-36
carbon atom 16- and 18-C long are most abundant.
-Even number of carbons, 16, 18… the odd are also present but rare.
-the hydrocarbon chain can be fully saturated (without double bonds), or with one, two or
three double bonds (cis-configuration only)
- usually they are unbranched, some cases have methyl, hydroxyl, or three-carbon ring as
branch
Nomenclature
Numbered from carboxyl end
specify the chain length and the number of
double bonds separated by colon
Palmitic acid is saturated F. A with 16 C
atoms Î 16:0
Stearic acid Î 18:0
Linoleic acid Î 18:2(Δ
9,12)
Arachodonic acids Î20:4 (Δ
5,8,11,14)
The position of double bond should be specified superscript
numbers following the Δ
(delta)
Oleic acid Î 18:1(Δ 9)
Linoleic acid Î 18:2(Δ
9,12)
Linolenic acid Î 18:3(Δ
9,12,15)
the location of double bonds is 9=10; 12=13; 15=16
Arachodonic acids Î20:4 (Δ
5,8,11,14)
-the polyunsaturated F. A are never conjugated, the double bond is
separated by methyl group
1
9
Longer the fatty acid chain -Higher the melting temperature
( i.e. more solid at room temp)
More double bonds -lower the melting temperature
( i.e. more liquid at room temperature )
Omega Fatty acids
-Essential F.A
Linoleic (18:2Δ9,12)
ω6
Linolenic (18:3Δ9,12,15)
ω3
Arachidonic (20:4Δ5,8,11,14)
ω6
Physical properties of fatty acids
Physical properties of F. A and the compounds containing them are largely
determined by the length and degree of unsaturation of the hydrocarbon chain
Solubility:The non-polar hydrocarbon chain account for the poor solubility of F.
A in water
Lauric acid 12:0 Mr 200 Î sol. In water 0.063 mg/g
Glucose M.wt 180 Î water sol. Is 1.1mg/g
*The carboxyl group is polar and this accounts for the slight solubility of short
chain fatty acid in water
*The longer the fatty acid acyl and fewer the double bonds, the lower is the
solubility in water
Melting points
melting points are strongly influenced by the length and degree of unsaturation
-at R.T the saturated F. A with length chain 12-24 have waxy consistency while
the unsaturated F. A are liquid
fully saturated molecule Î
free rotation around each C-C
This gives the hydrocarbon
chain great freedom and
flexibility
Î adopt the most stable
conformation which is the
fully extended form in which
the steric hindrance of
neighboring atoms is minimized
Saturated chains pack
tightly and form more
rigid, organized
aggregates
The molecules can pack together
tightly in nearly crystalline arrays.
So the Vander Waal interaction
and the hydrophobic interaction
are maximized
High thermal energy required to
disorder (melt) these highly
ordered F.A molecules Î higher
melting points
In the unsaturated F. A
the cis configuration
double bond forces a kink
(bend) in the hydrocarbon
chain
Unsaturated chains bend
and pack in a less ordered
way, with greater potential
for motion
F.A with one or more kinks cannot
pack together as tightly as fully
saturated F.A and their
interactions are weaker
So the unsaturated F.As take less
thermal energy to disorder these
poorly ordered arrays of
unsaturated F.As Î they have
lower melting points
Triacylglycerols or Triglycerides
Fatty acid triesters of glycerol
Most contain two or three different types
of fatty acid residues
triglycerides are non-polar and
hydrophobic molecules(the polar groups
of both glycerol and F. A are are linked
in ester linkage Î non-polar molecule )
Simple triacylglycerols: containing
the same kind of F.A in all three positions
of glycerol
Simple triacylglycerols of
18:0 = tristearin
16:0 tripalmitin
18:1 triolein
Mixed triacylglycerols: different fatty
acids esterified with glycerol
Fats and oils
* Plant oils are usually richer in unsaturated fatty acids residues than animal fats
* Fats and oils are complex mixtures of mixed triacylglycerols and simple
triacylglycerols
*Triacylglycerols can be found in most eukaryotic cell as oily droplets in the aqueous
cytosol serving as metabolic fuel *In vertebrates specialized cells called Adipocytes
(fat cell) store amounts of triglycerides as fat droplets that fill the cell.
Triglycerides also stored as oil in the seeds of many types of plants .
*Adipocytes contain lipases catalysis the hydrolysis of stored triglycerides releasing
F.A for export to sites where they can be used as fuel.
*Two advantages for using the triglycerides as stored fuel rather than
polysaccharides as glycogen and starch:
1- the carbon atoms of F.A are more reduced than that of carbohydrates Î
oxidation of triglycerides yields more than twice as much energy (gm/gm) as the
oxidation of CHO
2- triglycerides are hydrophobic Î unhydrated, the organism that carries fat as
fuel does not have to carry the extra weight of water of hydration that is
associated with stored polysaccharides (2gm water/1gm polysaccharides
Fats function as energy reservoirs in animals
The fat content of normal humans allows them to survive starvation for 2 or 3
months
While human store of glycogen can supply only for one day but carbohydrates
are quick sources for metabolic energy because of water solubility
Fat stores: skin, abdominal cavity and mammary gland Triacylglycerols
Triacylglycerols function to insulate: protect the body from the outer
environments
Vegetable oils: are composed of Triacylglycerols with unsaturated fatty acids Æ
liquid at room tem.
Vegetable oils can be into solid by catalytic hydrogenation which reduce the
double bonds to single bonds.
* Exposure of the lipid rich food to oxygen for long time Æ may spoil and the
lipid is said to be Rancid. Rancidity results from the cleavage of double bond in
unsaturated F. A that produce aldehyde and carboxylic acid with low M.wt Æ
bad smell
Waxes serve as energy store and water repellents
Biological waxes are esters of long chain (C14-C36) saturated and
unsaturated fatty acid with long chain alcohol (C16-C30) melting points
about 60-100 ºC
Function of Biological waxes
-Skin glands of some vertebrates secret waxes to protect hair and skin to
keep it pliable, lubricated and water proof
Leaves of many tropical plants are coated by waxes to prevent excessive
evaporation of water and protect against parasites
Waxes can be used in pharmaceutical industries in lotions, ointments and
polishes
Polar vs. Nonpolarlipids
•Non-Polar Lipids –Energy storage
•Polar lipids are the basis of Bilayers
Biological membranes
feature: double layer of lipid
act as barrier to the passage
of polar molecules and ions.
Amphipathic: one end of the
molecule is hydrophobic and
the other is hydrophilic
The hydrophobic interactions
between molecules and the
hydrophilic interactions with
water direct their packing
into sheets called membrane
bilayer
Glycerophospholipids
Glycerophospholipids are the major lipid component of biological membranes
-amphiphilic molecules with non-polaraliphatic tails and polar phosphoryl-X
heads
Phosphoglycerides: two F. A are attached in ester linkage to the first and
second carbons of glycerol and a highly charged group is attached through a
phosphodiester linkage to the third carbon
Glycerophospholipids
“Phospholipids”
*some animal tissues are rich in ether
lipids: one of the acyl group is
attached to glycerol in ether rather
than ester linkage. The ether-linked
chain can be maybe saturated alkyl
ether lipid or may unsaturated alkeneether linked chain
Platelet activating
factor: released from
leukocyte (basophiles)
and stimulate platelet
aggregation and the
release of serotonin
Plasmalogen: ether linked alkene found in
heart tissue, 50% of the phosphlipid in the
heart is Plasmalogen
Sphingolipids
Sphingolipids are major membrane components, with polar head and non-polar tail
• They are derivatives of the C18 amino alcohol sphingosine
• The double bond in sphingosine is trans
• C1, C2, C3 of sphingosine molecule are structurally similar to the three carbons of
glycerol in phospholipids
• N-acyl fatty acid derivatives of sphingosine are known as ceramides
• Ceramides are the parent compounds of the more abundant sphingolipids.
General structure of Sphingolipids, if X is H, the compound is Ceramide
Sphingomyelins: contain phosphocholine or phosphoethanolamine as their
polar group and so can be classified as phospholipids.
Sphingomyelins resemble phosphotidylcholines in their general properties
and three-dimensional structure and in having no net charge on their head
groups
The myelin sheath that surrounds and insulates nerve cells is rich in
Sphingomyelins
Glycosphingolipids (Glycolipids): occur largely in the outer face of plasma membrane, have one
or more sugars connected directly to the –OH at C1 of the ceramide moiety and can be
classified
A- Neutral Glycolipids (uncharged)Î no net charge at pH=7
1- Cerebroside: single sugar linked to ceramide usually Glucose or Galactose
2- Globoside: Di, tri or tetrasaccharide linked to ceramide as Glu, Gal, N-acetly galactosamine
B- Ganglioside: the most complex glycolipid, have oligosaccharide as their polar head groups
and one or more residues of Sialic acid
Ganglioside are primarily components of membranes on cell surfaces and constitute 6% of
brain lipids
Sphingolipids: act as a site of biological recognition, act as receptors for hormones and
glycoproteins
3-Sterols
Structural lipids present in the
membranes of some eukaryotic cells.
Characterized by the steroid nucleus
consisting of four fused rings three
rings with 6 C atoms and one ring with 5
C atoms, the steroid nucleus is relatively
rigid and planar
Cholesterol is the major sterol in animal
tissues and it is amphipathic with a polar
head (the –OH group), and the non-polar
body is the steroid nucleus
Similar sterols are present in
eukaryotes: StigmasterolÎ plants
ErgosterolÎ fungi
Functions
- Membrane constituents
- Precursors of different product with vital biological activities (steroidal
hormones that regulate the gene expression)
- Bile acids are derivatives of cholesterol that act as emulsifying agent in the
intestine
Lipids as Signals, cofactors and pigments
Group of lipids present in small amounts play various essential function
- Have active roles in metabolic processes as metabolite and messenger
- Potent signals and hormones carried in the blood from one tissue to others
- Intracellular messengers generated to response to outer signal
- Can function as cofactors
- Pigments
- Fat soluble vitamins
Phosphotidyl inositol: act as intracellular signals:
Intracellular messengers are released from the Phosphotidyl inositol in response
to extra cellular signals interacting with receptors on the outer surface of the
membrane
* Signals act through a series of steps
IP3
Eicosanoids: are paracrine hormones; substances that act only on site cells near the point of
synthesis instead of being transported in the blood to act on other cells or tissues.
Eicosanoids are derived from membrane lipids and mainly from Arachodonic acid
[20:4(Δ5,8,11,14 ]
1- Prostaglandins
•C20 compounds
• Five carbon ring
• affect a wide range of cellular and tissue function
•Act at low concentration and are involved in the production of pain and fever, regulation of
blood pressure, blood coagulation and reproduction
•Produced and used locally
• Regulate the synthesis of the intracellular messenger (cAMP) which mediate the action of
different hormones.
-Stimulate the contraction of smooth muscle in uterus
-Affect the blood flow
-Elevate the body temperature and mediate the inflammation and pain
2- Thromboxanes:
Six-memebred ring containing an ether, produced by the platelets (thrombocytes) and play
role in formation of the blood clots
3- Leukotriens: contain conjugated double bonds, found in the leukocytes, powerful biological
signals, induce contraction of muscles lining the airways of the lung. Over production cause
asthmatic attack
Aspirin and NSAIDs
•Aspirin inhibits the synthesis of prostaglandins from arachidonicacid by chemically
modifying a serine residue of the enzyme PGH2 synthase (Cyclo oxygenase enzyme)
preventing arachidonicacid from reaching the enzyme active site
•Non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen and acetaminophen)
non covalently bind to PGH2 synthase, also preventing arachidonicacid from
reaching the enzyme active site
•Leukotrienes have been implicated in various inflammatory and hypersensitivity
disorders (such as asthma). They are synthesized from arachidonateby an aspirininsensitive pathway
Steroidal anti-inflammatory drug
Prednisone and prednisolone inhibit the phospholipase A2 that release the
Arachodinic acid from the phospholipids in the membrane Î the synthesis of all
eicosanoid will be inhibited
Steroidal Hormones
Steroids: oxidized form of the
sterol, with the steroid nucleus
but lack the alkyl chain
-More polar than cholesterol
-Move through the blood on
proteins carriers from site of
production to target tissue.
Then bind to their receptors
Î enter the nucleus Î affect
the gene expression and
metabolism
-male and female sex hormones
(Testosterone and estradiaol)
-adrenal cortex hormone:
cortisol and aldesterone
-Prednisone and prednisolone
are synthetic steroids
Lipid Soluble Vitamins
Vitamins: Compounds that are essential to the health of human and other animals
and most of the vitamins cannot be synthesized by endogenously
Two classes of Vitamins
a.
Fat soluble vitamins
b.
Water soluble vitamin, Vit B and Vit C
Vitamin D
A group of structurally related compounds that play a role in the regulation of
calcium and phosphorus metabolism
-the most abundant form in the circulatory system is vitamin D3
(Cholecalciferol) which is formed in the skin from 7-dehydrocholesterol
-Vit D3 is converted into the active form in two steps the first at the liver and
the second at the kidney
-The active form of vit D3 (1,25-dihydroxycholecalciferol) regulates the Ca
uptake in the intestine and Ca levels in the kidney
-Deficiency of Vit D3 Î defective bone formation and Rickets disease
Vitamin D activation
Vitamin A (Retinol)
•Vit A with its precursors and its derivatives function as hormones and as the
visual pigments in the eye
• β-carotene: yellow pigments in the carrot
Retinoic acid : is a derivative of Vit A and can regulate gene expression in the
development of epithelial tissue (skin)
Vitamin E
•Vitamin E is a group of compounds of similar structure; the most active is
α-tocopherol
- Associates with cell membranes, lipids, lipoproteins in the blood
- An antioxidant; traps HOO• and ROO• radicals formed as a result of
oxidation by O2 of unsaturated hydrocarbon chains in membrane phospholipids
Î protect the unsaturated F.A from oxidation and prevent oxidative damage
to membrane lipid
-Deficiency of Vit E : Rough skin, muscular weakness and sterility
Vitamin K
•Blood clot factor: undergo a cycle of oxidation reduction during the
formation of the active prothrombine
•Different forms, most common n=8
•Functions in blood clotting
Vit K1 (Phylloquinone)
The End