LIPIDS

Overview
1. The role of Lipids
2. Main components and Properties of Lipids
3. Classification of lipids
- Triglycerides
- Phospholipids
- Sterols
- Ecosanoids
- Isoprenoids
5. Lipid Digestion
6. Transport of lipids
7. Lipoprotein Metabolism
 Lipids Functions
1. Provide Energy (9 kcal/g).
.Protects vital organs against shock .2
.Insulates body against temperature extremes .3
.Carrier of fat soluble vitamins A,D,E, and K .4
.Give flavor to foods .5
Important components of membranes .6
Helps body use carbohydrates and protein efficiently .7
 Nomenclature
1. Based on hydrocarbon molecule with the number and
arrangement of carbon atoms

saturated = anoic; octanoic acid (octa =8)

 unsaturated = enoic; octadecenoic acid (octa = 8 and deca = 10,

thus 18)
• Palmitic (hexadecanoic);16:0
• Palmitoleic acid: 9-hexadecenoic acid
• Stearic acid: Octadecanoic acid): 18:0
• Oleic Acid (Δ9,-octadecenoic);18:1; Δ 9
• Arachdonic acid (Δ 5,8,11,14-eicosatetraenoic acid)

Acyl & Alkyl Group: Acyl group is a functional group formed by the double-bonded
Carbon and Oxygen. Alkyl groups consist of only Carbon and Hydrogen atom.
Nomenclature & Carbon Numbering
Delta (Δ) System:
• Carbon 1 is assigned to the carbon of the functional group
• Chain is numbered to assign locator numbers to the first carbon in each
carbon-carbon double bond present in the molecule.

Omega (ω) system

• Carbon 1 is assigned to the carbon farthest from the functional group.
• Omega system only indicates the location of the first carbon of the first carbon-
carbon double bond.
 Nomenclature & Carbon Numbering
• The functional group C=O is called a “carbonyl” and the oxygen is called “the
carbonyl oxygen”.
• Carbon adjacent to a carbonyl is given Greek alphabet and called an “α (alpha)
carbon”, two carbons away is called a “β carbon”, and so on…..
Numbering of carbon chains in lipid
Classification of lipids
Eicosanoids
Lipid-based signaling molecules that play a unique role in innate immune responses
that allows the innate immune cells to respond rapidly to bacterial invaders.. E.g
prostaglandins (PGs) and leukotrienes (LTs)

Waxes
Type of long chain nonpolar lipid. Natural waxes are typically esters of fatty acids and
long chain alcohols. Waxes are synthesized by many animals and plants.

Ceramides
• They make up 30% to 40% of the outer skin layer, or epidermis.
• Important for retaining skin's moisture and preventing the entry of germs into the
body.

Polyprenols
Natural long-chain isoprenoid alcohols of the general formula H-n-OH where n is the
number of isoprene units. Important membrane structure.

Plasmalogens
Glycerphospholipids which modulate membrane trafficking, cell signaling, transporter
functions, oxidative status, and storage of PUFA eventually affecting cognitive functions
and behavior.
 Classification
1. free fatty acids & triglyceride:
• Fuel and energy metabolism. e.g. TG
• Metabolic regulators. e.g. TG and eicosanoids

2. complex lipids:
• Membrane structure
• cholesteryl ester is the major form in for cholesterol transport or
storage
3. Length of Fatty Acids
 4. Based on bonds and saturation

Saturated Fatty acids

No double bonds:
1. lauric acid (laurate) (12:0)
2. myristic acid (myristate) (14:0)
3. palmitic acid (palmitate) (16:0)
4. stearic acid (stearate) (18:0)
Monounsaturated Fatty Acids
One double bond
1. Oleic acid (oleate) (18:1cis)
2. Elaidic acid (elaidate) (18:1trans)

Polyunsaturated Fatty Acids

Two or more double bonds
1. Linoleic acid (linoleate) (18:2; 9,12) ω6
2. Linolenic acid (linolenate) (18:3; 9,12,15) ω3
3. Arachidonic acid (arachidonate) (20:4; 5,8,11,14) ω6
Properties chemical reactions of Lipids

Saponification

Solubility

Isomeration

Melting temperature

Halogenation

Oxidation
 Saponification number, Acid value & Iodine number

Alkali hydrolysis of fatty acids

R-COOH + NaOH RCOONa+H2O
Saponification value: The number of milligrams of
NaOH/KOH needed to neutralize the fatty acids obtained by
complete hydrolysis of 1gram of fatty acids.

Acid Value: Number of mgs of KOH/NaOH required to neutralize

.the Free Fatty Acids in 1 g of fat

Iodine Number: It is defined as the number of grams of iodine

absorbed by 100 g of fat.

All reactions indicates degree of fatty acid unsaturation.

 Isomerization
1. Cis: Both H-atoms are on the same side of the double bond (nearly
all naturally occurring fatty acids)

2. Trans: two H-atoms are on opposite sides of the double bond.

• Trans fats are present in

certain foods
• Most arise due to partial
hydrogenation (saturation) of
polyunsaturated fatty acids of
natural oils (margarine)
 Hydrogenation
• Hydrogenation: process of replacing some double bonds of
polyunsaturated fats with hydrogen atoms. The process by which
vegetable oil becomes margarine.

• When vegetable oils are hydrogenated, some double bonds

undergo a change in configuration and are concerted to “Trans
Fatty Acids”.

The “Cis” configuration is typical of the fatty acid in natural •

.foods

The “Trans” fatty acids (formed during hydrogenation) may raise LDL •
and lower HDL level.
Melting Points and Solubility in Water

Melting Point
Temperature

Solubility in H O
2

Chain Length
 Lipid peroxidation
 Peroxidation (auto-oxidation) of lipids is responsible for deterioration of foods and
also damage of tissues which causes cancer, inflammatory disease, atherosclerosis,
etc.

 The reaction is initiated by an existing free radical (X .), by light or by metal.

 The deterioration effects cause by free radicals (ROO ., RO. , OH. ) produced during
peroxide formation from fatty acids (unsaturated)
Ester Formation
• Condensation reaction between an alcohol and a carboxylic acid.
• Two molecules join and produce a larger molecule whilst eliminating a small molecule
as water.
• Esters have characteristic smells and are insoluble in water.

RCOOH + R−OH RCOOR

 Alcohol

Glycerol

Phosphoglycerol

Monohydric alcohol

Sterol

Amine Alcohol (Sphingosine)

 Structure of glycerols

C3H8O3
Glycerol is the basis of Triglyceride Phosphoglycerol is basis of Phospholipids
 Triglycerides
1. In Triacylglycerol (TG) all 3 –OH of glycerol are esterified by FAs.
2. Monoacylglygerol and diacylglycerol have, respectively, 1 and 2 FAs
3. Naturally occurring glycerol is L-glycerol.
4. TG are the storage form of FA; most dietary fats are triglycerides
5. Physiologically, TG are digested in the small intestine by the enzyme
pancreatic lipase Monoacylglycerols are absorbed through the intestinal cells,
re-converted to TG and assembled into lipoproteins

Source of TG
1. 90 % of dietary fat intake and 95% of fat stored in tissues
2. Plant sources – high in polyunsaturated fatty acids (oils)
3. Animal sources – high in saturated fatty acids (fats)
 Phospholipids
Glycerophospholipid

Phosphatidate
Phosphatidylcholin
Phosphatidylglycerol
Phosphatidyl Serine
Phosphatidyl ethanolamine
Phosphatidylinositole 4,5
bisphosphatae
Cardiolipin
Lysolicithin
Plasmalogen
 Phospholipids
1. Phospholipids (lecithin) are composed of Glycerol backbone; 2 fatty
acids; Phosphate.
2. Are partially soluble in water
3. Are manufactured in our bodies so they are not required in our diet
4. At least one fatty acid and one phosphorus compound attached to
glycerol

Functions of phospholipids
1. Are amphipathic so can act as emulsifiers
2. Important component of cell membranes
3. Present on the outer surface of lipoproteins, allowing them to
float freely in the blood
4. Especially important for insulation of nerves (in the myelin
sheath as Sphingomyelin)
 Structure of glycerophospholipids
They consist of:
• Two nonpolar fatty acid tails joined by a glycerol backbone at C1 & C2
• A polar phosphate head group linked with different molecules (serine or choline), to
generate diverse kinds of phospholipids.
• Phosphate group is hydrophilic attached to C3

‘R’ Maybe:
• Methyl (-CH3),
• Ethyl (-CH2CH3) X
• Propyl-(CH2CH2CH3),
• Butyl (-CH2CH2CH2CH3)
Classification of glycerophospholipids
 Phosphatidylcholine

Functions:
• Proper metabolism of fats;
• Facilitates the movement of fats in and out of cells. In liver, it exports the fat
from the hepatocytes (Choline deficiency=Fat accumulation, fatty liver,
cirrhosis)
• choline acts in the human body as a methyl donor.
• Needed for cell membrane integrity by synthesizing phosphatidylcholine and
•
Sphingomyelin.
• Plays a crucial role in many brain processes, including memory.
• Increases the solubility of cholesterol and thereby decreases cholesterol‘s
• ability to induce atherosclerosis.
 Therapeutic Uses
• Liver Disorders
• Detoxification
• Hypercholesterolemia and Atherosclerosis
• Manic depressive disorder
• Alzheimer’s Disease
 Phosphatidylethanolamine
• The second most abundant phospholipid in animal and plant
lipids and main lipid component of microbial membranes.
• It can amount to 20% of liver phospholipids and as much as 45%
of those of brain.
• In contrast to phosphatidylcholine, it is concentrated with
phosphatidylserine in the inner leaflet of the plasma
membrane.
 Phosphatidylserine
• It exists in your brain cell membranes, or the part of your cell
that protects the inside of the cell from the outside environment.
• It plays a key role in cell cycle signaling, specifically in relation
to apoptosis. It is a key pathway for viruses to enter cells via
apoptotic mimicry by acquiring host phosphatidylserine.
• Phosphatidylserine is used for Alzheimer disease and normal
age-related decline in memory and thinking skills
 Cardiolipin
• Cardiolipin (bisphosphatidyl glycerol) is an important component
of the inner mitochondrial membrane, where it constitutes about
20% of the total lipid
Phosphatidyl Glycerol + Phosphatidic Acid

Functions:
o Triggers apoptosis
o Serves as proton trap for oxidative phosphorylation
o Cholesterol translocation from outer to the inner membrane of mitochondrial
o Import protein into mitochondrial
 Phospholipase A2

Indican Cobra Eastern Diamondback Rettlesnake

1. The Poisonous Snakes contain Phospholipase A2 that breakdown

Lecithin and produces Lysolecithin
2. Lysolecithin acts a detergent and dissolves of membrane of red
blood cells.
Sphingolipids
Sphingophospholipid
Sphingomyelin
Sphingoglycolipids
Cerebrosides
Gangliosides
Sulfatide
 Sphingolipids
Sphingolipids
1. Sphingosine is a derivative of glycerol but it has –NH2 instead of -OH at C2 and
has a -OH as well as a long chain hydrocarbon on C3
2. The –NH2 forms an amide bond with a long chain FA to form a ceramide.
sphigomyelin is formed when a phosphodiester bridge links the C1 -OH of
ceramide to ethanolamine or choline
3. Sphingomyelin are found abundantly in the myelin sheath that surrounds the
nerve fibers

Glycolipids
1. Glycolipids are lipids that contain carbohydrates
2. Cerebrosides have a monosaccharide attached to the C1 -OH of ceramide
3. Gangliosides have an oligosaccharide attached to the C1 -OH of ceramide
4. Cerebrosides and gangliosides are found in the brain and nervous tissue
 CH=CH(CH 2)12CH 3 CH=CH(CH 2)12CH 3
HO CH O HO CH O

HC N C(CH 2) 22CH3 HC N C(CH 2) 22CH3

H H

H2 C H2 C
O X O H

Sphingosine Sphingosine +H= Ceramide

 Ganglioside
Ganglioside
It is a compound composed of a glycosphingolipid with one or more sialic acid
(n-acetylneuraminic acid, NANA). The 60+ known gangliosides differ mainly in
the position and number of NANA residues.
Location
On cell surfaces, with the 2 hydrocarbon chains of the ceramide moiety
embedded in the plasma membrane and the oligosaccharides on the
extracellular surface. They are found predominantly in the nervous system
where they constitute 6% of all phospholipids.
Function
Gangliosides, glycosphingolipids, and glycoproteins found on the surface of
oligosaccharide provide cells with distinguishing surface markers that can
serve in cellular recognition (signal transduction) and cell-to-cell
communication.
Waxes
 Sterol
• Sterols: Lipids containing multiple rings of carbon atoms.
– Are essential components of cell membranes and many hormones
– Are manufactured in our bodies and therefore are not essential
components of our diet

Sterols are basis of Cholesterol, Bile Acids, Steroid hormones and Vitamin D
 Steroids
1. Sterols 3. Bile acids
Cholesterol A) Primary bile acids
• Cholic acid
2. Steroid Hormones • Chenodeoxycholic acid
• Progesterone,
• Cortisol B) Secondary bile acids
• Aldosterone • Lithocholic acid
• Testosterone • Deoxycholic acid
• Estradiol
• Calcitriol

4. Vitamin D
 Cholesterol

1. Cholesterol is a steroid consisting of 4 hydrocarbon rings linked together

2. Component of cell membranes
3. Not an essential nutrient and present in all the tissues
4. It has OH group that provides polarity and hydrocarbon at other end which is
hydrophobic
5. The underlying cause of heart attacks and strokes due to plaque formation
6. Not readily catabolized for energy
7. Converted in liver to bile acids
8. Converted by gonads and adrenals into steroid hormones
 Progesterone
1. It is synthesized in the corpus luteum of the ovaries.
2. The hormone prepares the uterus for a possible
pregnancy.
3. The development of the mammary glands is also
stimulated by progesterone
 Estradiol
Estradiol is the most important of the estrogens.

Like progesterone, it is synthesized by the ovaries and, during pregnancy, by the

placenta as well.

Estradiol controls the menstrual cycle.

It promotes proliferation of the Uterine mucosa, and is also responsible for the
development of the female secondary sexual characteristics (breast, fat distribution)
 Cortisol
1. Cortisol, the most important glucocorticoids, is synthesized by the
adrenal cortex.
2. It is involved in regulating protein and carbohydrate metabolism by
promoting protein degradation and the conversion of amino acids into
glucose.
3. As a result, the blood glucose level rises.
4. Synthetic glucocorticoids (e. g., dexamethasone) are used in drugs due to
their anti-inflammatory and immunosuppressant effects.
 Testosterone
1. Testosterone is the most important of the male sexual steroids
(androgens).
2. It is synthesized in the Leydig intersitial cells of the testes, and
controls the development and functioning of the male gonads.
3. It also determines secondary sexual characteristics in men (muscles,
hair, etc.).
 Aldosterone
1. Aldosterone, a mineralocorticoid, is also synthesized in the
adrenal gland. In the kidneys.
2. it promotes Na+ reabsorption by inducing Na+/K+ ATPase and
Na+ channels.
3. At the same time, it leads to increased K+ excretion. In this way,
aldosterone indirectly increases blood pressure.
 Calcitriol
1. Calcitriol is a derivative of vitamin D.
2. Calcitriol itself is synthesized in the kidneys.
3. Calcitriol promotes the resorption of calcium in the intestine and
increases the Ca2+ level in the blood.
 EICOSANOIDS

Eicosanoids act via membrane receptors in the immediate vicinity of their site
of synthesis, both on the synthesizing cell itself (autocrine action) and on
neighboring cells (paracrine action).

.Physiological functions of eicosanoids

Eicosanoid Functions
prostaglandins inflammation, fever production, prevent
platelet aggregation (prevent clotting);
induce labor
thromboxanes produced by platelets to promote their
aggregation (blood clotting)
leukotrienes allergic reactions
 Non Steroid Anti-inflammatory Drugs (NSAIDs )
1. Acetylsalicylic acid and related NSAIDs selectively inhibit the
cyclooxygenase activity of prostaglandin synthase and
consequently the synthesis of most eicosanoids.
2. Aspirin acetylates a serine hydroxyl group near the active site,
preventing arachidonate binding. The inhibition by aspirin is
irreversible.
3. Most other NSAIDs, such as indomethacin and ibuprofen,
inhibit cyclooxygenases by competing with arachidonate.

Selective COX inhibitors

Celecoxib .1
Rofecoxib .2
Because COX-2 is usually specific to inflamed tissue, there is much less gastric
irritation associated with COX-2 inhibitors, with a decreased risk of peptic
.ulceration
 Lipid transport in the circulation
Lipids are insoluble in plasma. In order to be transported they are combined with
specific proteins to form lipoproteins:
Proteins (apoproteins)

HO

O Non polar lipids in core

Cholesterol (TAG and cholesterol ester)
R

R
HO

HO

Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred
to another lipoprotein of a different class. Apoproteins have various functions including:
• Structural role
• Binding sites for receptors
Activators or co-enzymes for enzymes involved with lipid metabolism
 Classification of Lipoproteins
• Based on Electrophoresis
• Paper : chylo, beta, prebeta, alpha
• PAGE: chylo, prebeta, beta, alpha
Chylomicron remains at origin
in electrophoretic field

HDL, Alpha VLDL, IDL, Lpa in LDL, Beta

Prebeta
Density in centrifugation
1. chylomicrons
2. very low density lipoproteins (VLDL)
3. intermediate density lipoproteins (IDL)
4. low density lipoproteins (LDL)
5. high density lipoproteins (HDL)
 The five classes of lipoprotein
(all contain characteristic amounts TAG, cholesterol, cholesterol esters, phospholipids and apoproteins)

Diameter Major
Class Source and function
(nm) apoliproteins
Chylomicrons Intestine. Transport of dietary A, B48, C(I,II,III)
(CM) 500 TAG E
Liver. Transport of endogenously
B100, C(I,II,III) ,
Increasing density

43 synthesised TAG
VLDL E
Formed in circulation by partial
LDL 22 breakdown of IDL. Delivers B100
cholesterol to peripheral tissues
Liver. Removes “used” cholesterol
from tissues and takes it to liver.
HDL 8 Donates apolipoproteins to CM A, C(I,II,III), D, E
and VLDL
Methods to measure the constants of fats and oils
Acid Value.1
.Saponification Value .2
Iodine Value .3
Gas Chromatographic Analysis for Fatty Acids .4
Liquid Chromatography .5
Cholesterol Determination .6
Beta-Oxidation

CPT 1 & 2: Carnitine palmitoyltransferase 1 & 2

 Steps of Beta-Oxidation
1. Fatty acids enter a cell via fatty acid protein transporters on the cell surface
called fatty acid translocase (FAT/CD36), tissue specific fatty acid transport
proteins (FATP) and plasma membrane bound fatty acid binding protein
(FABP).
2. Inside the cell, a CoA group is added to the fatty acid by fatty acyl-CoA
synthase (FACS), forming acyl-CoA
3. Carnitine palmitoyltransferase 1 (CPT1) converts acyl-CoA to acylcarnitine
that allows the fatty acid to be transported across the inner mitochondrial
membrane via carnitine translocase (CAT) which exchanges acylcarnitines
for carnitine.
4. Inner mitochondrial membrane CPT2 then converts acylcarnitine back to
acyl-CoA. Acyl-CoA enters the fatty acid β-oxidation pathway.
5. This acetyl-CoA then enters the mitochondrial tricarboxylic acid (TCA)
cycle.
6. The NADH and FADH2 produced by both fatty acid β-oxidation and the
TCA cycle are used by the electron transport chain to produce ATP.
7. beta oxidation takes place in mitochondria releasing acetyl CoA per cycle
whereas Alpha oxidation takes place in the peroxisomes releasing CO2 per
cycle
THANK YOU