LIPIDS, DERIVED & COMPLEX

LIPIDS:
-STRUCTURE
- FUNCTIONS
BIOCHEMISTRY

1
"BIOCHEMISTRY?

Penelitian/ investigation hubungan molekul-
kehidupan

Menggunakan prinsip kimia untuk menjelaskan biologi

Kita tahu bahwa "Semua organisme hidup mematuhi
hukum-hukum kimia dan fisika yang sama. Hidup ini
kompleks, dinamis, terorganisir dan mandiri. Hidup ini
berbasis seluler dan informasi. Hidup beradaptasi dan
berkembang


2
GENERAL OBJECTIVES
By the end of this unit, students should be able to:
Classify lipids according to their structures
Relate the structure of lipids to their functions

3
SPECIFIC OBJECTIVES
1. Structure and Classification of Lipids
At the end of this lecture, students should be able to:
Give the general classification of lipid
Describe lipid classification according to their structure
Describe the structure of fatty acids
Understand the nomenclature of fatty acids
Describe the structure of triacylglycerol
Describe the structure of phospholipids
Describe the structure of sphingolipids;
Describe the structure of Derived Lipids eg
eicosanoids/prostaglandins
Describe the structure of different types of steroids,
cholesterol
Describe the structure of Lipoproteins; ketone bodies

4
2. Functions of Lipids
At the end of this lecture, students should be able to:
Describe the functions of different types of lipids:
Fatty acid
Triacylglycerol
Phospholipid; sphingolipids
Cholesterol
Eicosanoids/Prostanoids
Lipoproteins; ketone bodies

5
Lipids : general informations

Is third major classes of macromolecules.
Water-insoluble organic compounds.
High solubility in nonpolar organic solvents.

Consist of a number of subclass:
1. Fatty acids and their derivatives, the eicosanoids.
2. Triacylglycerols.
3. Wax esters important in external structure so no detailed discussion
4. Phospholipids.
5. Sphingolipids; Phosphosphingolipids.
6. Isoprenoids: steroids;
7. Lipoproteins & ketone bodies
Perform diverse functions. Examples:
1. Important structural components in cell membrane, controls flow of
materials
2. As fat (in adipose tissue), store energy efficiently.
3. Chemical signals (=hormones), vitamins or pigments assisting/membantu
biological process.
4. Outer coatings of various organism (the waxes).

Structural relationships of the major classes
of lipids
7
Classifications according to main groups:
Fatty acids Glycerides
- saturated - neutral
- unsaturated -phosphoglycerides

Complex lipids Nonglycerides
- lipoproteins - sphingolipids
- glycolipids - steroids
- waxes
8
1.Fatty acids and their derivatives
Fatty acids (f.a):
- are long chain carboxylic acids, the common ones are C
14
- C
20
- 2 kinds, saturated and unsaturated. Unsaturation can be mono, di or tri.
- Unsaturation normally begins at C
9
.
In di unsaturation, the second is at C
12
.
- The cis-isomer are the regular ones C= C
R R
-

number of

unsaturation is denoted by 2
nd
number in the symbol to
describe a fatty acid (xy:z)
The presence of cis configuration causes an inflexible (rigid) kink in
the chain making unsaturated fatty acids loosely packed than saturated
fatty acids thus melting point saturated f.a > unsaturated f.a. e.g at
room temperature, palmitic acid (16:0)is a solid whereas palmitoleic acid
(16:1) is a liquid.

maximum
9
Liquids at RT
10
Polar head
Hydrophobic tail
11
Mammals obtain most of their f.as from dietary sources. They can
synthesize saturated f.as and small amount of monounsaturated f.as.
Two types: Nonessential FAs(= FAs can be synthesized) and Essential
FAs must be obtained from the diet.
Common Essential FAs are the di (18:2) and tri (18:3) unsaturated or
generally referred as PolyUnsaturatedFatty Acids (PUFAs)
2 PUFAs : n-3 PUFAs and n-6 PUFAs
n-3 PUFAs are the -3 and n-6 PUFAs are the -6 fatty acids
Rich sources of essential FAs (EFAs) are veg. oil, nuts & seeds. EFAs
have several critical physiological functions. Individuals with deficiency
of EFAs show symptoms of dermatitis, poor wound healing, reduced
resistance to infection, alopecia and thrombocytopenia.
Linoleic(18:2) and linolenic(18:3) acids are precursor of several
important metabolites.
Linoleic acid plays an important role in lowering cholesterol levels

12
Myristic (14:0)and palmitic acids (16:0) (in eukaryotes) found
covalently bonded to proteins, i.e acylated proteins. The f.a tail
helps the protein membrane to interact with the hydrophobic
environment.
F.as are transported from fat cell as acyl serum proteins to body cell
via acyl transfer reactions.
In RCOO form, -R interact with non-aqueous region and -COO
interact with aqueous, good as emulsifying agent
Arachidonic Acid
(AA)
20 : 4 5,8,11,14-eicosatetraenoic acid Liver fats
EPA 20 : 5 5,8,11,14,17-eicosapentaenoic
acid
fish oil
Behenic acid 22 : 0 docosanoic acid rapeseed oil
Erucic acid 22 : 1 13-docosenoic acid rapeseed oil
DHA 22 : 6 4,7,10,13,16,19-docosahexaenoic
acid
fish oil
13
DHA (docosahexaenoic acid; 22:6) and AA (arachidonic acid 20:4)
- are both crucial to the optimal development of the brain and eyes.
The importance of DHA and AA in infant nutrition is well
established.
- both substances are routinely added to infant formulas.
- Excessive amounts of omega-6 polyunsaturated fatty acids and a
very high omega-6/omega-3 ratio have been linked with
pathogenesis of many diseases eg cardiovascular disease, cancer,
and inflammatory and autoimmune diseases.
- The ratio of omega-6 to omega-3 in modern diets is approximately
15:1,
- ratios of 2:1 to 4:1 have been associated with reduced mortality
from cardiovascular disease, suppressed inflammation in patients
with rheumatoid arthritis, and decreased risk of breast cancer.
- may be better to increase the consumption of omega-3 fatty acids
rather than decrease the consumption of omega-6 fatty acids
because a reduction of polyunsaturated fats in the diet would
increase the incidence of cardiovascular disease.

14
When f.a molecules are added to water, the non-polar tails of the
molecules clump into the center of a ball like structure called a
micelle, because they are hydrophobic or "water hating".
The polar head of the molecule presents itself for interaction with the
water molecules on the outside of the micelle

15
Reactions:
Fatty acid undergoes usual reaction of acids eg.
- esterification
RCOOH + RCH
2
OH RCOOCH
2
R + H
2
O
- acid base
RCOOH + NaOH RCOO
+
Na
-
+ H
2
O
In practical this reaction is acid number
Reaction at C=C bonds. These reaction are used (at industrial level)
to produce a particular product
i- for production of margerine: hydrogenation.
OR
ii- for quality control purposes
a- Iodine value in practical
b- saponification number

H
+
16
Eicosanoids:
They are prostaglandins, prostacyclins, thromboxanes, leukotrienes,
and epoxyeicosatrienoic acids
are derivatives from 3 different C
20
multi-unsaturated EFAs
molecules.
The 3 twenty-carbon(C
20
) EFAs:
* Eicosapentaenoic acid (EPA), an -3 fatty acid with 5 double bonds;
* Arachidonic acid (AA), an -6 fatty acid,with 4 double bonds; most
popular precursor.
* Dihomo-gamma-linolenic acid (DGLA), an -6, with 3 double bonds
So there are 1 omega-3 (-3) and 2 omega-6(-6) EFAs.
C
20
multi unsaturated EFA (3 altogether)
EPA AA DGLA
-3
5 d.bnds
-6
4 and 3 d.bnds
Molecules formed from these 3 EFA through
various reactions = eicosaniods
17
Source of and compounds produced from arachidonate by
various pathways. Prostanoids/prostaglandins H
2
gave rise to 3
series of derivatives through 2 enzyme systems . Each series
has 3-4 members.
Enzymes system
producing the
eicosanoids from
parent molecule AA
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Prostaglandins eg PGE
2
( one of prostaglandins)
A letter code is based on ring modifications (e.g., hydroxyl or
keto groups).
A subscript refers to the number of double bonds in the two
side-chains.
They are hormones.
They have specific effects on target cells close to their site of
formation.
Synthesis and degradation pathways occurs in liver. They are
rapidly degraded, so they are not transported to distal sites
within the body.
Also involve in intracellular signal cascades.
Prostaglandins all have a cyclopentane ring. Thromboxanes have a
6-member ring.
affect other cells by interacting with plasma membrane G-protein
coupled receptors.
Depending on the cell type, the activated G-protein may stimulate
or inhibit formation of cAMP, or may activate a phosphatidylinositol
signal pathway leading to intracellular Ca++ release.
19
Structure of the major eicosanoids
20
Function of the eicosanoids :
- Mediate physiological & pathophysiological action on the liver,
protecting the stomach lining, regulating blood pressure, mediating
pain and inflammation, regulating the contraction and relaxation of
smooth muscle, and the dilation and constriction of blood vessels.
When there is an injury to the body, prostaglandins cause blood
vessels to dilate and increase their permeability to fluid and
proteins. This results in swelling and increased temperature of the
affected area. Prostaglandins also increase the sensitivity of nerve
endings to pain.
- they control i) other hormones and ii) practically all important
functions in the body, e.g. the central nervous system and the
immune system.
- so they are also known as super hormones. Thus, they are very
important for good health and well-being. There are both good and
bad eicosanoids.
- have other various roles: blood clotting, immune system modulation,
control of reproductive processes and tissue growth, and regulation
of the sleep/wake cycle.

21
exert their effects at very low concentrations and (2) usually act
near their sites of synthesis.
TXA2 is made principally by platelets. It causes vasoconstriction and
promotes platelet aggregation. These actions prevent excessive
blood loss when a blood vessel is damaged or severed. PGI2 is
made by the blood vessel wall and has the opposite effects. It
prevents intravascular platelet aggregates from forming and
obstructing blood flow.
Corticosteroids are anti-inflammatory because they prevent
inducible Phospholipase A2 expression, reducing arachidonate
release.
22
Classified under Simple Glycerolipids or neutral lipids / neutral fats
consist of the trihydric alcohol glycerol esterified with 3 molecules of
long-chain fatty acids (esters of glycerols with 3 FAs molecules).
The FAs are of varying lengths and may be saturated, unsaturated
or a combination.

2. Triacylglycerols (TAG).
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Glycerol
Back-bone
Fatty acids
1,3-diacylglycerol
1-monoacylglycerol
C18:1

C16:0
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2 types of TAG
i)Simple Glycerides: When the 3 FAs are similar .
ii) Mix Glycerides. When the 3 FAs are different. Mix glycerides are more
common.
TAG are also referred to as fats or oils.
Fats are solid TAG at RT, contain large proportion of saturated FAs.
Oils are liquid TAG at RT, contain high proportion of unsaturated FAs.
TAGs have no charge.
Glycerol esterified with 1 FAs (mono glyceride) or 2 FAs (diglyceride)
normally present only in small amounts. They are metabolic intermediates.
In fruits and seeds, TAGs are important energy reserve. Seed rich in oil
include peanut, corn, palm and etc.
TAG store fatty acids as fats in animal bodies. Complete oxidation of 1 g
of fat yield~ 38.9 kJ. Carhohydrates yields 17.2 kJ/g
Before fat can be oxidized, it must be hydrolysed to acid anion and
glycerol.
Hydrolysis can be by i) Enzyme ( by lipases)
ii) chemical, base eg NaOH => saphonification
25
CH
2
CH
CH
2
O
O
O C
O
C
O
C
O
R3
R3
R3
3 NaOH
CH
2
CH
CH
2
OH
OH
OH
+
NaO C
O
R3
a soap, Na or K
salt of a fatty acid
3
Saphonification ( base hydrolysis of TAG)
** In the body, bile acid ( = natural soap) derived from cholesterol
26
fat, play important role (i) as storage and transport of f.acids. Fat are
stored in adipose tissue in cells called adipocytes. Fat is anhydrous
(hydrophobic nature) therefore for an X quantity of energy only
occupies 1/8 th of glycogens volume.
(ii) is to provide insulation in low temperatures due to its poor heat
conductor property.
TAGs are lipid in human diet. Broken down/hydrolyse by lipases.
Lipases are synthesized in the pancreas and secreted into small
intestine.
Pancreatic lipase catalyzes hydrolysis of the primary esters (at C1 and
C3 of TAG).
TAG exhibit rancidity (change taste and smell) on long keeping. How?
Cause can be by i) hydrolytic/enzyme
ii) oxidative ( more common with unsaturated f.as)
i) CH
2
-OCOR1 CH
2
OH
CH-OCOR2 CHOH + 3 RCOOH
CH
2
-OCOR3 CH
2
OH
Enz/H
2
O
orgnsm
Responsible for change of
taste/smell
27
Oxidative rancidity: common at C=C in PUFAs
ii) CH
2
-OCOR1 CH
2
OCOR1
o
CH-OCOR2 CHOCOR2
o

CH
2
-OCOR3 CH
2
OCOR3
o


O
2
o
Free radical
Oxidized lipids
28
A mixture of I and a number from 2
I
I is esters of fatty acids and fatty alcohols
2
3. WAXES
29
A thin layer that cover the leaves of plants or provide a surface
coating for insects or the skin of animals
Technologist referred to commercial products of mineral, marine,
plant and insect origin that contain fatty materials of various kinds
A number of waxes are produced commercially in large amounts for
use in cosmetics, lubricants, polishes, surface coatings, inks and
many other applications.
Examples: Beeswax; on leaves of plants( jojoba, carnauba); wool
wax
waxy material from plant is microcrystalline in structure. It is the
interface between the plant and the atmosphere. It serves many
purposes, for example to limit the diffusion of water and solutes,
while permitting a controlled release of volatiles that may deter
pests or attract pollinating insects. The wax provides protection
from disease and insects, and helps the plants resist drought.

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4.Phospholipids
Is a fat derivatives, having hydrophobic and hydrophilic domains.
Also referred as phosphoglycerides
its simplest form, one glycerol bonded to two fatty acids and a
phosphate group e.g (i) phosphotidic acid or
(ii) phosphate group carrying one of several nitrogen-containing
molecules, choline e.g phosphatidylcholine (= phosphoglycerides)
A major component of the cell membranes.
phospholipids are always needed for the formation of a stable bilayer
structure
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CH
2
CH
CH
2
O
O
O P
O
C
O
C
O
R1
R2
OH
O
Phosphatidic acid
=> phosphoacylglycerol
Phosphoric acid ester
CH
2
CH
CH
2
O
O
O P
O
C
O
C
O
R1
R2
OR
O
Phosphatidic ester
32
CH
2
CH
CH
2
O
O
O P
O
C
O
C
O
R1
R2
OR
O
R=
CH
2
CH
2
NH
3
+
phosphatidylethanolamine
CH
2
CH
2
N(CH
3
)
3
+
phosphatidylcholine
(lecithin)
CH
2
CH
OH
CH
2
OP
O
O
OCH
CH
2
O
O
C
O
C
O
R3
R4
diphosphatidylglycerol
(cardiolipin)
Phosphatidyl esters, egs.
33
A phosphatidylcholine or lecithin
34
Phosphatidylcholine phosphatidylserine
Phosphatidylethanolamine Phosphatidylinositol
Various phosphoglycerides
35
The phosphate carrying one of several nitrogen-containing
molecules with presence of ve and +ve charges usually is referred
as hydrophilic polar head group and the 2 fatty acyl chains is
referred as hydrophobic tail.











suspended in water, they spontaneously
rearrange into ordered structures
36
When many phospholipid molecules are placed in water, their
hydrophilic heads tend to face water and the hydrophobic tails are
forced to stick together (basis for membrane structure), forming a
bilayer (membrane) or ball-like structures called micelles.
/ bilayer vasicle
37
suspended in water, they spontaneously
rearrange into ordered structures
38
5. Sphingolipids
The sphingolipids, like the phospholipids, are composed
of a polar head group and two nonpolar tails. The core
of sphingolipids is either the long-chain amino alcohol,
sphingosine or its N-acyl derivative ( a ceramide)
are found in plants and animals,
are common in the nervous system.
Consist of 2 sub groups:
i- sphingomyelin
ii- glycosphingolipids/ glycolipids (cerebrosides, sulfatides,
globosides and gangliosides ) They contain no
phosphate. The carbohydrate ( glucose or galactose) is
linked to the alcohol of the lipid via glycosidic bond.
They are found in the cell membrane of nerve and brain
cells
39
40
Sphingomyelins
Sphingomyelins are
important structural lipid
components of nerve cell
membranes.
They are molecules of
ceramide with phosphoester
at C1 of the ceramide core
structure
The predominant
sphingomyelins contain
palmitic or stearic acid N-
acylated at carbon 2 of
sphingosine.

41
Structure of galactocerebrosides
42
Gangliosides
Are sphingolipids with one or more sialic residues
Names include M-mono, D-di, T- tri (# residues) and
subscripts for number of sugars attached to the ceramide.


GM
2


O
CH
2
OH
O
O
OH
O
Sph O
CH
2
OH
OH
OH
O
O
CH
2
OH
O H
OH
NH
C O
CH
3
O
R
N
H
OH
COO
-
C
O
CH
3
R =
CH OH
CH OH
CH
2
OH
43
Cardiac Glycosides are - :
- drugs used in the
treatment of congestive
heart failure and cardiac
arrhythmia.
- are found as secondary
metabolites in several
plants, but also in some
animals.
-increases the force of
cardiac muscle contraction.
Eg Digitoxin from digitalis
purpure
O
CH
3
O
OH
O
O
CH
3
CH
3
3
44
6.Isoprenoids
Are biomolecules that contain repeating 5-C
structural units (isoprene units)
This class of lipids includes:
i) Steroids only discuss this.
ii) Terpenes
iii) Lipid vitamines
45

(i) STEROIDS

Steroids are complex derivatives of triterpenes They are characterized
by a carbon skeleton consisting of four fused rings referred to as
Cyclopentano perhydro phenanthrene.
Steroids are nonpolar.
The most abundant steroid is cholesterol.
Cholesterol is the precursor for all steroids. It is a common component
of animal cell membranes and functions to help stabilize the
membrane. Thus it is a crucial molecule in animals.
*high levels of it in the blood may contribute to atherosclerosis.

Cyclopentano perhydro phenanthrene
46
They were made by joining together isoprene units, usually in a head-
to-tail.
For cyclic compounds, the linkage is followed by the additional linkage
to form the ring.
Terpene are classified according to the number of C they contain.






The body produces more cholesterol from diet that has high content of
saturated fat.


Isoprene unit.
(2-methyl-1,3-butadiene),
47
Structures of several
steroids
Steroid hormones are
chemical messanger.
Steroid hormones can
be divided into 5
classes:
1. glucocortocoids
2. mineralocorticoids
3. androgen
4. estrogens
5. progestins



48
Ketones Bodies
Refer to 3 compounds: acetone, acetoacetate, and beta-
hydroxybutyrate
Are toxic acidic chemicals.
Are soluble in the body fluid.
Formed in mitochondria of liver cell.
its synthesis ( breakdown of fats, especially f.f.as) occurs in
response to low glucose/insulin in the blood or after exhaustion of
glycogen.
Are formed when Acetyl-CoA is present in excess of the amount
needed for TCA cycle (i.e ATP/NADH
2
production cycle)
When only small amount of k.b are formed the phenomenon is
referred to as KETOGENESIS
when excess accumulate, this abnormal state is called KETOSIS.
This is not necessarily harmful.
Accumulation of large amounts of ketone bodies can lower bodys
pH to dangerously acidic levels, this state is called
KETOACIDOSIS.
Ketoacidosis is very rare, and, in general, happens only in untreated
Type I diabetes
49
KETOGENESIS
3-hydroxy-3-methyl-glutaryl-CoA
50
51
Regulation
When the body has no free carbohydrates (eg. glucose) available,
fat must be broken down into acetyl-CoA ie active -oxidation of
fatty acid occurs in order to get energy. But Acetyl-CoA is not being
recycled through the citric acid cycle because the citric acid cycle
intermediates (mainly oxaloacetate) have been depleted to feed the
gluconeogenesis pathway, and the resulting accumulation of acetyl-
CoA activates ketogenesis.
Diabetic patient
52
Lipoproteins
There are 2 main forms: Low density lipoproteins (LDL)
High density lipoproteins (HDL)

Low density lipoproteins (LDL) carry cholesterol from liver to the
cells

High density lipoproteins (HDL) returns the extra cholesterol that is
not needed to the liver.

53
Lipoproteins
Is a conjugate (complex of one or more component of
lipids and apo- protein) rendering lipids solubility in the
blood/cytosol. Generally, in particle form
The particles range in size from 10 to 1000 nm
The proteins are in the surface layer and being
hydrophilic renders solubility to the conjugate.
The lipids may be covalently or non- covalently bound to
protein
Is the form by which various lipid components(
fig.1a,b&c) are transported within the body system
either for special function or elimination
differ in the ratio of protein to lipids, and in the particular
apoproteins and lipids that they contain
Density increases with increase % of protein
54
The interaction of the proteins portion with (a)
enzymes in the blood, (b) with each other and (c) with
specific proteins on the surfaces of cells determine which
lipid molecule will be added to or removed from the
lipoprotein particles.
Abnormalities of the amounts or kinds of lipoproteins in
blood or in many other arteries could lead to
atherosclerosis
*atherosclerosis is sometimes referred to as hardening or
narrowing of the arteries, cholesterol deposition, or
arterial blockage. Atherosclerosis in the coronary arteries
could lead to heart attack, angina or coronary pain, or
sudden death, and atherosclerosis in many other arteries
in the body could lead to stroke, aneurysm, or gangrene.

55
Apoproteins
Generally are Amphipathic -helices (polar along one
surface of a helix and hydrophobic along the other side)
are common structural alignment.
Types are:
- Apolipoprotein A-I (apoA-I) found in HDL and
Chylomicron; consisting of N-terminal antiparallel 4-
helix bundle & C-terminal -helical chain.
-truncated apoA-I : shorter, lacks 1-43 amino acid of the
native apoA-I. Also HDL associated
- Apoprotein B-48: major protein in nascent chylomicron
-Apoprotein B-100: found on VLDL, IDL and LDL ;major
protein of LDL, recognizes and binds to LDL receptor on
liver; one of the longest known proteins in human.
56
- Apoprotein CII : found on chylomicrons, activates
Lipoprotein Lipase leading to hydrolysis of fatty acid
from Tag.
- Apoprotein C I-III: found on VLDL, IDL and HDL, and
Chylomicrons;
- Apolipoprotein E (apoE): found on VLDL, IDL and HDL
and chylomicron, associated with late-onset Alzheimer's
disease

CLASSIFICATION of Lipoproteins:
As b-clam CONJUGATE
As CHYLOMICRONS *
As density-base LIPIDS: 4 types *
i) VLDL ii) IDL iii) LDL iv) HDL

* these are 5 lipoproteins found in blood
57
b-clam Conjugate
- Found within intestinal cells; are fatty acids bound with
the intestinal fatty acid binding protein (I-FABP)
secluding f.acids from the cytosol. I-FABP are also found
in several cell types, have a ''b-clam" structure.
The fatty acid is carried in a cavity between 2
approximately orthogonal -sheets, each consisting of 5
antiparallel -strands.
* In blood, free fatty acids are transported bound to blood
albumin
58
As CHYLOMYCRON
- assembled in the intestinal mucosa as a means to
transport dietary cholesterol and triacylglycerols (tag)
and other lipid components, to organs and the rest of the
body.
- Contain least amount of protein and largest amount of
lipids: 1-2% protein, 85-88% triglycerides, ~8%
phospholipids, ~3% cholesteryl esters and ~1%
cholesterol. So tag is highest % of the lipids
- Largest in size and least dense of all lipoproteins
- Secreted by intestinal epithelial cells, and transported via
the lymphatic system to the blood for transport to liver,
skeletal muscle and adipose tissue.
59
60
-The apoproteins that predominate before the chylomicrons
enter the circulation include apoB-48 and apoA-I, A-II
andA- IV. ApoB-48 combines only with chylomicrons.
- In the bloodstream, chylomicrons acquire apoC-II and
apoE from plasma HDLs.
in the capillaries of adipose tissue and skeletal muscle it
is partly hydrolyzed to free fatty acids and glycerol by the
action of lipoprotein lipase and remainder is
chylomycron remnant
the free fatty acids are then absorbed by the cells and
the glycerol is returned via the blood to the liver (and
kidneys). The glycerol is then converted to the glycolytic
intermediate DHAP.

61
62
+
B-48
Apo A-I,
A-II
A- IV
Chylomicron in lympatic system
tag
;
cholesterol
Liver
Adipose Tissue
Skeletal Muscle
Apo C-II & E
(from plasma HDL)
Mature Chylomicron in blood
blood
lymph
;
Diet
Intestinal
tissues
1- dietary tag emulsified with bile salt soluble
2-degraded by pancreatic lipases(1 and 3 positions sequentially) generate
free fatty acids and a mixtures of mono- and diacylglycerols(1,2-
diacylglycerols and 2-acylglycerols)& lysophospholipid
3-absorption of the products of pancreatic lipases by the intestinal mucosal
cells
4-resynthesis of triacylglycerols and phospholipid
5-combine with specific protein chlomicron
phospholipids
f.f + glycerol +
chylo remnt
+lipoprotein
lipase
Key
63
**Summary: chylomycron is a class of lipoproteins that transports
(dietary) cholesterol and triglycerides from the small intestines to
tissues after meals. Synthesised in the intestinal mucosa and carried
via the intestinal lacteals and lymphatic system to the blood stream ,
they are then degraded to chylomicron remnants in the capillaries of
muscles and adipose tissues through cleavage of the majority of
their triglycerides by endothelial lipoprotein lipase. These remnants
are rapidly cleared by the liver by receptor-mediated endocytosis .

64
As Density-based lipid ( more proteins more dense). Types are:
- Very low density lipoprotein, VLDL,
- Intermediate density lipoprotein, IDL
- Low density lipoprotein, LDL
- High density lipoprotein, HDL

1. VLDL
- packet of triacylglycerols, tag (newly synthesized from excess dietary
fat and carbohydrates) released into lymphatic system/blood from
liver for delivery to muscle and adipose tissue.
- Also contain some cholesterol and its esters and the apoproteins:
apoB-100, apoC-I, apoC-II, apoC-III and apoE. VLDLs acquire
apoCs and apoE from circulating HDLs.
-The fatty acid portion of VLDLs is released to adipose tissue and
muscle through the action of lipoprotein lipase
- During its life, loses certain apoCs to HDL. ApoB-100 and apoE
remain as predominant protein.
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2. IDL
- is intermediate density lipoprotein.
- is intermediate between VLDL and Low density
lipoprotein(LDL)
- formed from VLDL. When VLDL loses the fatty acid
portion to the action of lipoprotein lipase, and loses
portion of apoC (transferred to HDL)
- also referred to as VLDL remnant
- Either forms LDL when more tag is lost
- Or can be direct-uptake by the liver when interacted with
the LDL receptor through formation of complex then
endocytosed. For LDL receptors in the liver to recognize
IDLs requires the presence of both apoB-100 and apoE
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3. LDL
Forms when IDL loses more tag
Consist of highly-hydrophobic core of polyunsaturated
fatty acid linoleate and about 1500 cholesteryl ester
molecules. This core is surrounded by a shell of
phospholipids and cholesterol, and a single copy of B-
100 protein
apolipoprotein B-100 is the exclusive apoprotein
component. It is a 4536 a.a polypeptide chain
contains 20-22% protein, 10-15% triglycerides, 20-28%
phospholipids, 37-48% cholesteryl esters and 8-10%
cholesterol.
carry cholesterol from the liver to cells of the body for
further use.
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The uptake of LDLs occurs predominantly in liver (75%),
adrenals and adipose tissue.
In the uptake, the endocytosed membrane vesicles
(endosomes) fuse with lysosomes, in which the
apoproteins are degraded and the cholesterol esters are
hydrolyzed to yield free cholesterol.
makes up more than half of the total lipoprotein in
plasma
are the primary plasma carriers of cholesterol for
delivery to all tissues
are taken up by cells via LDL receptor-mediated
endocytosis
the interaction of LDLs with LDL receptors requires the
presence of apoB-100

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The cholesterol is then incorporated into the plasma
membranes as necessary. Excess intracellular cholesterol
is re-esterified by acyl-CoA-cholesterol acyltransferase
(ACAT), for intracellular storage. The activity of ACAT is
enhanced by the presence of intracellular cholesterol.
Sometimes referred to as the bad cholesterol"
lipoprotein
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4. HDL
are synthesized de novo in the liver and small intestine,
as primarily protein-rich disc-shaped particles free of any
cholesterol and cholesteryl esters .
The primary apoproteins of HDLs are apoA-I, apoC-I,
apoC-II and apoE
a major function is to act as circulating stores of apoC-I,
apoC-II and apoE.
collects cholesterol from the body's tissues, and brings it
back to the liver. Sometimes referred to as the "good
cholesterol" lipoprotein
carry approximately one-fourth of the total amount of
cholesterol in blood (the total cholesterol level measures
blood cholesterol in all lipoproteins)

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Recommended Levels
*Units: milligrams per deciliter (mg/dl).
Lipoprotein Desirable High Desirable
parameter in atherosclerotic
patient

Cholesterol <200 >240 <200
Triglycerides <200 >400 <200
LDL Costerol <130 >160 <100
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In 1990 another lipoprotein, called lipoprotein(a) was
discovered
In many people, it circulates in the blood in very small
amounts.
20% and 30% of people in the U.S. have lipoprotein(a)
levels high enough to raise coronary risk. Lipoprotein(a)
levels are higher among black people than among
people of white or Asian race.
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