LIPID METABOLISM

Lipids:

Structure and biological function

Fat deposition in
adipose tissue
Amphipathic lipids
in cell membrane
Lipids, definition

Lipids are organic substances that are

 (physically) insoluble in water but soluble
in non-polar solvents
 (chemically) derivatives of fatty acids or
potentially capable of binding fatty acids
Some of biologically important lipids

Many kinds of lipids exist in nature, the biologically

important ones are
Fatty acids
Triacylglycerol
Pospholipids
Plasmalogen
Sphingolipids
Cholesterol
Fatty acids

Basic chemical formula of fatty acids

RCO- is the acyl group of
O Acyl group fatty acid molecule, where R
 symbolizes a hydrocarbon
R—C—OH atau RCOOH chain with the general formula
or
of CnH2n+1 (e. g. C11H23 and
C15H31).

Some example of the more common fatty acids

• Saturated fatty acids Fatty acids with no double

bond in their acyl groups are
C3H7COOH (butyric acid) called saturated fatty acids.

C11H23COOH (lauric acid)

C15H31COOH (palmitic acid)

• Unsaturated fatty acids Fattty acids containing one

CH3(CH2)7CH=CH(CH2)7COOH
CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH
double bond are called mono-
(oleic acid) unsaturated fatty acid (MUFA)
whereas those with more than
one double bond are poly-
(linoleic acid) unsaturated fatty acids
(PUFA) .
Fatty acids, biological function

Source of biological energy

Precursor of other lipids, e.g.

• triacylglycerol, phospholipids, plasmalogens,
sphyngolipids

Precursor of specialized lipid products, e.g.

• eicosanoids (prostaglandins, leucotrienes,
thromboxanes)
Triacylglycerol (TG)

Chemical formula of triacylglycerol

Acyl group
TG is the most abundant lipid
Glycerol backbone
in the universe as reflected by
its obiquitous prescence in
various animal and plant
Acyl group
tissues. This is the lipid that is
commonly known as fat.

Acyl group
In human and animal it is
quantitatively the most
Basic triacylglicerol chemical formula important depository energy
source stored mainly in the
adipose tissue. Its high
energy content and low
a molecular weight are
a particularly suitable for the
purpose. In prolonged
a starvation fatty acid released
from its molecule supplies
Molecular symbol of triacylglycerol energy requirement of most
body tissues.
Triacylglycerol (TG),
biological function

Depository energy source TG in subcutaneous adipose

tissue provides the body with
an exellent thermal insulator,
Thermal insulator preventing exessive heat loss
to cold surroundings.
Mechanical damper
TG in subcapsular adipose
tissue that envelopes importat
organs provides padding that
absorbs impact from potential-
ly injurious mechanical force.
Phospholipid, chemical formula

Kolin
Choline
Serine
Serin
Phosphatidylcholine (lecithin) Phosphatidylserine
a
a
P X

head

Ethanolamine

tail
Phosphatidylethanolamine (cephalin) Phosphatidylinositol
Inositol
Phospholipid, Phospholipid is a family of phosphate-
containing, glycerol-backboned lipids
biological that, along with other amphipathic lipids,
construct cellular membranes. It is also
function an important structural constituent of
plasma lipoproteins. Some specific
phospholipids are alveolar surfactant
that prevents pulmonary alveoli from
collapsing. Arachidonic acid derived
Structral
Structral component
component of
of biological
biological from the acyl moiety bound to the
(cellular)
(cellular) membranes
membranes second carbon of phospholipid back-
bone is the precursor of various
Structural biologically active eicosanoids.
Structural component
component of
of
lipoproteins
lipoproteins Beside the glycerol backbone and the
phosphate group, there is also an
alcohol―in the form of amino alcohol or
Lung
Lung (alveolar)
(alveolar) surfactant
surfactant carbohydrate―moiety bound to the
phosphate group of phospholipid.
Source
Source of
of fatty
fatty acids
acids as
as the
the Specific electron arrangements render
precursor
precursor of
of eicosanoids
eicosanoids the phospate group positively charged,
whereas the alcohol end tends to be of
negative charge. As such the phos-
phate-alcohol part of phosphoipid
molecules ―a.k.a. the head ― is polar
in nature and, thus, miscible with water
(hydrophylic), whereas the rest of the
molecule (“tail”) is hydrophobic.
Molecules containing both hydrophobic
and hydrophylic groups are said to be
amphipathic.
Plasmalogen
Structurally, plasmalogen
with its glycerol backbone
and phosphate-alcohol moiety
closely resembles phospho-
lipid exept for the alkyl
instead of acyl group that is
bound to the first carbon of
the glycerol backbone. It is
one of the amphipathic lipids

Sphingolipid
in cellular membranes.

Sphingolipid is another amphi-

Ceramide pathic lipid component of cell
membrane. The molecular
backbone of this lipid family
Sphingosine is not a glycerol moiety as in
phosholipid and plasmalogen
but a long chain alcohol,
known as sphingosine, to
which the hydrophylic phos-
phate-alcohol head and a
Fatty acid single hydrophobic acyl tail
are attached.
Phosphate
The sphingosine-acyl complex
is also known as ceramide.
Sphyngomyeline is a specific
sphingilipid where the alcohol
moiety is choline.
Sphyngomyeline Choline
Cholesterol

Cholesterol Steroid core (cyclopentano

perhhydrophenantrene)

 Cholesterol is a specific lipid of the cyclopentano perhydrophenantrene

family that exists exclusively in human and animal .
 The hydroxyl (-OH) group of cholesterol is miscible in water (hydrophylic)
while the four-ring cyclopentanoperhydrophenantrene moiety is hydro-
phobic.This amphiphatic property makes it suitable to function as the
structural component of cellular membrane.
 When an acyl moiety of fatty acid is esterified to the -OH group of
cholesterol, the molecule is converted to cholesteryl ester and loses its
hydrophylic head and, as such, is no more amphipatic.
 As such, cholesterol
Cholesterol is vitaland
is vital to human to human and animals.
animal since We can
it is an integral partnot exist
of their
without it. On the
cell membrane andnegative side,ofthis
the precursor substance
steroid hormones. canWebecan
dangerous
not exist to
withoutsince
health it. On prolonged
the negativeelevation
side, this of
substance can be dangerous
its concentration to health
is correlated
sincepahological
with prolonged elevation of itseg.
conditions, concentration is correlated
atherosclerosis withstone.
and gall pathological
conditions, eg. atherosclerosis and gall stone.

Cholesterol, biological function

• Structural component of (human and animal) cell membrane

• Precursor of steroid hormones, bile acids and vitamin D.
Structures
Structures formed
formed by
by amphipathic
amphipathic lipids
lipids immersed
immersed in
in aqueous
aqueous
phase
phase
Energy generation from lipids
Note on biological energy
• Basically, energy can neither be created nor
eliminated. It can only be transformed to other
forms of energy.
• The universal, readily usable energy of living
matters are chemical energy stored in phosphate-
containing substances, particularly ATP.
• ATP is produced by oxidizing energy-source
substances in a stepwise, controllable fashion,
where ATP is eventually synthesized through
oxidative phosphorilation in the mitochondrial
respiratory chain.
• In glycolysis and TCA cycle, but not in b-
oxidation, ATP can also be synthesized directly
by transfering high energy phosphate group from
phosphate-containing substrate to ADP
(substrate-level phosphorilation).
 Principle of ATP formation
Energy source
Oxidation (dehydrogen-
ation) and processing of
energy source to produce
acetyl-CoA

Propagation of reducing
equivalents along the
respiratory chain resuting
in the generation of ATP
(oxidative phoshorilation)
Respiratory chain

Further oxidation of
acetyl-CoA in TCA cycle,
producing ATP through
Acetyl-CoA
substrate-level phos-
phorilation

Respiratory chain
propagation of reducing
equivalents released in
some reaction steps of TCA
TCA cycle also produces cycle
ATP (oxidative phos-
phorilation)
 b-Oxidation
Stage I
 

Stage II
b-Oxidation is the metabolic
pathway that catabolizes fatty acid
to acetyl-CoA with the generation of
ATP. It can be visualized to occur in
three stages.
In the first stage that takes place
outside the mitochondrial matrix,
fatty acid is activated by substituting
the terminal –OH group with an
coenzyme A moiety (-SCoA). This
preliminary stage utilizes energy
from ATP to “fix” –SCoA to the acyl
moiety of fatty acid. 
In the second stage acyl-CoA is
translocated into the mitochondrial
matrix by a transporter system. 
Stage III
The two oxidation reactions of
b-oxidation themselves (in the
form of dehydrogenation rect-
ions) occur during the third
stage. The 1st dehidrogenation
 uses FAD whereas the 2 nd 
utilizes NAD+ as the reducing
equivalent (H+ and e-) acceptor.
It is the subsequent propagation
of these reducing equivalents
along the respiratory chain that
drives the mitochondrial ATP
 synthase enzyme to catalyze
ATP formation (oxidative
phosphorilation).
The final step of b-oxidation
sequence  involves another
coenzyme A that split 3-keto-

acyl-CoA into acetyl-CoA and
acyl-CoA (thiolysis) . Acetyl-CoA
are further oxidized in TCA
cycle to CO2 and H2O, generat-
ing additional ATP. The newly
formed acyl-CoA is indis-
 tinguishable from the acyl-CoA
originally activated from fatty
acid, exept for the two-carbon
shorter molecule size and, thus,
can re-enter reaction steps 
through. The cycle repeats
again and again until the entire
length of the molecule has
been cut into acetyl-CoAs.
Energetics of b-oxidation
• The quantity of ATP produced in b-oxidation depends on
the chain length of the fatty acid molecule. The longer the
fatty acid molecule is, the higher the number of oxidation
cycle (reaction steps  through in the previous slide)
and the more abundant the acetyl-CoA will be. These two
factors determine how much ATP is ultimatetely generated.
• To calculate the exact number of ATP molecules produced
from a specific fatty acid molecule you have to count how
many times the oxidation cycle repeats itself and how many
acetyl-CoA molecules are formed where each cycle forms
four ATPs and each acetyl-CoA makes ten.
Regulation of b-oxidation,
the carnitine transporter system
Like other metabolic pathways, b-oxid-
ation is subject to regulation, adapting
to the ever-changing metabolic require-
ment of the body. The regulatory enzy-
me that determine the overall rate of
this metabolic pathway is carnitine
palmitoyl transferase I that reside in the
outer mitochondrial membrane. This
enzyme is part of the carnitine trans-
porter system that move activated fatty-
acid (acyl-CoA) from cytosol into the
mitochondrial matrix. Other components
of the transporter system are carnitine
palmitoyl-transferase II, acyltransferase
and carnitine.
Insulin, through its effect in increasing
malonyl-CoA level, indirectly inhibits this
enzyme and therefore lowers b-oxid-
ation rate. (Actually, it is malonyl-CoA
that is the allosteric inhibitor of carnitin
palmitoyl-transferase I). In starvation
and other metabolic conditions where
insulin level is low b-oxidation rate is
increased (except in erythrocyte and
the brain) and fatty acid is used as the
main energy source in preference to
glucose.
Biosynthesis of fatty acid,
triacylglycerol,
and phospholipid
Fatty acid synthesis
1. de Novo syntheis of fatty acids
2. Fatty acid chain elongation
3. Desaturation of fatty acids
Fatty acid synthesis lies on the ana-
bolic segment of lipid metabolism.
Unlike glycolysis, it is not primarily
intended to fulfill the metabolic require-
ment for fatty acid. Instead, it is mainly
used to convert excess energy to fatty
acid to be subsequently attached to
glycerol backbone and stored as triacyl-
glycerol. This energy conservation
scheme is evolutionarily important since
energy is essentially precious to all
living matters and it is only in the form
of triacyglycerol that energy can be
stored in large amount .
The human body has three ways to
synthesize fatty acid. With de novo syn-
thesis excess glucose, after entering
the glycolytic pathway and converted to
acetyl-CoA is trasformed to palmitic
acid. This saturated sixteen-carbon fatty
acid and other fatty acids can further be
elongated (or shortened) through chain
elongation process, or desaturated by
the addition of double bond (s) on its R-
moiety.
The general scheme of de novo
fatty acid synthesis
Fatty acid synthesis lies on the ana-
bolic segment of lipid metabolism.
Unlike glycolysis, it is not primarily
intended to fulfill the metabolic require-
ment for fatty acid. Instead, it is mainly
used to convert excess energy to fatty
acid to be subsequently attached to
glycerol backbone and stored as triacyl-
glycerol. This energy conservation
scheme is evolutionarily important since
energy is essentially precious to all
living matters and it is only in the form
of triacyglycerol that energy can be
stored in large amount .
The human body has three ways to
synthesize fatty acid. With de novo syn-
thesis excess glucose, after entering
the glycolytic pathway and converted to
acetyl-CoA, and excess ketogenic
amino acids after beeing converted to
acetyl-CoA, are trasformed to palmitic
acid. This saturated sixteen-carbon fatty
acid and other fatty acids can further be
elongated (or shortened) through chain
elongation process, or desaturated by
the addition of double bond(s) on its R-
moiety.
 de Novo synthesis of fatty acid
The precursor substance for de novo fatty acid
synthesis is acetyl-CoA derived from glycolysis and
catabolism of some amino acids. The process itself
resembles the reverse of b-oxidation and most of the
intermediates are similar to those of b-oxidation. But
the similarity is only superficial since it takes place in
the cytosol as contrasted to the intramitochondrial
location of b-oxidation. Moreover the responsible
ezymes are also different and it takes reducing
equivalent donor (NADPH) instead of acceptor (FAD
or NAD+).
Beside the precursor acetyl-CoA, de novo synthesis
also involves malonyl-CoA as the two-carbon unit
agent to elongate the original acetyl-CoA and acyl-
CoA. During the process acetyl, malonyl, and other
intemediates are bound to the fatty acid synthase
enzyme complex.
The reaction sequence begins with elongation of
enzyme bound acetyl group with two-carbon unit from
malonyl-CoA, followed by hydrogenation, dehydration,
and second hydrogenation. The resulting four-carbon
acyl group is still bound to the enzyme and the
process repeats seven times until the acyl group has
grown in length to become a sixteen-carbon moiety.
The sixteen-carbon acyl is finally released from its
attachment to the enzyme to become palmitic acid, the
end product of de novo synthesis.
de Novo synhesis is closely related to pentose phos-
phate pathway of carbohydrate metabolism, the
primary origin of NADH.
Enzymes catalyzing de novo fatty acid
synthesis
Conversion of acetyl-CoA to malonyl-CoA catalyzed by acetyl-CoA
carboxylase
Fatty acid synthase multienzyme complex
Two classes of enzymes are respons-
ible for the catalysis of de novo fatty
acid synthesis.The first one, acetyl-CoA
carboxylase, is a biotin containing
enzyme that catalyze the reaction of
acetyl-CoA with bicarbonate (HCO3-) at
the expense of one ATP molecule to
produce malonyl-CoA. (As mentioned
before, acetyl CoA derived from excess
glucose or amino acid is used as pre-
cursor for de novo fatty acid synthesis.
But some acetyl-CoA is also used to
make malonyl-CoA, the elongating units
of de novo synthesis.)
The other one is actually a seven-enzy-
me activity protein, known as the fatty
acid synthase multienzyme complex
that calalyze the reaction sequence of
de novo fatty acid synthesis mentioned
in previous slides. The multi-activity
protein itself is tetrameric with two
identical subunits.
Regulation of de novo fatty acid
synthesis
Regulation through the modulation of
enzyme activity modulation (short-term
regulation)
Citrate allosterically activates acetyl-CoA
carboxylase
Insulin activates acetyl-CoA carboxylase
via covalent modification
Long chain acyl-CoA, epinephrin, and
glucagon decrease acetyl-CoA carboxyl-
ase activity.
Regulation through the modulation of
enzyme synthesis (long-term regulation)
Insulin increases the synthesis of fatty
acid synthase multi-enzyme complex
High-fat diet decreases the synthesis of
fatty acid synthase multi-enzyme
complex
There are short-term and long-term
regulation of de novo fatty acid synthe-
sis. Short-term regulation operates via
modification of enzyme activity, and,
therefore, takes effect “instantly”. On the
other hand, long-term regulation exerts
its effect by increasing or decreasing the
synthesis of enzymes and, thus, takes
hours to days to become apparent.
Shortly after meal, there is an elevation
of citrate and insulin level, activating
acetyl-CoA carboxylase. Since insulin
stimulates glycolysis as well, it is readily
understood that after meal the meta-
bolism of the body is shifted toward the
conservation of excess energy by
channelling the superfluous glucose (and
amino acids) through glycolysis and the
formation of acetyl-CoA to the synthesis
os fatty acids that wil eventually be
stored as triacylglycerol.
It is to be noted that long term high
insulin level also induces the synthesis
of fatty acid synthase multienzyme
complex so that after some day there is
an augmentation of fatty acid (and
triacylglycrol) synthesis. It explains why
emaciated diabetic patients tend to gain
weight when they undergo insulin
therapy. The same thing applies to
people with high-fat diet.
Synthesis of triacylglycerol and phospholipids Structurally, phospholipids are very
similar to triacylglycerol and therefore
they are synthesized using predominant-
ly the same pathway. The glycerol to be
used as backbone is first activated from
glycerol to become glycerol 3-phosphate.
Fatty acids that are to be attached to the
glycerol backbone must also be
activated to become acyl-CoA. Two acyls
are then subsequently esterified to the
activated glycerol backbone to generate
phos-phatidate. From this point onward
the path for triacylglicerol and
phospholipid synthesis diverges. Third
esterification with acyl completes the
synthesis of triacylglycerol while addition
of phos-phate and alcohol moieties is
required for the synthesis of
phospholipids.
A crucial point in the synthesis of
triacylglycerol and phospholipids is the
availability of activated glycerol
backbone (glycerol 3-P) since some
tissue does not have glycerokinase
enzyme to synthe-size it from glycerol.
For example, adi-pose tissue has to
derive glycerol 3-P from
dihydroxyacetonephosphate (DHAP), an
glycolysis intermediate. That is why
triacylglycerol synthesis and storage in
adipose tissue depend on the avaibility
of glucose and glycolysis.
Triacylglycerol synthesis is accelerated
by fatty acid availability and insulin level,
and in adipose tissue, by availability of
Storage and mobilization of lipid
 Glucose 6-P

Glycolysis

Acetyl-CoA

b-
Ox
TCA id
at
io
cycle n

Acyl-CoA Glycerol 3-P

Esterification

Hormone-sensitive lipase
Lipolysis

FA FA Glycerol

Rianto
2011
To various
Glucose FA FA tissues
Chylomicron Glycerol
and VLDL Glycerol To the liver

Schematic representation of esterification and lipolysis in adipocyte

 Storage and mobilization of fatty acids As the principal energy reserve of the body, triacyl-
glycerol is dynamically stored within its depot, the
adipose tissue. There is a cycle of esterification to
store fatty acid as triacylglycerol and lipolysis to
obtain fatty acid from it in this storehouse.
In this tissue, the esterification process to synthesize
triacylglycerol is dependent on insulin level and the
Glucose 6-P
availability of glucose, the precursor of glycerol 3-P
which are in abundance in the well fed state.
Glycolysis
Lypolysis, on the other hand, is catalyzed by
Acetyl-CoA
hormone-sensitive lipase, an lipolytic enzyme that is
b-
Ox inhibited by insulin and activated by epinephrine,
TCA id

cycle
at
io
n glucagon, thyroid hormone, and caffein.
Acyl-CoA Glycerol 3-P
Esterification
Directly after meal, under the influence of high insulin
level, excess energy is converted to fatty acids and
esterified to abundant glycerol 3-P, to be stored as
Hormone-sensitive lipase triacylglycerol. At the same time, lipolysis is inhibited
Lipolysis by the high insulin level. In the fasting state, when
FA FA Glycerol insulin level has declined and glucagon is the pre-
dominat hormone, triacylglycerol synthesis slows
down and the previously stored triacylglycerol is
broken down to provide fatty acids that will be
transported to various tissues and used as source
Rianto
of energy.
2011
To various
Glucose FA FA tissues In type I diabetes mellitus, severe lack of insulin
Chylomicron Glycerol
and VLDL Glycerol To the liver depresses triacylglycerol synthesis and storage while
at the same time lowers the inhibition of lipolysis. It
explains why uncontrolled diabetic patients are
usually emaciated. Besides, the unsually high plasma
Schematic representation of esterification and lipolysis in adipocyte fatty acid level mobilized from adipose tissue in these
patients not infrequently leads to the occurence of
serious complications .
end of part I
LIPID METABOLISM

Part 2
Ketogenesis
 Ketogenesis

FA Blood circulation

FA
Liver
Glucose 6-P

Glycolysis Acyl-CoA
Acetyl-CoA
b-
Ox
TCA id
at
io
cycle n

Acyl-CoA Glycerol 3-P

Esterification

Acetyl-CoA Ketone
Hormone-sensitive lipase
Lipolysis

FA FA Glycerol

TCA
cycle
Rianto
2011
To various
Glucose FA FA tissues
Chylomicron Glycerol
and VLDL Glycerol To the liver
The pathway for ketogenesis The immediate precursor for ketogenesis is acetyl-CoA
mobilized from adipose tissue. It takes three molecules
of this substance to make acetoacetate, the first ketone
CoA body. Reduction of this substance produces b-hydroxy-
Acetyl-CoA
butirate, the second ketone body. The third one,
CoA acetone (not shown) can be formed by releasing CO 2
CoA from the acetoacetate molecule (decerboxylation).
HMG-CoA lyase is the commited enzyme responsible
for ketogenesis.
CoA
Acetocetyl-CoA Ketogenesis is mainly regulated through the availability
of fatty acid, from which its precursor, acetyl-CA is
CoA
made.The more fattyacid enters the liver, the higher the
CoA amount of ketone bodies will be. Since the majority of
fatty acids entering the liver originate from the adipose
CoA tissue, factors that boost the lypolytic rate in this tissue
will also increase fatty acid delivery to the liver and
ultimately rise ketone bodies synthesis and amount.
3-Hydroxy-3 methylglutaryl-CoA
(HMG-CoA)
That is why in fasting and starvation, where insulin level
HMG-CoA lyase is low, blood ketone level increases, in paralel with the
CoA increasing demand of this energy source. Similarly, in
uncontrolled type-I diabetes mellitus, insulin level can
be so low that blood ketone level can reach a patho-
logically high level, and as these substances are strong
organic acids, result in acidosis (diabetic ketoacidosis)
Acetoacete
with its potentially serious effects.
Its to be noted that blood ketone level is usually low in
the well fed state, as contrasted to the high fasting
level, as lypolysis is dormant due the low level of
insulin. In this state, exogenous fatty acids from the
3-Hydroxybutirate meal is transported in chylomicrons after being
(b-hydroxybutirate) converted to triacylglycerol and not as free fatty acids,
Ketone bodies synthetic pathway unlike those derived from adipose tissue.
ATP generation from ketone bodies

The conversion of some liver aceyl-CoA to

Acetyl-CoA Ketone ketones actually prevents them from being
oxydized in theTCA cycle to generate addition-
al ATP. After being made, the ketones are
directly moved out of the liver into the cir-
culation to be transported to other tissues.
TCA
cycle Wihin other tissues, ketones are converted
back to acetyl-CoA and subsequently oxydized
in the TCA cycle, generating ATP. In this way
the postponed acetyl-CoA oxydation in the
liver is eventually carried out in other tissues.
Ketones are the dominant energy source in
fasting and starvation that, along with fatty
acids, supplies the energy requirements of the
body. In prolonged fasting the brain adapts to
use ketones along with glucose as its energy
Acetyl-CoA
Ase til KoA S.Ketone
Keton sources.



Daur
TCA
Krebs
cycle

Pemakaian senyawa keton. Di berbagai

Interorgan lipid transport
an
Overview

• Lipids are basically insoluble in water

• In the body lipid must be transported from organ to organ
• The circulatory system connecting the various organs
contains an essentialy hydrophylic aqueous plasma
immiscible with lipid.
• To be able to be transported through the hydrophilic
circulatory system, the hydrophobic lipids must be packed
and transported in a specialized structure known as
lipoproteins
• Lipoproteins are spheric structures in the plasma
consisting of an inner hydrophobic core containing the
hydrophobic lipids, enveloped by an amphipathic skin
composed of phospholipids, cholesterol, and apoproteins
• There are five major lipoprotein calasses in the plasma,
each differs in size, chemical composition, and function.
 General structure of lipoproteins

Core
Skin

Phospholipid Triacylglycerol
Cholesterol Cholesterol ester
Major plasma lipoproteins
Chylomicron is formed in the intestine to
transport dietary lipids from the intestine.
The transported triacylglycerol is delivered
to the peripheral tissues after being hydro-
lyzed to fatty acid and glycerol by the
capillary lipoprotein lipase enzyme. The
remaining lipoprotein, known as the chylo-
• Chylomicron micron remnant, with its remaining lipid
content is finally taken wholly by the liver.
• VLDL VLDL is the lipoprotein that transports
endogenous lipids made by the liver and
• IDL some of the lipids brought into the liver by
chylomicron remnant, from the liver to
• LDL varios peripherasl tissues. The transport
route closely resembles that of chylomi-
• HDL cron, with the involvement of lipoprotein
lipase. IDL is the “VLDL remnant” ana-
logue of chylomicron remnant. It is formed
during the lipoprotein lipase lipoysis of
.VLDL triacylglycerol. But IDL exists only
in a very short time, to be directly con-
verted to LDL. It is easily understood,
therefore, that cholesterol is the major
constituent lipid in LDL since the much of
the triacylglycerol cargo has been unload-
ed from its parent lipoprotein, VLDL. As
such. LDL is the lipoprotein from which
the various tissus get most of its
cholesterol.
HDL is the smallest lipoprotein in the
plasma, with the important function to
transport excess cholesterol in tissues
back to the liver to be excreted via the
biliary system
 EXOGENOUS LIPID TRANSPORT

NASCENT
CHYLOMICR
ON

TG
CE

TG
TG
CE CE
PL

HDL
CHYLOMICR
ON FATTY
ACID

CHOLESTER
OL
FATTY ACID
CE
(TG)
GLYCEROL
CHYLOMICR
ON REMNANT

EXOGENOUS LIPID TG=TRIACYLGLYCEROL, CE= CHOLESTEROL

ESTER
TRANSPORT WITH HDL
INTERACTION PL=PHOSPHOLIPID

MODIFIED FROM HARPER’S A=APOPROTEIN A, B-48 = APOPROTEIN B-48

C=APOPROTEIN C, E=APOPROTEIN E
BIOCHEMISTRY
Cholesterol uptake by tissues
Pengangkutan lipid endogen
3
Cholesterol synthesis (stage I) Tissues of the body get the cholesterol it
needs by synthesizing it and from
exogenous dietary source. Conceptually,
biosynthesis of cholesterol divided into
three stages.
In the first stage acetyl-CoA, its precursor,
is converted to malonyl-CoA, a six-carbon
product. HMG CoA reductase catalyzing
the conversion of HMG-CoA to mevalon-
ate is the most important enzyme in the
regulation of cholesterol biosynthesis and
it is this enzyme that determine the overall
rate of cholesterol production. It is inhibit-
ed by cholesterol itself . This way, the end
product controls its own producion via
feedback inhibition. Some of the choles-
terol-lowering drugs act by inhibiting this
enzyme .On the other hand, insulin
enhances the activity of this There is a
diurnal cycle where cholesterol biosynte-
sis is most active in the evening and at
night , to slow down in the morning and in
the afternoon.
In the second stage mevalonate is con-
verted to squalene, a thirty-carbon
compound. ATP and NADPH is required in
this stage.
The tird stage invoves a ring closure to
form the steroid core, chain shortage,
hydroxyl group addition, and double bond
reduction, where NADPH is neede.
Cholesterol synthesis (stage II)
Cholesterol synthesis (stage III)
Cholesterol conversion to bile acids
Cholesterol excretion via the biliary system
A portion of body cholesterol, after being
brouhgt into the liver, is excreted as such
into the biliary system, and leaves the
body with the feces. The remaining is
converted to bile acids and excreted into
the biliary system, along with their parent
cholesterol . Most of the cholesterol and
bile acids are then reabsorbed from the
intestinal lumen (the entero-hepatic
circulation) and only approximately 1% of
the original cholesterol and bile acids
finally get out of the body.
end of part 2