The chief dietary sources of lipids in human beings:

Animal source: Dairy products like milk, butter,

ghee,etc. meat and fish, especially pork, eggs.
Vegetable source: Various cooking oils from various
seeds, viz. sunflower oil, groundnut oil, cotton seed oil,
mustard oil, etc. and fats from other vegetable sources.
Vegetable fats are superior to animal fats
because:
They contain more of polyunsaturated fatty acids
Vegetable fats are less likely to go rancid due to presence of
antioxidants.
 They delay the rate of emptying of
stomach presumably by way of the hormone
enterogastrone, which inhibits gastric
motility and retards the discharge of bolus
of food from the stomach.
Thus fats have a high satiety value.
cholecystokinin
 Secretion of pancreatic juice is stimulated by the:
Passage of an acid gastric contents (acid chyme) into
the duodenum
By secretion of the GI hormones, secretin and CCK-
PZ.
Secretin: Increases the secretion of
electrolytes and fluid components of pancreatic
juice.
Pancreozymin of CCK-PZ: Stimulates the
secretion of the pancreatic enzymes.
Cholecystokinin of CCK-PZ: Causes
contraction of the gallbladder and discharge the
bile into the duodenum. Discharge of bile is also
stimulated by secretin and bile salts themselves.
Hepatocrinin: Released by the intestinal
mucosa stimulates more bile formation which is
relatively poor in the bile salt content.
 Pancreatic
juice has
been shown
to contain a
number of
lipolytic
enzymes:
Pancreatic
lipase
(steapsin)
Phospholipa
se A2
(Lecithinase)
Cholesterol
esterase
acyl CoA:monoacylglycerol acyltransferase
(MGAT)
 This pathway (the
microsomal system)
elongates saturated and
unsaturated fatty acyl-CoAs
(from C10 upward) by two
carbons, using malonyl-CoA
as acetyl donor and NADPH
as reductant, and is catalyzed
by the microsomal fatty
acid elongase system of
enzymes
 Lipogenesis converts surplus glucose and intermediates such
as pyruvate, lactate, and acetyl-CoA to fat, assisting the
anabolic phase of this feeding cycle.
Lipogenesis is depressed under conditions of restricted caloric
intake, on a fat diet, or when there is a deficiency of insulin, as
in diabetes mellitus.
These latter conditions are associated with increased
concentrations of plasma free fatty acids, and an inverse
relationship has been demonstrated between hepatic
lipogenesis and the concentration of serum-free fatty acids.
Lipogenesis is increased when succrose is fed instead of
glucose because fructose bypasses the phosphofructokinase
control point in glycolysis and floods the lipogenic pathway.
 Acetyl-CoA carboxylase is an allosteric enzyme and is activated
by citrate, which increases in concentration in the well-fed
state and is an indicator of a plentiful supply of acetyl-CoA, and
long-chain acyl-CoA inhibits its activity.
Acyl-CoA may also inhibit the mitochondrial tricarboxylate
transporter, thus preventing activation of the enzyme by
egress of citrate from the mitochondria into the cytosol.
Acyl-CoA causes an inhibition of pyruvate dehydrogenase by
inhibiting the ATP-ADP exchange transporter of the inner
mitochondrial membrane, which leads to increased
intramitochondrial [ATP]/[ADP] ratios and therefore to conversion
of active to inactive pyruvate dehydrogenase.
Insulin activates acetyl-CoA carboxylase whereas glucagon and
epinephrine have opposite actions.
 Fatty acids with an odd number of carbon atoms
are oxidized by the pathway of -oxidation,
producing acetyl-CoA, until a three-carbon
(propionyl-CoA) residue remains.
This compound is converted to succinyl-CoA, a
constituent of the citric acid cycle.
Hence, the propionyl residue from an odd-chain
fatty acid is the only part of a fatty acid that is
glucogenic.
Peroxisomes Oxidize Very Long Chain Fatty
Acids and leads to the formation of acetyl-CoA
and H2O2 (from the flavoprotein-linked
dehydrogenase step), which is broken down by
catalase.
These enzymes are induced by high-fat diets and
in some species by hypolipidemic drugs such as
clofibrate.
The exhalation of acetone is Ketone bodiesare three chemicals that
responsible for the characteristic are produced when fatty acids are
"fruity" odour of the breath of broken down in excess.
persons in ketotic states.
 First step Reverse of
Thiolase (-oxidation).
Second step
Synthesis of HMG
CoA. These reactions
are mitochondrial
analogues of the
(cytosolic) first two
steps of cholesterol
synthesis.
Third step HMG CoA
Lyase.
 Ketone bodies are
transported from the liver
to other tissues, where
acetoacetate and -
hydroxybutyrate can be
reconverted to acetyl-CoA
to produce energy.
The brain gets its energy
from ketone bodies when
insufficient glucose is
available (e.g. fasting).
only 26 mol of ATP are
produced when
acetoacetate is the end
product
only 21 mol when 3-
hydroxybutyrate is the end
product.
 Carnitine deficiency
in the newbornand especially in preterm infants
Hypoglycemia, impaired fatty acid oxidation and lipid
accumulation
muscular weakness
Treatment is by oral supplementation with
carnitine
CPT-I deficiency: only the liver
CPT-II deficiency affects primarily skeletal
muscle and, when severe, the liver
 Jamaican vomiting sickness
caused by eating the unripe fruit of the akee tree , which contains the
toxin hypoglycin.
inactivates medium- and short-chain acyl-CoA
dehydrogenase, inhibiting -oxidation and causing
hypoglycemia.
The sulfonylurea drugs (glyburide [glibenclamide]
and tolbutamide), used in the treatment of
type 2 diabetes mellitus, reduce fatty acid oxidation
and, therefore, hyperglycemia by inhibiting CPT-I.
 Higher than normal quantities of ketone bodies present in the
blood or urine constitute ketonemia (hyperketonemia) or
ketonuria, respectively. The overall condition is called
ketosis.
Acetoacetic and 3-hydroxybutyric acids are both
moderately strong acids and are buffered when present in
blood or other tissues.
However, their continual excretion in quantity progressively
depletes the alkali reserve, causing ketoacidosis. This may
be fatal in uncontrolled diabetes mellitus.
Linoleic and -linolenic acids are known as the
nutritionally essential fatty acids.
Arachidonic acid can be formed from linoleic
acid (the substrate for prostaglandin synthesis).
The desaturation of fatty acids occurs in the ER
membranes as well
Double bonds can be introduced at the 4, 5,
6, and 9 positions in most animals, but never
beyond the 9 position.
In contrast, plants are able to synthesize the
nutritionally essential fatty acids by introducing
double bonds at the 12 and 15 positions.
Additional double bonds introduced into
existing monounsaturated fatty acids are
always separated from each other by a
methylene group (methylene interrupted)
except in bacteria.
 MONOUNSATURATED FATTY ACIDS ARE
SYNTHESIZED BY A 9 DESATURASE
SYSTEM
Humans have carbon 9, 6, 5 and 4 desaturases,
but lack the ability to introduce double bonds from
carbon 10 to the end of the chain.
This is the basis for the nutritional essentiality of
the polyunsaturated linoleic and linolenic acids.
The electrons transferred from the oxidized fatty
acids during desaturation are transferred from the
desaturases to cytochrome b5 and then NADH-
cytochrome b5 reductase.
These electrons are uncoupled from mitochondrial
oxidative phosphorylation and, therefore, do not
yield ATP
Several tissues including the liver are
considered to be responsible for the
formation of nonessential
monounsaturated fatty acids from
saturated fatty acids.
MONOUNSATURATED FATTY
ACIDS ARE SYNTHESIZED BY 9
DESATURASE SYSTEM in the endo
plasmic reticulum will catalyze the
conversion of palmitoyl-CoA or
stearoyl-CoA to palmitoleoyl-CoA or
oleoyl-CoA
SYNTHESIS OF
POLYUNSATURATED FATTY ACIDS
INVOLVES DESATURASE &
ELONGASE ENZYME SYSTEMS
 Linoleic is especially important in that it is required for the
synthesis of arachidonic acid.
Arachidonate is a precursor for the eicosanoids (the
prostaglandins, thromboxanes, and leukotrienes).
It is this role of fatty acids in eicosanoid synthesis that leads
to poor growth, wound healing, and dermatitis in persons on
fat-free diets.
Also, linoleic acid is a constituent of epidermal cell
sphingolipid that functions as the skins water permeability
barrier.
The 3 major omega-3 fatty acids utilized by human tissues
are ALA (-Linolenic Acid), EPA (Eicosa Pentaenoic Acid), and
DHA (Docosa Hexaenoic Acid).
 Most of the ALA consumed in the
diet comes from plant sources
such as flax seed, walnuts,
pecans, hazelnuts, and kiwifruit.
A small percentage of omega- 3
PUFAs come from meats
common to Western diets such
as chicken and beef.
ALA can serve as the precursor
for EPA and DHA synthesis in
humans.
Most of the omega-6 PUFAs
consumed in the diet are from
vegetable oils such as soybean
oil, corn oil, borage oil, and acai
berry and consist of linoleic acid.
 The most important omega-6 PUFA is arachidonic
acid.
When cells are stimulated by a variety of external
stimuli, arachidonic acid is released from cell
membranes through the action of phospholipase
A2 (PLA2).
Arachidonate then serves as the precursor for the
synthesis of the biologically active eicosanoids,
the prostaglandins (PG), thromboxanes (TX),
leukotrienes (LT), and lipoxins (LX).
 The most important role of the omega-3 PUFAs, EPA,
and DHA, is that they serve as the precursors for potent
anti-inflammatory lipids called resolvins and protectins.
Omega-3 PUFAs bind to and activate peroxisome
proliferatoractivated receptor- (PPAR). Activation of
PPAR results in activation of hepatic fatty acid
oxidation.
Omega-3 PUFAs also inhibition of hepatic fatty acid
synthesis reduction in the expression levels of hepatic
fatty acid synthase (FAS) and acetyl-CoA carboxylase
(ACC), 2 critical enzymes of fatty acid synthesis.
 Arachidonate, which may be
obtained from the diet, but is
usually derived from the
position 2 of phospholipids in
the plasma membrane by the
action of phospholipase A2 is
the substrate for the
synthesis of the PG2, TX2
series (prostanoids) by the
cyclooxygenase pathway, or
the leukotrienes (LT), and
lipoxins (LX) series by the
lipoxygenase pathway, with
the two pathways competing
for the arachidonate
substrate
 Prostaglandins, thromboxanes
and leukotrienes, are collectively
known as eicosanoids to reflect
their origin from polyunsaturated
fatty acids with 20 carbons.
Potent compoundsphysiologic
(inflammatory response) and
pathologic (hyper sensitivity).
Eicosanoids are not stored, and
they have an extremely short
half-life, being rapidly
metabolized to inactive products.
Their biologic actions are
mediated by plasma membrane
G proteincoupled receptors
HHT,
hydroxyheptadecatrienoat
e

Prostaglandin endoperoxide synthase

(PGH synthase)
 Two isozymes: COX-1 and COX-2.
COX-1 is made constitutively in
most tissues, and is required for
maintenance of healthy gastric
tissue, renal homeostasis, and
platelet aggregation.
COX-2 is inducible in a limited
number of tissues in response to
products of activated immune
and inflammatory cells the
pain, heat, redness, and
swelling of inflammation, and
the fever of infection.
hydroperoxyeicosatetraenoic acid (HPETE)

Prostaglandins Potential therapeutic
uses:
prevention of conception,
induction of labor at term,
termination of pregnancy,
prevention or alleviation of gastric
ulcers,
control of inflammation and of blood
pressure,
relief of asthma and nasal congestion.
PGD2 is a potent sleep-promoting
substance.
Thromboxanes are synthesized in platelets
and upon release cause vasoconstriction and
platelet aggregation.
Their synthesis is specifically inhibited by
low-dose aspirin.
Prostacyclins (PGI2) are produced by blood
vessel walls and are potent inhibitors of
platelet aggregation.
Slow-reacting substance of anaphylaxis
(SRS-A) is a mixture of leukotrienes C4, D4,
and E4. This mixture of leukotrienes is a
potent constrictor of the bronchial airway
musculature.
These leukotrienes together with leukotriene
B4 also cause vascular permeability and
attraction and activation of leukocytes and
are important regulators in many diseases
involving inflammatory or immediate
hypersensitivity reactions, such as asthma.
 Phospholipids are the predominant lipids
of cell membranes.
In membranes, the hydrophobic portion
of a phospholipid molecule is associated
with the nonpolar portions of other
membrane constituents, such as
glycolipids, proteins, and cholesterol.
Non-membrane phospholipids serve
additional functions in the body, for
example, as components of lung
surfactant and essential components of
bile, where their detergent properties
aid in the solubilization of cholesterol.
 The hydrophilic (polar) head of the phospholipid
extends outward, interacting with the
intracellular or extracellular aqueous
environment.
Membrane phospholipids also function as a
reservoir for intracellular messengers, and,
for some proteins, phospholipids serve as
anchors to cell membranes.
There are two classes of phospholipids:
those that have glycerol (from glucose) as a
backbone are called glycerophospholipids
(or phosphoglycerides).
those that contain sphingosine( from serine
and palmitate).
 Glycerophospholipids are formed The
phosphate group from phosphatidic acid
(PA) can be esterified to another compound
containing an alcohol group :
Serine + PA phosphatidylserine
Ethanolamine + PA
phosphatidylethanolamine (cephalin)
Choline + PA phosphatidylcholine (lecithin)
Inositol + PA phosphatidylinositol
Glycerol + PA phosphatidylglycerol
The conversion of PS to PC first requires
decarboxylation of PS to yield PE; this then
undergoes a series of 3 methylation
reactions utilizing S-adenosylmethionine
(SAM) as methyl group donor.
 This pathway is located in peroxisomes.
Dihydroxyacetone phosphate is the
precursor of the glycerol moiety of
glycerol ether phospholipids.
Plasmalogens, which comprise much of
the phospholipid in mitochondria, are
formed by desaturation of the
analogous 3-phosphoethanolamine
derivative.
Platelet activating factor (PAF) (1-alkyl-
2-acetyl-sn-glycerol-3-phosphocholine)
is synthesized from the corresponding
3-phosphocholine derivative.
 Three major classes of plasmalogen
have been identified: choline,
ethanolamine, and serine
plasmalogens.
Ethanolamine plasmalogen is
prevalent in myelin.
Choline plasmalogen is abundant in
cardiac tissue.
One particular choline plasmalogen
has been identified as an extremely
powerful biological mediator, capable
of inducing cellular responses, is
called platelet-activating factor, PAF.
 PAF activates inflammatory cells and mediates
hypersensitivity, acute inflammatory, and
anaphylactic reactions.
It causes platelets to aggregate and
degranulate, and neutrophils and alveolar
macrophages to generate superoxide radicals.
PAF is one of the most potent bioactive
molecules known, causing effects at
concentrations as low as 10-12 mol/L.
 Two molecules of PA esterified through
their phosphate groups to an
additional molecule of glycerol is
called cardiolipin, or
diphosphatidylglycerol
A phospholipid present in mitochondria
is cardiolipin (diphosphatidylglycerol).
Cardiolipin, found in the inner
membrane of mitochondria, is
specifically required for the functioning
of the phosphate transporter and for
cytochrome oxidase activity , and is
also thought to be involved in
programmed cell death (apoptosis).
Sphingomyelin, a sphingosine-based
phospholipid, is a major structural lipid in the
membranes of nerve tissue.
A ceramide containing a fatty acid 30 carbons
long is a major component of skin, and regulates
 Glycosphingolipids, containing
sphingosine and sugar residues as
well as fatty acid, do not contain
phosphate and found in the outer
leaflet of the plasma membrane
with their oligosaccharide chains
facing outward, form part of the
glycocalyx of the cell surface and
are important
a) in cell adhesion and cell
recognition;
b) as receptors for bacterial toxins
(eg, the toxin that causes cholera);
and
c) as ABO blood group substances. Gal =galactose; Glc=
gucose;
GalNAc =N-
acetylgalactosamine;
 Ceramide is an important signaling molecule (second
messenger) regulating pathways including apoptosis
(processes leading to cell death), cell senescence, and
differentiation, and opposes some of the actions of
diacylglycerol.
Glycosphingolipids (cerebrosides) are
galactosylceramide (GalCer) and
glucosylceramide (GlcCer).
GalCer is a major lipid of myelin, whereas GlcCer
is the major glycosphingolipid of extraneural tissues
and a precursor of most of the more complex
glycosphingolipids.
Globoside is a type of glycosphingolipid with more than
one sugars as the side chain (or R group) of ceramide.
Sphingolipids are degraded by lysosomal enzymes.
Deficiencies of these enzymes result in a group of lysosomal
storage diseases known as the sphingolipidoses.
Globoside is a type of glycosphingolipid with more than one sugars as the side chain (or R group)
of ceramide.
Sphingolipids serve in intercellular communication ,as the antigenic determinants of the ABO blood group, as
receptors by viruses and bacterial toxins
 The major constituents of surfactant are
dipalmitoylphosphatidylcholine,phosphatidylglycerol,
apoproteins (surfactant proteins: Sp-A,B,C), and
cholesterol.
Deficiency in the synthesis of surfactant respiratory
distress syndrome (RDS) of a premature infant.
These components of lung surfactant normally contribute
to a reduction in the surface tension within the air spaces
(alveoli) of the lung, preventing their collapse.
The premature infant has not yet begun to produce
adequate amounts of lung surfactant.
 Phospholipases hydrolyze the phosphodiester bonds of
phosphoglycerides, with each enzyme cleaving the
phospholipid at a specific site.
 Sphingomyelin is degraded by
sphingomyelinase, a
lysosomal enzyme that
hydrolytically removes
phosphorylcholine, leaving a
ceramide.
The ceramide is, in turn,
cleaved by ceramidase into
sphingosine and a free fatty
acid
PAPS= 3-phosphoadenosine 5-phosphosulfate (an active sulfate donor)

(globoside)

P-
D
U al
G
 Four major groups of lipoproteins have
been identified that are important
physiologically and in clinical
diagnosis. These are
1) Chylomicrons, derived from intestinal
absorption of triacylglycerol and other
lipids;
2) Very Low Density Lipoproteins (VLDL,
or pre--lipoproteins), derived from the
liver for the export of triacylglycerol;
3) Low-Density Lipoproteins (LDL, or -
lipoproteins), representing a final stage in
the catabolism of VLDL; and
4) High-Density Lipoproteins (HDL, or -
lipoproteins), involved in VLDL and
chylomicron metabolism and also in
cholesterol transport.
 Apolipoproteins carry out several roles:
(1) they can form part of the structure of the
lipoprotein, eg, apo B;
(2) they are enzyme cofactors, eg, C-II for
lipoprotein lipase, A-I for lecithin:cholesterol
acyltransferase, or enzyme inhibitors, eg, apo
A-II and apo C-III for lipoprotein lipase, apo C-I
for cholesteryl ester transfer protein;
and (3) they act as ligands for interaction with
lipoprotein
 LCATand the LCAT
activator apo A-Ibind to
the discoidal particles,and
the surface phospholipid
and free cholesterol are
converted into cholesteryl
esters and lysolecithin.
The non-polar cholesteryl
esters move into the
hydrophobic interior of the
bilayer, whereas lysolecithin
is transferred to plasma
albumin.
A non-polar core is
generated, forming a
spherical, pseudomicellar
HDL covered by a surface
film of polar lipids and
apolipoproteins
 20+ years of studies:
Patients with smaller LDL size have greater CHD risk
at any given level of LDL-C.
Lower risk Higher risk

130 mg/dL 130 mg/dL

Large LDL Small LDL

(Pattern A) LDL
(Pattern B)
Cholesterol
Balance
But they also
have more
particles!
 Fatty livers fall into two main categories.
The first type is associated with raised levels of plasma free fatty acids
resulting from mobilization of fat from adipose tissue or from the
hydrolysis of lipoprotein triacylglycerol by lipoprotein lipase in
extrahepatic tissues.
The production of VLDL does not keep pace with the increasing influx
and esterification of free fatty acids, allowing triacylglycerol to
accumulate, causing a fatty liver.
This occurs during starvation and the feeding of high-fat diets.
The ability to secrete VLDL may also be impaired (eg, in starvation).
In uncontrolled diabetes mellitus, twin lamb disease, and ketosis in
cattle, fatty infiltration is sufficiently severe to cause visible pallor (fatty
appearance) and enlargement of the liver with possible liver dysfunction.
 The second type of fatty liver is usually due to a metabolic
block in the production of plasma lipoproteins, thus
allowing triacylglycerol to accumulate.
Theoretically, the lesion may be due to
(1) a block in apolipoprotein synthesis,
(2) a block in the synthesis of the lipoprotein from lipid and
apolipoprotein,
(3) a failure in provision of phospholipids that are found in
lipoproteins, or
(4) a failure in the secretory mechanism itself.
 Nonalcoholic fatty liver disease
(NAFLD) is the most common
liver disorder worldwide.
When accumulation of lipid in the
liver becomes chronic,
inflammatory and fibrotic changes
may develop leading to
nonalcoholic steatohepatitis
(NASH), which can progress to
liver diseases including cirrhosis,
hepatocarcinoma, and liver
failure.
 Alcoholic fatty liver is the first stage in alcoholic liver
disease (ALD) which is caused by alcoholism and
ultimately leads to cirrhosis.
Changes in the [NADH]/[NAD+ ]
Oxidation of ethanol by alcohol dehydrogenase leads to
excess production of NADH.
The increased [NADH]/[NAD+ ] ratio also causes
increased [lactate]/[pyruvate], resulting in
hyperlacticacidemia, which decreases excretion of uric
acid, aggravating gout.
 Some metabolism of ethanol takes place via a
cytochrome P450-dependent microsomal
ethanol oxidizing system (MEOS) involving
NADPH and O2 .
This system increases in activity in chronic
alcoholism.
Ethanol also inhibits the metabolism of some
drugs, eg, barbiturates, by competing for
cytochrome P450-dependent enzymes.
 MALATE-ASPARTATE RESPIRATORY INHIBITED of
NADH/NAD+
SHUTTLE CHAIN TCA CYCLE

GLYCEROL 3-P INHIBITED of

GLUCONEOGENESIS
LACTATE/PYRUVATE ACETYL-CoA
HYPOGLYCEMIA

LACTIC ACIDOCIS LIPOGENESIS

FFA
KETOGENESIS
EXCRETION of TRIACYLGLYCEROL
URIC ACID CHOLESTERO
HYPERLIPIDEMIA GENESIS
KETOSIS
HYPERURICEMIA FATTY LIVER
HYPERCHOLESTEROL
 Deficiency of choline
(lipotropic factor).
The antibiotic
puromycin,
ethionine(-amino--
mercaptobutyric acid),
carbon tetrachloride,
chloroform,
phosphorus, lead, and
arsenic.
Orotic acid also
causes fatty liver; it
is believed to
interfere with
glycosylation of the
lipoprotein, thus
inhibiting release, and
may also impair the
recruitment of
triacylglycerol to the
particles.
Adipose tissue secretes hormones such as adiponectin, which modulates glucose and lipid metabolism
in muscle and liver, and leptin, which regulates energy homeostasis.
 Brown adipose tissue is the
site of nonshivering
thermogenesis. It is found in
hibernating and newborn
animals and is present in small
quantity in humans.
Thermogenesis results from
the presence of an uncoupling
protein, thermogenin, in the
inner mitochondrial membrane.
 Cholesterol is present in tissues and in plasma either as
free cholesterol or as a storage form, combined with a
long-chain fatty acid as cholesteryl ester.
Cholesterol is an amphipathic lipid and as such is an
essential structural component of membranes and of the
outer layer of plasma lipoproteins.
It is synthesized in many tissues from acetyl-CoA and is
the precursor of all other steroids in the body such as
corticosteroids, sex hormones, bile acids, and vitamin D.
As a typical product of animal metabolism, cholesterol
occurs in foods of animal origin such as egg yolk, meat,
liver, and brain.
 Stage 1 Biosynthesis of
Acetyl CoA (C2)
cholesterol
HMG-CoA
NADPH rate-determining step
HMG-CoA
Reductase cholesterol is feedback inhibitor
NADP+
Mevalonate (C6) mevalonate is feedback inhibitor
target site for statin drugs
Stage 2 Stage 4
Stage 3
Mevalonate Lanosterol (C30)
Squalene (C30)
3ATP
3ADP CO2 O2 Cyclization O2 (19 steps)
Active Isoprenoids (C5) NADPH Squalene NADPH
NADPH Several epoxidase/
Condensation Steps NADP+
cyclase NADP+ 3 CH3
NADP+ Lanosterol (C30) Cholesterol (C27)
Squalene (C30) (4-ring structure)

The ER is the primary site of cholesterol synthesis

HMG-CoA reductase, the key
rate-limiting enzyme in the
cholesterol biosynthetic
pathway.
XANTHELASMA
 Significant reductions of plasma cholesterol can be
effected medically by the use of cholestyramine
resin or surgically by the ileal exclusion operations.
Both procedures block the reabsorption of bile acids,
causing increased bile acid synthesis in the liver.
This increases cholesterol excretion and up-regulates
LDL receptors, lowering plasma cholesterol.
Sitosterol is a hypocholesterolemic agent that
acts by blocking the absorption of cholesterol from the
gastrointestinal tract.
 The formation of
cholesterol at various
stages in the
biosynthetic pathway.
The statins inhibit
HMG-CoA reductase,
thus up-regulating LDL
receptors.
Statins currently in use
include atorvastatin,
simvastatin, and
pravastatin.
 Fibrates such as clofibrate and gemfibrozil act mainly to
lower plasma triacylglycerols by decreasing the secretion of
triacylglycerol and cholesterol-containing VLDL by the liver.
In addition, they stimulate hydrolysis of VLDL triacylglycerols
by lipoprotein lipase.
Probucol appears to increase LDL catabolism via receptor
independent pathways, but its antioxidant properties may be
more important in preventing accumulation of oxidized LDL,
which has enhanced atherogenic properties, in arterial walls.
Nicotinic acid reduces the flux of FFA by inhibiting adipose
tissue lipolysis, thereby inhibiting VLDL production by the liver.
 Type of LDL bound to ApoB and Apo(a)
Prothrombotic
Binding domain similar to plasminogen, may
compete, favoring thrombosis
Proatherogenic
preferentially binds oxidized phospholipids and
taken up into atheromatous plaques
ACSLs = Acyl-CoA Synthetase Long chains
ATGL= Adipocyte Triacylglycerol Lipase
FATPs= Fatty Acid Transport Proteins