LIPIDS

Commonly referred to as fats

Lipids are soluble in nonpolar organic solvents, such
as chloroform and ether, but relatively insoluble in
polar solvents such as water. Thus, cholesterol and
triglycerides travel in plasma not as free-floating
molecules, but as part of water-soluble complexes
called lipoproteins
Structural components of lipoproteins
Core: contains hydrophobic lipids such as cholesteryl
esters, free fatty acids and TAG
Surface: contains ampiphatic such as free (unesterified)
cholesterol and phospholipids
Hydrophobic group faces towards the core of the lipoprotein
Hydrophilic group faces towards the plasma
General Functions
Storage of energy (TAG)
Fatty acids and glycerol from hydrolysis
of TAG can enter TCA cycle to become
ATP
Cushion and shock absorber
Integral part of the cell membrane
Hormone synthesis
Cholesterol: precursor of all steroid
hormones
FORMS OF LIPIDS
TRIGLYCERIDES
CHOLESTEROL
PHOSPHOLIPIDS
FATTY ACIDS
Fat soluble vitamins
(ADEK)
 TRIGLYCERIDES
(Triacylglycerol/Neutral Fats)
They possess three molecules of fatty acids
connected to a glycerol backbone via ester
bonds.
It serves as the main storage form of lipids
in man, as insulator or shock absorber and
as integral part of the cell membrane.
When they are metabolized, the fatty acids
are released to the cells and converted into
energy.
Their breakdown is facilitated by lipases
(endothelial lipase, hepatic lipase,
lipoprotein lipase), epinephrine and cortisol.
 CHOLESTEROL
Unsaturated steroid alcohol with four rings
Free form is amphiphatic and therefore found in the
surface of lipoproteins together with phospholipids
Endogenously synthesized from acetyl-coenzyme A in
the microsomal and cytosolic compartments of the cell.
HMG-CoA reductase = the rate-limiting enzyme in
the cholesterol biosynthesis; target of statin drugs
(e.g. lovastatin, simvastatin).
Unlike other lipids, it is not readily catabolized by most
cells and therefore does not serve as a source of fuel.
Its transport and excretion is promoted by estrogen
Cholesterol
Structure
 IMPORTANCE OF CHOLESTEROL
1. Converted by the liver into primary bile acids
such as cholic acid and chenodeoxychlic acids
which promote fat absorption in the intestine
by acting as detergents
2. Precursor material for the synthesis of
steroids hormones. Converted by testes,
ovaries and adrenal glands into
glucocorticoids, mineralocorticoids, androgens
and estrogens
3. Converted to 7-dehydrocholesterol (pro vit
D3) in the skin and transformed into Vit. D3
upon irradiation from sunlight
 CHOLESTEROL
Exist in the body in two different forms:
1. Cholesteryl esters
accounts to approximately 70% of total
cholesterol of the body
cholesterol bound to a fatty acid.
Since it is not charged, it is found in the center of
lipoproteins along with triglyceride
2. Free cholesterol
accounts to approximately 30% of total
cholesterol; also known as unesterified
cholesterol.
converted by LCAT (activated by ApoA-1) into
cholesteryl esters
polar form
 Phospholipids
Structurally similar to triglyceride, except that
2 fatty acids and a phosphate group is
attached to the glycerol backbone.
It is the most abundant form of lipids that
originates in the liver and intestines.
There are several types of phospholipid
head groups (choline, inositol, serine,
ethanolamine), with phosphatidylcholine or
lecithin being the most abundant in
lipoproteins and cell membranes
Constituent of the cell membrane, contains
polar and non-polar end (amphipatic)
 Phospholipids
They alter fluid surface surface tension (surfactant) which
prevents the collapse of alveoli during expiration
Forms of phospholipids
1. Lecithin/phosphatidyl choline - 70%
mature lung: L/S ratio > 2.0
specimen for testing: amniotic fluid at third trimester
method: TLC followed by densitometric quantitation
Lamellar bodies - secretory granules in the alveoli which
contains pulmonary surfactant, produced by Type II
pneumocytes
2. Sphingomyelin - 20%
essential component of cell membranes and nerve sheet
accumulates in the liver and spleen of patients suffering
from Niemann-Pick dx (def enz. sphingomyelinase)
3. Cephalin - 10% (phosphatidylethanolamine, phosphatidylserine,
inositol phosphatide)
 FATTY ACIDS
They exist as short (4-6 C), medium (8-12 C) or long (>12 C)
linear chains of molecules that are the major constituents of
triglycerides and phospholipids.
They can be saturated (single bonds) or unsaturated (with
double bonds)
Monounsatured - 1 double ring
Polyunsaturated - >1 double ring
Minimal amount are present in the plasma and most are non-
covalently bound to albumin.
Very important source of energy
Cis and Trans FA
Cis = Hydrogen oriented in the same position, more fluid
Trans = Hydrogen oriented in different position, less fluid, not
found in nature. Produced by chemically processing lipids,
related to CHD
Cis- and Trans-Fatty Acids
 Fat-Soluble Vitamins Functions Deficiency Syndromes Toxicity
Vitamin A (retinol) A component of retinal rod Squamous metaplasia, Livers of polar bears and
pigment. Role in vision in especially glandular, large animals have very
dim light, growth; follicular hyperkeratosis; high levels of vitamin A.

Fat Soluble Vitamins

reproduction. Maintenance
of resistance to infection
xerophthalmia; night
blindness, reproductive
disorders, vulnerability to
Acute: can cause
drowsiness, headache,
vomiting, stupor, skin
infection. peeling, and papilledema.
Chronic: teratogenic,
osteoporosis,
hepatotoxicity.
Carotenoids in excess,
distinct orange-yellow skin
color.

Vitamin D Promotes absorption of Rickets in children, High intake of vitamin D,

(cholecalciferol) calcium and phosphorus;
mineralization of bones
and teeth
osteomalacia in adults,
hypocalcemia, tetany
hypercalcemia and
hypercalciuria, toxicity
above UL of 50 g. Bone
demineralization,
constipation, muscle
weakness, renal calculi

Vitamin E (tocopherol) Antioxidant, scavenges free Spinocerebellar Mild GI distress, nausea;

radicals; cellular degeneration, ataxia. coagulopathies in patients
respiration, primarily in receiving anticonvulsants
muscle, RBC integrity

Vitamin K Cofactor of procoagulants Defective clotting, bleeding Foods containing vitamin K

(phytomenadione) hepatic factors II disorder cause no toxicity
(prothrombin), VII and X, problems. Excess amounts
protein C and protein S of vitamin K may decrease
clotting time.
 LIPOPROTEINS
Large macromolecular complexes of lipids and
s p e c i a l i z e d p r o t e i n s moiety k n o w n a s
apolipoproteins.
Its main purpose is to transport triglycerides and
cholesterol to their sites of energy and utilization.
The higher the TAG content, the less dense the
LPP gets.
Surface of the lipoprotein is composed of
phospholipids and free cholesterol while the core
is composed of TAG, cholesteryl esters and fatty
acids
Size of the lipoprotein correlates with the lipid
content. The larger the lipoprotein, the more
triglycerides it contains.
 APOLIPOPROTEINS
Each lipoprotein is associated with specific apolipoprotein
Functions of apolipoproteins
1.maintain the structural integrity of lipoproteins
2.ligand for cell surface receptors
3.activation and inhibition of enzymes involved in the lipid
metabolism
Possess a structural motif called amphiphatic helix, which
accounts for the ability of these proteins to bind lipids
Apo B containing LPP
Chylomicrons, VLDL, IDL, LDL
Each LPP contains only one apo B
Non Apo B containing LPP
HDL
Apolipopro Main
Functions Comments
tein Distribution
Major structural protein of
Apolipoproteins
ApoA-I
HDL (70%)
HDL
Synthesized in the
liver and intestine;
Activates LCAT
HDL biosynthesis
Ligand for ABCA1
ApoA-II HDL
HDL, CM,
Component of intestinal
ApoA-IV free in
lipoproteins
plasma
Found exclusively on Not recognized by
ApoB-48 CM
chylomicrons LDLR
Major structural protein in Synthesized in the
VLDL
ApoB-100 VLDL and LDL liver with lipids of
LDL endogenous origin
Ligand for LDL receptor
CM
ApoC-I
VLDL

CM Deficiency causes
ApoC-II Activates lipoprotein lipase reduced clearance of
VLDL TAG-rich lipoproteins
Apolipopro Main
Functions Comments
tein Distribution
Inhibits lipoprotein lipase
ApoC-III Inhibits receptor
recognition of apo-E
E-2, E-3, and E-4
CM,VLDL isoforms; E-4 is
associated with high LDL-
Binds to LDL-receptor and IDL
ApoE C, higher risk of CHD and
remnant-receptor remnants Alzheimers disease;
HDL E-2 associated with type 3
hyperlipoproteinemia
Homologous to
Structural protein for Lp (a) plasminogen, may be
Apo (a) May inhibit plasminogen prothrombotic;
binding bound to apoB-100 by
disulfide linkage

Cell-aggregating factor in Involved in apoptosis;

Sertoli cells; linked to neurologic
ApoJ diseases like Picks and
Inhibitor of the C5b*7 Alzheimers; also known
complement complex; as clusterin
 Electrophoretic Density
Particle Major Apolipoproteins Diameter ()
Mobility* (kg/L)
Chylomicrons Origin ApoA-I, A-IV, B-48, C-I, C-II, C-III, E 750-12,000 <0.95
VLDL Pre- ApoB-100, C-I, C-II, C-III, E 300-700 0.95-1.006
IDL or pre- ApoB-100, E1.006-1.019 12-20
LDL B ApoB-100 180-300 1.019-1.063
HDL2 A ApoA-I, A-II, E 50-120 1.063-1.125
HDL3 A ApoA-II, A-I, E 50-120 1.125-1.210
Lp(a) Pre- ApoB-100, Apo(a) 1.045-1.080

HDL2, Ultracentrifugation subclass of high-density lipoprotein; HDL3, ultracentrifugation

subclass of high-density lipoprotein; IDL, intermediate-density lipoprotein; LDL,
lowdensity
lipoprotein; Lp(a), lipoprotein A; VLDL, very-low-density lipoprotein.
*Agarose gel electrophoresis.
 Classification of Lipoproteins
A. Major lipoproteins (classified based
on density)
Chylomicrons
VLDL
LDL
HDL
B. Minor lipoproteins
IDL
Lp(a)
C. Abnormal Lipoproteins
B-VLDL
LpX
 CHYLOMICRONS
It is the largest (80-1200 nm) and least dense
(<0.95) of the lipoprotein particles.
Produced in the intestines and rapidly
hydrolyzed by lipoprotein lipase in the
luminal surface of capillary endothelium to
become chylomicron remnants (TAG)
which are recognized by the liver thorough
interaction of apo E with LDL receptor on
the liver.
They acquire apo C-II (cofactor for LPL) from
plasma
They are cleared from the circulation within 6-
9 hours after, persistence after a 12-hour
fast is considered abnormal
 CHYLOMICRONS
T r a n s p o r t e x o g e n o u s / d i e t a r y
triglycerides to liver, muscles, fat depot
and peripheral tissue.
Because of their large size, they can
scatter light which causes the post-
prandial plasma to appear "milky"
Because they are very light, they form
a floating "creamy" layer when left
undisturbed for several hours
Apolipoprotein content: apoB-48,
apoA-I, apoA-IV, apoC-I, apoC-II,
apoC-III, and apoE
 VERY LOW DENSITY LIPOPROTEINS
Also known as Pre-Beta Lipoprotein
Major carrier of endogenous (hepatic-
derived) t r i g l y c e r i d e s to the
peripheral tissues
Produce "turbid" plasma when
present in high concentration
Like chylomicrons, they also scatter
light and account for most of the
turbidity of the fasting hyperlipidemic
plasma specimens
 VERY LOW DENSITY LIPOPROTEINS
They DO NOT form a creamy top layer
because they are smaller (30-70 nm)
and less buoyant (0.95-1.006) than
chylomicrons
Synthesized in the liver and contains
apo B-100, apo E, apo C-I, apo C-II
and apo C-III
Like chylomicrons, they shed TAG and
cholesterol esters by the action of
lipoprotein lipase.
 LOW DENSITY LIPOPROTEIN
Also known as Beta Lipoprotein or
Bad Cholesterol
The major end product of VLDL
catabolism.
Tr a n s p o r t c h o l e s t e r o l t o t h e
peripheral tissue.
Constitute about 50% of total
lipoproteins in the plasma.
The most cholesterol rich among
other apo B containing lipoprotein
and the most atherogenic.
 LOW DENSITY LIPOPROTEIN
Do NOT scatter light or alter the clarity of
plasma even at greatly increased
concentrations
Readily taken up by cells via the LDL receptor
on the liver and peripheral cells
Because they are significantly smaller (18-30
nm) than VLDL and chylomicrons, they can
infiltrate into extracellular spaces of the vessel
wall where they can be oxidized and taken up
by macrophage through the scavenger
receptor. Macrophage that take up too much
lipid turn into foam cells, which is the
predominant type of cell in fatty streaks, an
early precursor of atherosclerotic plaque
 HIGH DENSITY LIPOPROTEINS
Also known as the Alpha Lipoprotein and Good
Cholesterol.
It is the smallest (5-20nm) and most dense
(1.063-1.21) lipoprotein and synthesized by
both the liver and the intestines.
Cholesteryl ester within HDL is selectively
taken by the liver via the SR-B1 receptor.
Cholesterol ester transport protein (CETP) is
considered as an alternative pathway wherein
HDL disposes of its cholesterol ester content
Plays an important role in transporting excess
cholesterol from peripheral cells to the liver
(reverse cholesterol transport). This explains
the anti-atherogenic property of HDL.
 HIGH DENSITY LIPOPROTEINS
Two major ultracentrifugation subclasses:
Discoidal/nascent HDL: represent newly
secreted HDL and is the most active form in
removing excess cholesterol from tissues
Spherical HDL: formed when nascent
acquires additional cholesteryl esters and
TAG from peripheral cells; classified based
on density
HDL2 (1.063-1.125) more cardioprotective than
HDL3
HDL3 (1.125-1.21)

Apoprotein content: Apo A-I (70%),

Apo A-II and Apo E
 HDL and LDL (NCEP guidelines)

HDL Cholesterol
<40 mg/dL high risk for CHD

>60 mg/dL low risk for CHD

LDL Cholesterol
<100 mg/dL optimal

100-129 mg/dL Near optimal

130-159 mg/dL borderline high

160-189 mg/dL high

>190 mg/dL very high

 Minor Lipoproteins
1. IDL
Also known as VLDL remnants
Only exist transiently during
conversion of VLDL to LDL
TAG and cholesterol content is
intermediate between those of VLDL
and LDL
NOT typically present in normal
plasma except in type III
hyperlipoproteinemia where elevated
levels of IDL are found
 Minor Lipoproteins
2. Lp(a)
A.k.a "sinking pre-beta lipoprotein"
Electrophoresis: pre beta region
Ultracentrifugation: LDL section
LDL-like particles that contain one
molecule of apo B-100 linked to apo (a) by
a single disulfide bond
Apo (a) interfere with normal thrombolysis
by virtue of its similarity to plasminogen
increasing risk for both myocardial
infarction and stroke
 Abnormal Lipoproteins
1. Beta-VLDL (B-VLDL)
a.k.a Floating Lipoprotein
Electrophoresis: beta region
Ultracentrifugation: VLDL section
Abnormal lipoprotein that
accumulates in type 3
hyperlipoproteinemia.
Richer in cholesterol than usual
VLDL
 Abnormal Lipoproteins
2. Lp X
An abnormal lipoprotein found in patients with
obstructive biliary cirrhosis or cholestasis and in
patients with familial lecithin/cholesterol
acyltransferase (LCAT) deficiency
Phospholipids and nonesterified cholesterol are the
lipid main components (90% by weight) and albumin
and apo-C are the main protein components
Chemical Composition of Major Classes of Plasma Lipoproteins
Free Cholesterol Phospholipid
Protien (%)* Triglyceride (%)
Cholesterol (%) esters (%) (%)
Chylomicrons 1-2 1-3 2-4 80-95 3-6
VLDL 6-10 4-8 16-22 45-65 15-20
IDL Intermediate between VLDL and LDL
LDL 18-22 6-8 45-50 4-8 18-24
HDL 45-55 3-5 15-20 2-7 26-32
 Four Main Pathways of Lipid
Metabolism

Absorption Pathway
Exogenous Pathway
Endogenous Pathway
Reverse Transport Pathway
 ABSORPTION PATHWAY
1. Dietary TAG and cholesterol assembles into
large hydrophobic lipid globules until they reach
duodenum where they combine with bile salts
(from liver/gall bladder) and emulsied into
smaller and more stable micelles.
2. Micelles are acted upon by pancreatic lipase
cleaving off fatty acids from hydrophobic lipids
converting them into more polar compounds
with ampiphatic property
TAG is transformed into monoglycerides and diglycerides
Cholesteryl esters are transformed into free cholesterol
Phospholipids are transformed into lysophospholipids
 ABSORPTION PATHWAY

3. Passive absorption of
ampiphatic lipids at the intestinal
microvilli. Some active transport
occurs however.
4. Absorbed lipid are reesterified in
the ER of intestinal cells to form
TAG and cholesteryl esters
 ABSORPTION PATHWAY
5. The newly formed TAG and
cholesterol esters are combined
with nascent apo B-48 by
microsomal transfer protein (MTP)
to form chylomicrons which enters
the lacteals (mesenteric lymphatic
capillaries)
6. Chylomicrons travels through the
lymphatic duct and then enters the
bloodstream via the thoracic duct.
 ABSORPTION PATHWAY
TAG absorption is highly efficient, around
90% of TAG is taken up by the intestine
whereas only 50% of the ingested
cholesterol is taken up by the body.
ABCG5 and ABCG8 are specific
transporters that prevents excess
absorption of dietary cholesterols and plant
sterols. Defect in these transporters will
lead to a disease called sitosterolemia and
have a predisposition to atherosclerosis
and xanthomatosis because of increased
cholesterol and plant sterol absorption.
 Other Pathways
Exogenous Pathway
Chylomicrons transport exogenous
(dietary) lipids into liver and peripheral
tissues
Hydrolysis of chylomicrons into
chylomicron remnants by lipases
Endogenous Pathway
VLDL transport endogenous (hepatic)
lipids into peripheral tissues
VLDL is transformed into VLDL remnants
(IDL) and LDL
LDL transport cholesterol from liver into
peripheral tissues
Reverse Transport Pathway
HDL transport excess cholesterol form
peripheral tissues back to the liver.
 Lipolytic Enzymes and Other Proteins
CETP: Catalyze the transfer of cholesteryl
esters from HDL to apoB100-containing
lipoproteins (VLDL, LDL) in exchange of
TAG
ABCA1: Mediates the efflux of free
cholesterol from peripheral cells into
nascent HDL where it is esterified by LCAT
LCAT: Catalyzes the esterification of
cholesterol, especially in HDL, by
promoting transfer of fatty acids from
lecithin to cholesterol. Enables HDL to
accumulate cholesterol as cholesteryl
esters. Activated by apoA-I
 Lipolytic Enzymes and Other Proteins
Acyl : cholesterol acyl transferase (ACAT):
re-esterifies excess cholesterol for storage
LPL: Hydrolysis of TAG in lipoproteins (esp.
VLDL and CM), releasing free fatty acids and
glycerol to tissues to be used as energy or
reesterified by ACAT for storage as TAG.
ApoC-II are essential cofactor.
Hepatic TAG lipase: Expressed on liver and
adrenal glands. Primarily converts IDL to LDL
LDL receptor: Recognizes Apo B-100 found
on LDL, IDL, VLDL and Apo E found on
chylomicrons and VLDL remnants
 ARTERIOSCLEROSIS
Due to deposition of LDL-c in artery walls
leading into formation of fatty streaks
which are precursors of atherosclerotic
plaques.
Atherosclerotic plaques can partially block
or occlude blood flow when it ruptures and
can lead to
Peripheral vascular disease (PVD) if plaques
rupture in the arteries of arms and legs
Coronary artery disease (CAD) if plaques
rupture in the heart; associated with angina
and myocardial infarction
Cerebrovascular disease (CVD) if plaques
rupture in the brain; associated with stroke
Xanthomas: nodules in the skin due to
deposition of excess lipids
DISEASES OF LIPIDS AND LIPOPROTEINS
A. High Cholesterol with High LDL-c
B. High Triglycerides with Normal
Cholesterol
C. High Triglycerides with High
Cholesterol
D. Low Total Cholesterol and
Triglycerides
E. Isolated Low HDL-C
F. Isolated high HDL-C
DISEASES OF LIPIDS AND LIPOPROTEINS
A. High Cholesterol with High LDL-c
Hyperbetalipoproteinemia (LDL-c, Normal TAG)
Defect in LDL receptor, Apo B
1. Polygenic (Nonfamilial Hypercholesterolemia)
Cause of hypercholesterolemia is multifactorial
Term to describe patients who develop age-related increases in
cholesterol that do not respond to lifestyle modification.
Accounts for approximately 85% of all cases of
hypercholesterolemia
2. Familial Hypercholesterolemia
Autosomal dominant disorder caused by one of several
mutations in the LDL-receptor gene.
Homozygotes: 1 in 1 million (800-1,000 mg/dL)
Heteroygotes: 1 in 500 (300-600 mg/dL)
DISEASES OF LIPIDS AND LIPOPROTEINS
3. Familial Defective ApoB
Autosomal dominant disorder of the apoB
gene that interferes with the recognition
of apoB-100 by the LDL receptor
4. Sitosterolemia
Extremely rare autosomal recessive
disorder wherein phytosterols (plant
sterols) are absorbed and accumulate in
plasma and peripheral tissues
Results from mutations in the ABCG8 or
ABCG5 gene
DISEASES OF LIPIDS AND LIPOPROTEINS
B. High Triglycerides with Normal Cholesterol
Hyperprebetalipoproteinemia (VLDL, Chylo,
Normal LDL-c)
Defect in LPL, Apo-CII
1. Diabetic Dyslipidemia
2. Familial Hypertriglyceridemia (Type 4
hyperlipidemia)
3. Lipoprotein Lipase Deficiency
(Hyperlipoproteinemia Type 1 or
hyperchylomicronemia)
Defective or absent lipoprotein lipase creates an
inability to clear chylomicrons, creating the classic
type 1 chylomicronemia syndrome
DISEASES OF LIPIDS AND LIPOPROTEINS
4. ApoC-II Deficiency
ApoC-II is an activating cofactor for
LPL. Thus, the absence of apoC-II
creates a functional LPL deficiency
5. ApoC-III Excess
ApoC-III excess interferes with the
activity of lipoprotein lipase and bind to
the carboxy-terminal portion of
apolipoprotein B, preventing the
binding of lipoproteins to the LDL
receptor
DISEASES OF LIPIDS AND LIPOPROTEINS
C. High Cholesterol with High Triglycerides
1. Familial Combined Hyperlipidemia (Type 2B)
2. Acquired Combined Hyperlipidemia
3. Dysbetalipoproteinemia (Type 3)
Mutation leading to lower or loss of affinity of
ApoE to LDL receptors leading to accumulation
of IDL, VLDL and chylomicrons remnants.
Pathognomonic feature: a broad abnormal band
between VLDL and LDL known as abnormally
migrating beta lipoprotein, or -VLDL.
Cholesterol content of VLDL is increased
4. Hepatic Lipase Deficiency
5. Cholesterol 7-Alpha-Hydroxylase Deficiency
DISEASES OF LIPIDS AND LIPOPROTEINS
D. Low Total Cholesterol and Triglyceride
Associated with defective apoB synthesis or metabolism,
leading to low or nonexistent levels of apo-B lipoproteins such
as CM, VLDL, and LDL.
Triglycerides and cholesterol are low.
Fat-soluble vitamin deficiencies are common.
1. Abetalipoproteinemia
also known as Bassen-Kornzweig syndrome
Mutation leading to lack of functional microsomal
triglyceride transport protein (MTP) affecting the synthesis
of ApoB. Both Apo B48 and Apo B100 are absent in
plasma
Present with undetectable plasma apoB containing
lipoproteins
Patients develop fat-soluble vitamin deficiencies caused
by malabsorption of vitamins A, K, and E
Acanthocytes noted on PBS
DISEASES OF LIPIDS AND LIPOPROTEINS

2. Hypobetalipoproteinemia
affects apoB100 and apoB48
3. Chylomicron Retention Disease
affects only apoB-48
DISEASES OF LIPIDS AND LIPOPROTEINS
E. ISOLATED LOW HDL-C
1. Familial Hypoalphalipoproteinemia
2. ApoA-I Deficiency and ApoC-III Deficiency
3. ApoA-I Variants
4. Tangier Disease
A rare autosomal recessive disorder leading to
absence of ABCA1 protein impairing the
transfer cholesterol and phospholipids from
within the cell onto nascent apoA1 proteins in
plasma
Patients have hepatosplenomegaly, peripheral
neuropathy, orange tonsils, and premature
coronary disease
DISEASES OF LIPIDS AND LIPOPROTEINS

5. Lecithin : Cholesterol
Acyltransferase Deficiency
(LCAT)
Without LCAT, most cholesterol
remain unesterified and HDL
synthesis is impeded
DISEASES OF LIPIDS AND LIPOPROTEINS
F. ISOLATED HIGH HDL-C
1. Cholesteryl Ester Transfer
Protein (CETP) Gene Defects
CETP deficiency is an autosomal
recessive disorder in which the
transfer of cholesterol esters from
HDL to apoB-100 rich LPP in
exchange of TAG is inhibited. As a
result, HDL particles are large and
laden with cholesterol ester, and
apoA-I is increased, as is HDL-C
TYPES Particle TAG CHOLE LDL VLDL CHYLO

I. Familial
chylomicronemia or CM
LPL Deficiency
IIa. Familial
LDL
Hypercholesterolemia
IIb. Combined
VLDL
Hyperlipoproteinemia
, LDL
(most common)
IDL,
III.Dysbetalipoproteine
b-
mia
VLDL
IV. Primary
VLDL
hypertriglyceridemia
V. Mixed VLDL
hyperlipidemia ,CM
 THERAPEUTIC MANAGEMENT
Fibric acid derivative and niacin
increases plasma HDL-c
Bile acid sequestrants
(Cholestyramine , Colesevelam ,
Colestipol)
inhibits gut absorption of cholesterol
interferes in the absorption of fat-soluble
vitamins
Statins (Lovastatin, Simvastatin,
Pravastatin, etc.)
blocks intracellular cholesterol synthesis
by inhibiting the enzyme HMG-CoA
reductase
 THERAPEUTIC MANAGEMENT
Ezetimide
inhibits gut absorption of cholesterol by
inhibiting Niemann-Pick C1-Like 1
(NCPL-1) transporter in the intestine
does NOT interfere in the absorption of
fat-soluble vitamins
Fish Oil containing omega-3
(eicosapentaenoic acid,
docosahexaenoic acid)
decrease hepatic TAG synthesis by
inhibiting diaclyglycerol acyltransferase,
fatty acid synthase and acetyl-coA
carboxylase enzymes