CLIN CHEM: LIPIDS & LIPOPROTEINS • The very low-density lipoproteins (VLDL) are like tanker trucks, carrying

triglycerides assembled in the liver to cells for energy needs or storage as

Chapter Outline
fat.
▪ LIPID CHEMISTRY • The low-density lipoproteins (LDL), rich in cholesterol, are the nearly
➢ Fatty Acids empty tankers that deliver cholesterol to peripheral cells and liver after
➢ Triglycerides the triglycerides have been off-loaded.
➢ Phospholipids • The high-density lipoproteins (HDL) are the cleanup crew, gathering up
➢ Cholesterol
excess cholesterol for transport back to the liver.
▪ GENERAL LIPOPROTEIN STRUCTURE
• Cholesterol is used by the body for such useful functions as facilitating
➢ Chylomicrons
triglyceride transport by lipoproteins, for maintaining the normal
➢ Very Low-Density Lipoproteins (VLDL)
➢ Low-Density Lipoproteins (LDL) structure and integrity of cell membranes, and as a precursor for steroid
➢ Lipoprotein (a) hormone synthesis, but when in excess, it can lead to cardiovascular
➢ High-Density Lipoproteins (HDL) disease.
▪ LIPOPROTEIN PHYSIOLOGY AND METABOLISM LIPID CHEMISTRY
➢ Lipid Absorption
➢ Exogenous Pathway • Lipids, commonly referred to as fats, have a dual role.
➢ Endogenous Pathway 1. First, because they are composed of mostly carbon-hydrogen (C-
➢ Reverse Cholesterol Transport Pathway H) bonds, they are a rich source of energy and an efficient way for
▪ LIPID AND LIPOPROTEIN POPULATION DISTRIBUTIONS the body to store excess calories.
▪ DIAGNOSIS AND TREATMENT OF LIPID DISORDERS 2. Second, because of their unique physical properties, lipids are also
➢ Arteriosclerosis an integral part of cell membranes and, therefore, also play an
➢ Hyperlipoproteinemia
important structural role in cells.
➢ Hypercholesterolemia
• The lipids are transported by lipoproteins;
➢ Hypertriglyceridemia
➢ Combined Hyperlipoproteinemia Lipoprotein • Lipids transports triglycerides, phospholipids, cholesterol, and cholesteryl
➢ Elevation Hypolipoproteinemia esters, & these are also the principal lipids found in cells and the main
➢ Hypoalphalipoproteinemia focus of this section

A. Fatty Acids
• Lipoproteins constitute the body’s “petroleum industry.” Like the great oil • Fatty acids, are simply linear chains of CMH bonds that terminate with
tankers that travel the oceans of the world transporting petroleum for fuel a carboxyl group (MCOOH).
needs, chylomicrons are large, lipid- rich transport vessels that ferry • In plasma, only a relatively small amount of fatty acids exists in the
dietary triglycerides, the main oil in the body, throughout the circulatory free or unesterified form, most of which is bound to albumin.
system to cells, finally docking at the liver as chylomicron remnants. • The majority of plasma fatty acids are instead found as a constituent
of triglycerides or phospholipids.
 • Most fatty acids in our diet are of the longchain variety and contain an
even number of carbon atoms.
• Depending on the number of CBC double-bonds, fatty acids can be
classified as being:
(1) saturated (no doublebonds),
(2) monounsaturated (one double-bond), or
(3) polyunsaturated (two or more double-bonds).
• Fatty acid C=C double-bonds can also occur in the trans configuration,
with both hydrogen atoms on opposite side of the C=C double-bond.
The trans fatty acids are not commonly found in nature; however, they
are present in our diet because the chemical hydrogenation treatment
used in food processing for converting polyunsaturated plant oils into
solid margarine introduces trans double bonds.
B. Triglycerides
• As can be inferred from the name, triglycerides contain three fatty
acid molecules attached to one molecule of glycerol by ester bonds.
Each fatty acid in the triglyceride molecule can potentially be
different in structure, thus producing many possible structural forms
of triglycerides.
• Most triglycerides from plant sources, such as corn, sunflower seeds,
and safflower seeds, are rich in polyunsaturated fatty acids and are
oils, whereas triglycerides from animal sources contain mostly
saturated fatty acids and are usually solid at room temperature.
• Triglycerides have no charged groups or polar hydrophilic groups,
making it very hydrophobic and virtually water insoluble. Because it
has no charge, triglyceride is classified as a neutral lipid.
C. Phospholipids
• Phospholipids are similar in structure to triglycerides except that they
only have two esterified fatty acids.
• The various types of phospholipids are named based on the type of
phospholipid head group present.
• Phosphatidylcholine, for example, has a choline head group and is the
most common phospholipid found on lipoproteins and in cell
membranes.
• Because phospholipids contain both hydrophobic fatty acid C=H
chains and a hydrophilic head group, they are by definition
amphipathic lipid molecules and, as such, are found on the surface of
lipid layers.
• The polar hydrophilic head group faces outward toward the aqueous
environment, whereas the fatty acid chains face inward away from
the water in a perpendicular orientation with respect to the lipid
surface.
D. Cholesterol
• Cholesterol is an unsaturated steroid alcohol containing four rings (A,
B, C, and D), and it has a single C=H side chain tail similar to a fatty
acid in its physical properties.
• The only hydrophilic part of cholesterol is the hydroxyl group in the
A-ring. Cholesterol is, therefore, also an amphipathic lipid and is
found on the surface of lipid layers along with phospholipids.
• Cholesterol can also exist in an esterified form called cholesteryl
ester, with the hydroxyl group conjugated by an ester bond to a fatty
acid, in the same way as in triglycerides.
• In contrast to free cholesterol, there are no polar groups on
cholesteryl esters, making them very hydrophobic. Because it is not
charged, cholesteryl esters are classified as a neutral lipid and are not
found on the surface of lipid layers but instead are located in the
center of lipid drops and lipoproteins, along with triglycerides.
• Cholesterol is almost exclusively synthesized by animals, but plants
do contain other sterols similar in structure to cholesterol.
Cholesterol is also unique in that, unlike other lipids, it is not readily
catabolized by most cells and, therefore, does not serve as a source
of fuel.
• Functions of Cholesterol:
 1. Cholesterol can, however, be converted in the liver to • Apolipoproteins are primarily located on the surface of lipoprotein
primary bile acids, such as cholic acid and chenodeoxycholic particles (Table 14-2). They help maintain the structural integrity of
acid, which promote fat absorption in the intestine by acting lipoproteins and also serve as ligands for cell receptors and as
as detergents. activators and inhibitors of the various enzymes that modify
2. A small amount of cholesterol can also be converted by some lipoprotein particles (Table 14-2).
tissue, such as the adrenal gland, testis, and ovary, to steroid
hormones, such as glucocorticoids, mineralocorticoids, and
estrogens.
3. Finally, a small amount of cholesterol, after first being
converted to 7- dehydrocholesterol, can also be transformed
to vitamin D3 in the skin by irradiation from sunlight.

GENERAL LIPOPROTEIN STRUCTURE

• Because the main role of lipoproteins is the delivery of fuel to

peripheral cells, the core of the lipoprotein particle essentially
represents the cargo that is being transported by lipoproteins. The
size of the lipoprotein particle correlates with its lipid content.
• The larger lipoprotein particles have correspondingly larger core
regions and, therefore, contain relatively more triglyceride and
cholesteryl ester. The larger lipoprotein particles also contain more
lipid relative to protein and thus are lighter in density.
• The various lipoprotein particles were originally separated by
ultracentrifugation into different density fractions (chylomicrons
[chylos], VLDL, LDL, and HDL), which still form the basis for the most
commonly used lipoprotein classification system.

Apolipoproteins

• Apolipoproteins are amphipathic molecules capable of interacting

with both the lipids of the lipoprotein core and the aqueous
environment of the plasma.
• They function as biochemical keys, allowing lipoprotein particles
access to specific sites for the delivery, acceptance, or modification
of lipids.
Classification of Lipoproteins
Based on Electrophoretic Mobilities
• Lipoproteins may be separated according to their
electrophoretic properties into: α, pre-β, β, and broad beta
lipoproteins.
• The mobility of a lipoprotein is mainly dependent upon
protein content.
• Those with higher protein content will move faster towards
the anode and those with minimum protein content will
have minimum mobility.
Based on nature of Apo-protein content
• One or more apolipoproteins (proteins or polypeptides) are
present in each lipoprotein.
• The major apolipoproteins of HDL (α-lipoprotein) are
designated A.
• The main apolipoprotein of LDL (β-lipoprotein) is
apolipoprotein B (B-100), which is found also in VLDL.
• Chylomicrons contain a truncated form of apo B (B-48) that
is synthesized in the intestine, while B-100 is synthesized in
the liver.
• Apo E is found in VLDL, HDL, Chylomicrons, and chlomicron
remnants.
A. Chylomicrons
• Chylomicrons, which contain apo B-48, are the largest and the least
dense of the lipoprotein particles, having diameters as large as 1200
nm13.
• Because of their large size, they reflect light and account for the
turbidity of postprandial plasma.
• Because they are so light, they also readily float to the top of stored
plasma and form a creamy layer, which is a hallmark for the presence
of chylomicrons.
• Chylomicrons are produced by the intestine, where they are
packaged with absorbed dietary lipids.
• Once they enter the circulation, triglycerides and cholesteryl esters
in chylomicrons are rapidly hydrolyzed by lipases and, within a few
hours, they are transformed into chylomicron remnant particles,
which are recognized by proteoglycans and remnant receptors in the
liver, facilitating their uptake.
• The principal role of chylomicrons is the delivery of dietary lipids to
hepatic and peripheral cells.
 B. Very Low Density Lipoproteins
• VLDL is produced by the liver and contains apo B-100, apo E, and
apo Cs;
• like chylomicrons, they are also rich in triglycerides.
• They are the major carriers of endogenous (hepatic-derived)
triglycerides and transfer triglycerides from the liver to peripheral
tissue.
• Like chylomicrons, they also reflect light and account for most of
the turbidity observed in fasting hyperlipidemic plasma
specimens, although they do not form a creamy top layer like
chylomicrons, because they are smaller and less buoyant.
• Excess dietary intake of carbohydrate, saturated fatty acids, and
trans fatty acids enhances the hepatic synthesis of triglycerides,
which in turn increases VLDL production.
C. Low-Density Lipoproteins
• LDL primarily contains apo B-100 and is more cholesterol rich than
other apo B–containing lipoproteins.
• They form as a consequence of the lipolysis of VLDL.
• LDL is readily taken up by cells via the LDL receptor in the liver and
peripheral cells.
• In addition, because LDL particles are significantly smaller than
VLDL particles and chylomicrons, they can infiltrate into the
extracellular space of the vessel wall, where they can be oxidized
and taken up by macrophages through various scavenger
receptors.
• Macrophages that take up too much lipid become filled with
intracellular lipid drops and turn into foam cells, which is the
predominant cell type of fatty streaks, an early precursor of
atherosclerotic plaques.
• LDL particles can exist in various sizes and compositions and have
been separated into as many as eight subclasses through density
ultracentrifugation or gradient gel electrophoresis.
• The LDL subclasses differ largely in their content of core lipids;
• the smaller particles are denser and have relatively more
triglyceride than cholesteryl esters.
• Recently, there has been great interest in measuring LDL
subfractions, because small, dense, LDL particles have been
shown to be more proatherogenic and may be a better marker for
coronary heart disease risk.
D. Lipoprotein(a)
• Lipoprotein(a) particles are LDL-like particles that contain one
molecule of apo (a) linked to apo B-100 by a disulfide bond.
• Lp(a) particles are heterogeneous in both size and density, as a
result of a differing number of repeating peptide sequences, called
kringles, in the apo (a) portion of the molecule.
• The concentration of Lp(a) is inversely related to the size of the
isoform.
• Plasma levels of Lp(a) vary widely among individuals in a population
but remain relatively constant within an individual.
• Elevated levels of Lp(a) are thought to confer increased risk for
premature coronary heart disease and stroke.
• Because the kringle domains of Lp(a) have a high level of homology
with plasminogen, a protein that promotes clot lysis, it has been
proposed that Lp(a) may compete with plasminogen for binding
sites, thereby promoting clotting, a key contributor to both
myocardial infarction and stroke.
E. High-Density Lipoproteins
• HDL, the smallest and most dense lipoprotein particle, is
synthesized by both the liver and intestine.
• HDL can exist as either disk-shaped particles or, more commonly,
spherical particles.
• Discoidal HDL typically contains two molecules of apo A-I, which
form a ring around a central lipid bilayer of phospholipid and
cholesterol.
 • Discoidal HDL is believed to represent nascent or newly secreted HDL
and is the most active form in removing excess cholesterol from
peripheral cells.
• The ability of HDL to remove cholesterol from cells, called reverse
cholesterol transport, is one of the main mechanisms proposed to
explain the antiatherogenic property of HDL.
• When discoidal HDL has acquired additional lipid, cholesteryl esters
and triglycerides form a core region between its phospholipid bilayer,
which transforms discoidal HDL into spherical HDL.
• HDL is highly heterogeneous separable into as many as 13 or 14
different subfractions.
• There are two major types of spherical HDL based on density
differences: HDL2 and HDL3.
• HDL2 particles are larger in size and richer in lipid than HDL3 and may
reflect better efficiency in delivering lipids to the liver.
LIPOPROTEIN PHYSIOLOGY AND METABOLISM
• The lipid absorption pathway, the exogenous pathway, and the
endogenous pathway, which all depend on apo B–containing
lipoprotein particles, can be viewed as means to transport dietary
lipid and hepatic-derived lipid to peripheral cells.
• In terms of energy metabolism, these three pathways are critical in
the transport to peripheral cells of fatty acids, which are generated
during the lipolysis of triglycerides and, to a lesser degree, cholesteryl
esters on lipoproteins.
• Peripheral cells are prone to accumulating cholesterol because they
also (1) synthesize their own cholesterol, and, unlike liver cells, they
(2) do not have the enzymatic pathways to catabolize cholesterol.
• Furthermore, cholesterol is (3) relatively water insoluble and cannot
readily diffuse away from its site of deposition or synthesis.
• One principal way that peripheral cells maintain their cholesterol
equilibrium is the reverse cholesterol transport pathway (Fig. 14-3),
which is mediated by HDL.
• In this pathway, excess cholesterol from peripheral cells is
transported back to the liver, where it can be excreted into the bile
as free cholesterol or after being converted to bile acids.
• The liver is, therefore, involved in both forward and reverse
cholesterol transport pathways and, in many ways, acts as a buffer in
helping the body maintain its overall cholesterol level.
A. Lipid Absorption
• Because fats are water insoluble, special mechanisms are required to
facilitate the intestinal absorption of the 60 to 130 g of fat per day in
a typical Western diet.
• During the process of digestion, pancreatic lipase, by cleaving off
fatty acids, first converts dietary lipids into more polar compounds
with amphipathic properties.
• Thus,
➢ **triglycerides are transformed into monoglycerides and
diglycerides;
➢ **cholesterol esters are transformed into free
cholesterol;
➢ **and phospholipids are transformed into
lysophospholipids.
• These amphipathic lipids in the intestinal lumen form large
aggregates with bile acids called micelles. Lipid absorption occurs
when the micelles come in contact with the microvillus membranes
of the intestinal mucosal cells. Triglyceride absorption is efficient:
➢ ***greater than 90% of dietary triglycerides are taken up
by the intestine.
• In contrast, only about half of the 500 mg of cholesterol in the
typical diet is absorbed each day. Even a smaller fraction of plant
sterols are absorbed by the intestine.

B. Exogenous Pathway
• The newly synthesized chylomicrons in the intestine (Fig. 14-3) are
initially secreted into the lymphatic ducts and eventually enter the
circulation by way of the thoracic duct.
• After entering the circulation, chylomicrons interact with
proteoglycans, such as heparan sulfate, on the surface of
capillaries in various tissues, such as skeletal muscle, heart, and
adipose tissue.
• The proteoglycans on capillaries also promote the binding of
lipoprotein lipase (LPL), which hydrolyzes triglycerides on
chylomicrons.
• The free fatty acids and glycerol generated by the hydrolysis of
triglycerides by LPL can then be taken up by cells and used as a
source of energy.
• Excess fatty acids, particularly in fat cells (adipocytes), are re-
esterified into triglycerides for long term storage in intracellular
lipid drops.
• During lipolysis of chylomicrons, there is a transfer of lipid and
apolipoproteins onto HDL, and chlyomicrons are converted within
a few hours after a meal into chylomicron remnant particles.
• Chylomicron remnants are rapidly taken up by the liver through
interaction of apo E with specific remnant receptors on the
surface of liver cells.
• Once in the liver, lysosomal enzymes break down the remnant
particles to release free fatty acids, free cholesterol, and amino
acids. Some cholesterol is converted to bile acids.
• Both bile acids and free cholesterol are directly excreted into the
bile but not all of the excreted cholesterol and bile salt exit the
body.
• As previously described, approximately half of the excreted biliary
cholesterol is reabsorbed by the intestine, with the remainder
appearing in the stool, as fecal neutral steroids.
• In the case of bile acids, almost all of the bile acids are reabsorbed
and reused by the liver for bile production.
C. Endogenous Pathway
• Most triglycerides in the liver that are packaged into VLDL are derived
from the diet after recirculation from adipose tissue.
• Only a small fraction is synthesized de novo in the liver from dietary
carbohydrate.
• VLDL particles, once secreted into the circulation, undergo a lipolytic
process similar to that of chylomicrons (Fig. 14- 3).
• VLDL loses core lipids causing dissociation and transfer of
apolipoproteins and phospholipids to other lipoprotein particles,
primarily by the action of LPL.
• During this process, VLDL is converted to VLDL remnants, which can
be further transformed by lipolysis into LDL.
• About half of VLDL is eventually completely converted to LDL, and the
remainder is taken up as VLDL remnants by the liver remnant
receptors.
• LDL particles are the major lipoproteins responsible for the delivery
of exogenous cholesterol to peripheral cells due to the efficient
uptake of LDL by the LDL receptors.
• Once bound to LDL receptors, they are endocytosed by cells and
transported to the lysosome, where they are degraded.
• The triglycerides in LDL are converted by acid lipase into free fatty
acids and glycerol and further metabolized by the cell for energy or
are reesterified and stored in lipid drops for later use.
• Free cholesterol derived from degraded LDL can be used for
membrane biosynthesis, and excess cholesterol is converted by acyl-
CoA:cholesterol acyltransferase (ACAT) into cholesteryl esters and
stored in intracellular lipid drops.
• The regulation of cellular cholesterol biosynthesis is, in part,
coordinated by the availability of cholesterol delivered by the LDL
receptor.
• Many enzymes in the cholesterol biosynthetic pathway (e.g., HMG-
CoA reductase, the main target for the cholesterol-lowering statin-
 type drugs) are downregulated, along with the LDL receptor, when • (2) Another pathway in which HDL mediates the removal of
there is excess cellular cholesterol by a complex mechanism involving cholesterol from cells, involves the ABCA1 transporter.
both gene regulation and post-transcriptional gene regulation. • The ABCA1 transporter is a member of the ATP-binding cassette
• Abnormalities in LDL receptor function result in elevation of LDL in transporter family that pumps various ligands across the plasma
the circulation and lead to hypercholesterolemia and premature membrane.
atherosclerosis. • Defects in the gene for the ABCA1 transporter lead to Tangier
disease, a disorder associated with low HDL and a predisposition to
D. Reverse Cholesterol Transport Pathway premature coronary heart disease.
• As previously described, one of the major roles of HDL is to
maintain the equilibrium of cholesterol in peripheral cells by the
reverse cholesterol transport pathway (Fig. 14-3).
• HDL is believed to remove excess cholesterol from cells by
multiple pathways.
• (1) In the aqueous diffusion pathway, HDL acts as a sink for the
small amount of cholesterol that can diffuse away from the cells.
Although cholesterol is relatively water insoluble, because it is
an amphipathic lipid, it is soluble in plasma in micromolar
amounts and can spontaneously dissociate from the surface of
cell membranes and enter the extracellular fluid. Some free
cholesterol will then bind to HDL in the extracellular space, and,
once bound, it becomes trapped in lipoproteins after it is
converted to cholesteryl ester by lecithin: cholesterol
acyltransferase (LCAT), which resides on HDL. HDL can then
directly deliver cholesterol to the liver by the SR-BI receptor and,
possibly, other receptors.
• Approximately half of the cholesterol on HDL is returned to the
liver by the LDL receptor, after first being transferred from HDL
to LDL by the cholesteryl ester transfer protein (CETP), which
connects the forward and reverse cholesterol transport
pathways (Fig. 14-3). Cholesterol that reaches the liver is then
directly excreted into the bile or first converted to a bile acid
before excretion.

LIPID AND LIPOPROTEIN POPULATION DISTRIBUTIONS
• Serum lipoprotein concentrations differ between adult men and
women, primarily as a result of differences in sex hormone levels,
DIAGNOSIS AND TREATMENT OF LIPID DISORDERS
with women having, on average, higher HDL cholesterol levels and
lower total cholesterol and triglyceride levels than men.
• The difference in total cholesterol, however, disappears after
menopause as estrogen decreases.  Men and women both show a
tendency toward increased total cholesterol, LDL cholesterol, and
triglyceride concentrations with age.
• HDL cholesterol concentrations generally remain stable after the
onset of puberty and do not drop in women with the onset of
menopause.
• General adult reference ranges are shown in Table 14-3.
• The incidence of heart disease is strongly associated with serum
cholesterol concentration.
• Comparisons across different societies show that eating less animal
fat and more grains, fruits, and vegetables, as is common in many
Asian populations, is associated with lower LDL cholesterol and lower
rates of heart disease compared with societies that ingest more fat,
particularly animal fat, and are more sedentary.
• These differences can be attributed to both genetic and lifestyle
factors in the various countries and ethnic groups.
• The importance of diet was clearly shown in a study that compared
the dietary patterns and heart disease rates in Japanese men living in
Japan, Hawaii, and California. In this study, as dietary intake became
more westernized, with increased consumption of fat and
cholesterol, the LDL cholesterol concentrations increased, as did the
rates of heart disease, Japanese men living in California were found
to have much higher rates of heart disease than Japanese men living
in Japan;
• Diseases associated with abnormal lipid concentrations are referred
to as dyslipidemias.
• They can be caused directly by genetic abnormalities or through
environmental/lifestyle imbalances, or they can develop secondarily,
as a consequence of other diseases.
• Dyslipidemias are generally defined by the clinical characteristics of
patients and the results of laboratory tests and are not necessarily
defined by the specific genetic defect associated with the
abnormality. Many, but not all, dyslipidemias, regardless of etiology,
are associated with CHD, or arteriosclerosis.
• Arteriosclerosis In the United States and many other developed
countries, arteriosclerosis is the single leading cause of death and
disability. The mortality rate has decreased in the United States in the
past few years, partly as a result of advances in diagnosis and
treatment but also because of changes in lifestyle in the American
population. This increased awareness of the importance of diet and
exercise in preventing CHD has resulted in an overall decrease in the
average serum cholesterol concentration and in a lower prevalence
of heart disease.
• Fatty streaks can develop over time into plaques that contain
increased number of smooth muscle cells, extracellular lipid,
calcification, and fibrous tissue, which can partially block or occlude
blood flow.
• Because lipid deposits in the vessel walls are frequently associated
with increased serum concentrations of LDL cholesterol or decreased
HDL cholesterol, lowering LDL is an important step in preventing and
treating CHD.
Dyslipidemias can be subdivided into two major categories:
• Hyperlipoproteinemias, which are diseases associated with
elevated lipoprotein levels . The hyperlipoproteinemias are
subdivided into ;
1. hypercholesterolemia
2. Hypertriglyceridemia
3. combined hyperlipidemia with elevations of both
cholesterol and triglycerides.
• Hypolipoproteinemias, which are associated with decreased
lipoprotein levels.
Hypercholesterolemia
• Hypercholesterolemia is the lipid abnormality most closely linked to
heart disease.
• Familial hypercholesterolemia (FH) – is one form of the
disease, which is associated with genetic abnormalities that
Combined Hyperlipoproteinemia
predispose affected individuals to elevated cholesterol
levels. Other symptoms associated with FH include
tendinous and tuberous xanthomas, which are cholesterol
deposits under the skin, and arcus, which are cholesterol
deposits in the cornea
➢ Homozygotes for FH are fortunately rare (1:1 million in the
Lipoprotein(a) Elevation
population) and can have total cholesterol concentrations
as high as 800 to 1,000 mg/dL (20–26 mmol/L). These
patients frequently have their first heart attack when still in
their teenage years.
Hypolipoproteinemia
➢ Heterozygotes for the disease are seen much more
frequently (1:500 in the population) because it is an
autosomal codominant disorder. They have total
cholesterol concentrations in the range of 300–600 mg/dL
(8–15 mmol/L) and, if not treated, become symptomatic for
heart disease in their 20s to 50s.
Hypertriglyceridemia
• The NCEP ATP has identified borderline high triglycerides as levels of
150–200 mg/dL (1.7–2.3 mmol/L), high as 200–500 mg/dL (2.3–5.6
mmol/L), and very high as greater than 500 mg/dL ( 5.6 mmol/L).
• Hypertriglyceridemia can be a consequence of genetic abnormalities,
called familial hypertriglyceridemia, or the result of secondary
causes, such as hormonal abnormalities associated with the
pancreas, adrenal glands, and pituitary, or of diabetes mellitus or
nephrosis.
• Hypertriglyceridemia is generally a result of an imbalance between
synthesis and clearance of VLDL in the circulation
• Treatment of hypertriglyceridemia consists of dietary modifications,
fish oil, and or triglyceride-lowering drugs (primarily, fibric acid
derivatives) in cases of severe hypertriglyceridemia or when
accompanied with low HDL cholesterol.
• Combined hyperlipoproteinemia is generally defined as the presence
of elevated levels of serum total cholesterol and triglycerides.
Individuals presenting with this syndrome are considered at
increased risk for CHD.
• Elevations in the serum concentration of Lp(a), especially in
conjunction with elevations of LDL, increase the risk of CHD and CVD.
• Hypolipoproteinemias, or low levels of lipoproteins, exist in two
forms: hypoalphalipoproteinemia and hypobetalipoproteinemia.
• Hypoalphalipoproteinemia - indicates an isolated decrease in
circulating HDL, currently defined by the NCEP as an HDL cholesterol
concentration less than 40 mg/dL (1.0 mmol/L), without the presence
of hypertriglyceridemia.
Side Notes (Youtube Video) Structure

LIPOPROTEIN

• Group of proteins synthesized in small intestine and liver.

• Transports hydrophobic lipids such as cholesterol, triglycerides, and
phospholipids throughout the body.
• Based on the density of their contents:
✓ Chylomicron
✓ Chylomicron remnant
✓ VLDL
✓ VLDL Remnant/ IDL
✓ LDL
✓ HDL • Core: Hydrophobic Lipids (Cholesterol esters, Triglyceride)
• Shell: Hydrophilic lipid components (free Cholesterol, Phospholipids)
and Hydrophilic proteins, so called Apolipoproteins.

Basics of Lipid Transport

• Lipids are non-polar substances (insoluble in water)

• Transport medium in our body is Blood, which is polar.
• Lipids are insoluble in a polar medium, so they cannot be transported
directly or alone.
• Lipoproteins play a crucial role in transportation of lipids by making
them polar (soluble in water) with a lipid and protein combination.
• The lipid polar portion which is non polar is placed in the core, and
Note: the protein portion which is polar is placed in the periphery, so that
lipoprotein can easily travel in the blood and helps the transportation
➢ Chylomicrons are the least dense
of lipids in one place to another.
➢ HDL is the most dense
CHYLOMICRONS
• Lipids Present in Lipoproteins:
- A lipoprotein that carries lipids and cholesterol from the small
✓ Triglycerides
intestine to adipocytes, cardiac muscle, and skeletal muscle.
✓ Phospholipids
- Composed of outer phospholipids with embedded Apo-lipoproteins
✓ Free Cholesterol (Unesterifified)
and a core containing lipids and cholesterol.
✓ Cholesterol-ester
- Very large particles
 - Composition: Triglycerides more than Cholesterol. (TAG > CHO) LOW DENSITY LIPOPROTEIN (LDL)
- Secreted by the intestinal epithelial cells in to the Lymphatics.
- Bad Cholesterol
- Functions:
- Composition: Cholesterol more than Triglycerides (TAG < CHO)
▪ Transport dietary triglycerides from the intestine to the
- Formed from the IDL, secondary to hepatic lipase with modification
peripheral tissues.
in peripheral tissue and the liver.
▪ Transport cholesterol to the liver in the form of chylomicron
- Endocytosis by target cells with LDL receptors and degraded,
remnants.
releasing cholesterol which decreases further uptake of cholesterol.
- Chylomicron remnants – chylomicrons that are depleted of
- Functions:
triglycerides.
▪ Transports cholesterol from the liver to peripheral tissues.
- Apo-lipoproteins associated with chylomicrons:
- Apo-lipoproteins associated with IDL:
✓ ApoE
✓ B-100
✓ ApoC-II = activates capillary lipoprotein lipase
✓ ApoB-48 HIGH DENSITY LIPOPROTEIN (HDL)
VERY LOW DENSITY LIPOPROTEIN (VLDL)
- Good cholesterol
- Lipoprotein secreted by the liver.
- The higher the concentration, the lower the risk to coronary heart
- Composition: Triglycerides more than Cholesterol (TAG > CHO)
disease.
- Functions:
- Composition: Cholesterol more than Triglycerides (TAG < CHO)
▪ Transports triglycerides from the liver to peripheral tissues
- Secreted by intestinal epithelial and Liver
- Converted by LDL by hydrolysis of fatty acids by capillary lipoprotein
- Functions:
lipase.
▪ Transports cholesterol from peripheral tissues
- Apo-lipoproteins associated with VLDL:
(artherosclerotic arteries) to the liver (reverse cholesterol
✓ ApoE
transport), where it is excreted via bile.
✓ ApoC-II
- Apo-lipoproteins associated with HDL:
✓ B-100
✓ ApoE
INTERMEDIATE-DENSITY LIPOPROTEIN (IDL) ✓ ApoA-1 (Activates LCAT to form cholesteryl esters)
- Composition: Cholesterol and Triglycerides (CHO = TAG) ✓ ApoC-II
- Degradation of VLDL forms IDL
APOLIPOPROTEINS
- Function:
▪ Transports triglycerides and cholesterol to the liver from - Proteins present in the lipoprotein.
peripheral tissues. - Its synthesis occurs at the Rough Endoplasmic Reticulum and Golgi
- Apo-lipoproteins associated with IDL: Apparatus.
✓ ApoE
✓ B-100
Apolipoprotein A-I (apoA-I)

• Activates lecithin cholesterol acyltransferase (LCAT), esterifies tissue

cholesterol picked up by HDL.
• Major structural protein for HDL

Apolipoprotein A-II (apoA-II)

Apolipoprotein B-48 (apoB-48)

• Component of chylomicrons

Apolipoprotein B-100 (apoB-100)

• Contains the B-48 domain plus the LDL receptor recognition domain.
• Only structural protein in LDL
-END-
Apolipoprotein C-I (apoC-I)

Apolipoprotein C-II (apoC-II)

Friendly reminder!
• Activates capillary lipoprotein lipase, releases fatty acids and glycerol
from chylomicrons, VLDL, and IDL.

Apolipoprotein E (apoE)

• Mediate up take of chylomicron remnants and intermediate-density

lipoprotein (IDL) by the liver.

Density of Lipoproteins

• Density is directly proportional to the percentage of proteins

• Density is inversely proportional to triglyceride contents and size

Prepared by:

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