1. Fredri ckson classification of Hyperlfpidemias
Hyperlip oprot eine mia Increased Serum
OMIM B, Synony ms B D ef ect 8 Treatm ent B
OJ lipoprotein 8 appe arance B
Buerger-Gruelz syndrome , Prim8ry ~ecreaS~dr
Ipoprotem Ipase
Type I (rare) 238600 t§! hyperllpoprotem8eml8 , or F8mlli81 Chy1omlcrons Diet control Creamy lop layer
(LPL) or altered
hyperchylomicronem l8
ApoC2
Bile aCid
144400 t§! Polygenic hypercholeslerol8emi8 LDL receptor
Type lIa LDL sequestrants. Clear
or F8mlli8! hypercholestero!eml8 deficiency
statlns. niacin
Decreased LDL
Statins. niacin,
Ty pe lib 144400 t§! Combined hyperlipidemi8 receptor and LDL and VLDL Clear
fib rate
increased ApoB
Type III (rare) 110774 1 19 F8mi!i81dysbelallpoproteinemia
I~efect in Apo E 2 IDL Fibrates. statins Turbid
synthesIs I
Increased VLDL I
production and Flbrate, niacin],
Ty pe IV 144600 19 Familial hyperlipemia VLDL Turbi d
Decreased statins
eliminati on
Increased VLDL
VLDL and Creamy top layer
Type V (rare) 1 44650 ~ Endogenous hyperlng /ycendemia production and Niacin. fibrate
Chy1omlcrons & turbid bottom
, , , Decreased LPL , , ,
T y pes of H y perlipidemia :
Accordin e rickso n C lassification there are f ive t y pes of h y perlipidae
- Ra ised cholesterol w ith h ig h trigly ceride levels .
II - High cho lesterol w ith normal t rigl y ceride le v els.
T y pe III - Raised cholesterol and trigl y cerides.
T y pe IV - Ra ised trigly cerides , atheroma . raised uric acid .
y pe V - Ra is ed trig lycerid es .
All are a,~s 5o3t~'''''''~:::!.! h~
~s i W it! s:ymptoms of x anthoma and he pato~Pleeno m e~a
~~ !!ll""_--~
1. Type I - The symptoms are Buerger-Gruetz syndrome, Primary hyperiipoproteinaemia, or Fam ilial hyperchylomicronemia. The
treatment for this is Diet Control.
2. Type lIa - The symptoms are Polygenic hypercholesterolaemia or Familial hypercholesterolemia. The treatment for this is Diet,
Statins , Bile Acid Sequestrants, Nicotinic Acid.
3. Type lib - The symptom is Combined hyperlipidemia. The treatment for this is Diet, Stat ins, Bile Acid Sequestrants , Fibrates ,
Nicotinic Acid.
4. Type III - The symptom is Fam ilial dysbeta lipoproteinemia. The treatment for this is Diet, Fibrates, Nicotinic Acid.
5. Type IV - The symptom is Famil ial hy perlipemia. The treatment for th is is Diet, Fibrates , Nicotinic Acid.
6. Type V - The symptom is Endogenous hy pertriglyceridemia. The treatment for this is Diet, Fibrates , Nicotinic Ac id.

2. lipo protein lipase (Ee 3.1.1.34) is an
enzyme that hydrolyzes ~pids in
lipoproleins, such as those found in
chylomicrons and very Iow~ density
lipoproteins (VlDl), into two free fatty
acids and one monoacylglycerol molecule.
It requires Apo -CU as a cofactor. (1)
Lipoprotein lipase is specifically found in
endothelial cells lining the capillaries.
Regulati on
Insulin is known to induce lPl synthesis in
LPL encodes lipoprotein lipase, which is
adlpocytes and its placem ent in the
expressed in heart, muscle, and adipose
capillary endothelium.
tissue. LPl functions as a homodimer, and
has the dual functJoos of triglyceride lPL has different lsozymes in different
hydrolase and ligandfbridging factor for tissues. The form that is in adipocytes is
receptor-mediated Hpoprotein uptake. activated by insulin, whereas that in
Severe mutations that cause LPL muscle and myocardium is not. This helps
deficiency result in type I to explain why adipose cels gain fat in a
hyperlipoproteinemia, while less extreme well -led state.
mutations in LPL are linked to many
01lipoprotein metabolism.l2J
disorders
- ..
Patho logy
Lipoprotein lipase defICIency leads to hypertriglyceridemia (elevated levels of
triglycerides in the bIood slream ).(3)
Diets high in refined carbohydrates have been shown to cause tissue- specific
overexpression of LPL: This has been implicated in tissue-specific insulin resistance and
consequent development of type 2 diabetes melillus.
A polipo protein B (APOB) is the Through a mechanism that is not fully
primary apolipoprotein of low-density understood, high levels of APOB can
lipoproteins (l O l or "bad choIesterol"), lead to plaques that cause vascular
which is responsible for cafTYing disease ( atherosclerosis), leading to
chotesterol to tissues. While it is
heart disease. There is considerable
undear exactly what functionat role
evidence that levels of APO S are a
APOB plays in lOl , it is the primary
beller indicator of heart disease risk
apotipoprotein component and is
absolutely required for its fOfTllatJoo. than total cholesterol or LDL However ,
What is d eal" is that the APOB on the primarily for practical reasons ,
lOl partid e acts as a tigand for lOl cholesterol, and more specifically, LDl-
receptors in various celts throughout cholesterol, remains the primary lipid
the body (i.e. less formatly, APOB
target and risk factor for
"unlocks" the doors to celts and
atherosclerosis.
thereby delivers chotesterol to them).

3. The Low-Density Lipoprotein
(LOL) Receptor is a mosaic protein
that mediates the endocytosis of
cholesterol-rich LDL It is a cell -
surface receptor that recognizes the
apoprotein 8100 which is embedded
in the phospholipid outer layer of
Apolipoprotein C2 lDl particles. The receptor also
view original wikipedia article recognizes the apoE protein found in
chylomicron remnants and VLDL
Apolipoprotein C2 is an apolipoprotein
remnants (IOL). Brown and
responsible for the activation of lipoprotein
Goldstein won a Nobel Prize for their
lipase (LPL) in capillari es l 1) and thus klentification of the Low Density
begins the catabolism of the chyloITlIcrons Lipoprotein (LOL) receptor in 1985
and VLDl. It is also found in HDL. Deficits whilst they were studying familial
of this apoprolein C2 present with grave hypercholesterolemia .
hypertrigtyceridemia and
hyperchylomicronemia during fasting It belongs to the Low density
lipoprotein receptor gene family.
Cholt!St~rol is a way;y steroid metabolite found
Apolipoprot@in E (APOE) is a dass of in the cell membranes and transported in the
apolipoprotein found in the chylomicron
blood plasma of all animals.[211t is an essential
and IDLs that binds to a specific
structural component of mammalian cell
receptor on liver cells and peripheral
membranes, where it is required to establish
cells. It is essential for the normal
proper membrane permeability and fluidity. In
catabolism of triglyceride-rich
addition, cholesterol is an important component
lipoprotein constituentsJ1] for the manufacture of bile ackls , steroid
hormones, and several fat-soluble vitamins.
Cholesterol depletion is when cholesterol levels in the body have been artificially
lowered 100 fur. Natural low cholesterol levels and associated clinical symptoms are
defined as the hypocholesterolemia . Medically induced hypocholes terolemia is
increasingly associated in the elderty w ith long - term statin use. The inhibition of de
novo cholesterol is associated with functional failure of cholesterol -rich lip id rafts in
processes such as exocytOSls and endocytosis .
Chylomicrons are large lipoprotein
particles that transport d ietary lipids
from the intestines to other locations in
the body. Chylomicrons are one of the
five major groups o f lipoproteins
Function
(chylomicrons, V LDL, IDL , LDL, HDL ) C hylomicrons transport exogenous
that enable fats and cholesterol to lipids to liver, adipose , cardiac, and
move within the water- based solution s keletal muscle tissue, where their
o f the bloodstream. triglyceride components are unloaded
by the activity of lipoprotein lipase_ As a consequence, chylomicron remnants are left
over and are taken up by the liver.

4. There are three stages in the chylomicroo's "life cycle":
" Nascent chylomicron
• Mature chylomicron
• Chylomicron remnant
Low-density lipoprolein (lOl) is a type of lipoprotein that transports cholesterol and
triglyceOOes from the liver to peripheral tissues. lOl is one of the live major groups of
lipoproteins; these groops include chylomicrons, very low -density lipoprotein (VlOl),
intermediate -density lipoprotein (IOl), low-density lipoprotein, and high -density
lipoprotein (HOl), although some alternative organizational schemes have been
proposed. like all lipoproteins, lOl en ables fats and cholesterol to move within the
water-based solution of the blood stream. lOl also regulates cholesterol synthesis at
these sites. It is used medically as part of a cholesterol blood test, and since high levels
oflOl cholesterol can signal medical problems like cardiovascular disease, it is
sometimes called "bad cholesterol," (as opposed 0 HOl, which is frequently referred
to as "good cholesterol" or "healthy cholesterol"l.ll)
Transport into the cell
When a cell requires cholesterol , it synthesizes the necessary lOl receptors , and
inserts them into the plasma membrane. The lOl receptors diffuse freely until they
associate with clathrin-coated pits lOL particles in the blood stream bind to these
extracellular lOl receptors The clathrin-coated pits then form vesicles that are
endocytosed into the cell.
Alter the clal hrin coat is shed , the vesicles deliver the lOl and their receptors to earty
endosomes, onto late endosomes to Iysosomes. Here the cholesterol esters in the lOl
are hydrolysed. The LOl receptors are recycled back to the plasma membrane.

6. The lipid profile does not measure LDL level directly but instead estimates it using the
Friedewakl equation [4)[15) using levels of other cholesterol such as HDL:
LDL-C : : : : Total cholesterol- HDL-C - 0.20 * Total triglycendes
In mgldl: LDL cholesterol = tolal cholesterol - HDL cholesterol _ (0.20 x
lriglycerides )
In mmolll: LDL choleslerol = total cholesterol - HDL cholesterol _ (0.45 x
lriglycerides)
There are limitations to this melhod. most notably thaI samples must be obtained after a
12 to 14 h fast and thaI LDL-C cannot be calculated if plasma triglyceride is >4 .52
mmollL (400 mgldL). Even at LDL-C levels 2.5 1 4 .5 mmoUL, this foonula is
0
considered 10 be inacClJrale.[I6] If both total cholesterol and lriglyceride levels are
elevated then a modified formula may be used
In mgldl: LDL-C = Total -C - HDL -C _ (0.16 x Trig )
This foonula provides an approximation with fair accuracy for most people , assuming
the bkxxl was drawn after fasting for about 14 hours or longer. (However. the
concentration of LDL particles, and to a lesser extenl their size, has far tighter
correlation with c~nical oulcome than the content of cholesterol with the LDl particles ,
even if the LDL-C estimation is about correct)

7. Normal ranges
In the USA, the American Heart Association, NIH, and NCEP provide a set of guidelines
for fasting LDL-Cholesterol levels, estimated or measured, and risk for heart disease.
As of 2003, thes.e guidelines were: [t7l1 18](19)
Level Level
Interpret~tion
mgl dL mmoll L
<1 00 <2.6 Optimal LOL cholesterol , corresponding to reduced , but not
zero, risk for heart disease
100 to 2 .6 to 3.3 Near optimal LDL level
129
130 to 3.3t0 4.1 Borderline high LD L level
159
160 to 4 .110 4.9 High LOL level
189
>190 >4.9 Very high l Dl level, corresponding to highest increased risk of
heart dis.ease
These guidelines were based on a goal of presumably deneas.ng death rates from
cardiovascular disease to less th an 2% to 3% per year or less than 20% to 30% every
10 years. Note that 100 is not considered optimal; less than 100 is optim al, though 1 is
unspecified how much less
Function
VLDL transports endogenous triglycerides , phospholipids, cholesterol, and choIesteryl
esters. It functions as the body's internal transport mechanism for lipids.
In general, IOL, somewhat similar to low-density lipoprotein (LOL ), transports a variety of
triglyceride fats and cholesterol and, like LD L, can also promote the growth of atheroma.
High -density lipoprotein (HOL) is one of the five major groups of lipoproteins
(chylomicrons , VLDL, IDL, LDL, HDL) lt1at en able lipids like cholesterol and triglycerides
to be transported within the water-based bloodstre<lffi. In heallt1y individuals, about thirty
percent of blood cholesterol is carried by HDLl l)
It is hypothesized that HOL can remove cholesterol from atheroma within arteries and
transport it back to the liver for excretion or re -utilization, which is the main reason why
HDL -bound cholesterol is sometimes called " good cholesterol" , or HDL-C. A high level
of HOL -C seems to protect against cardiovascula r diseases, and low HDL cholesterol
levels (less than 40 mgldL or about lmmolll) increase the risk for heart disease P1
Cholesterol contained in HOL particles is considered beneficial for the cardiovascular
health , in contrast to "bad" LDL cholesterol.

8. Recommended range
The American Heart Association , NIH and NCEP provides a set of guidelines for fasting
HDL levels and risk for heart disease [5116][7]
Level mgfdl level Interpremion
mmoliL
<40 for men, <50 < 1.03 low HDl cholesterol , heightened risk for heart disease
for women
40-09 1.03- Medium HDllevel
1.55
>60 >1 .55 High HDL level, optimal condition cOflsidered
protective against heart disease