2. Apolipoproteins structure and
function
Name:eman abdelraouf ahmed

3. The content
Definition
Structure
Function
references

4. introduction
Plasma lipoprotein metabolism is
regulated and controlled by the specific
apolipoprotein (apo-) constituents of the
various lipoprotein classes. The major
apolipoproteins include apoE, apoB,
apoA-I, apoA-II, apoA-IV, apoC-I, apoC-II,
and apoC-III.

7. Apolipoprotein B (ApoB)
is a protein that in humans is encoded by
the APOBgene.

8. Function
Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, IDL,
andLDL particles (LDL - known commonly by the misnomer "bad cholesterol"
when in reference to both heart disease and vascular disease in general),
which is responsible for carrying fat molecules (lipids), including cholesterol,
around the body (within the water outside cells) to all cells within all tissues.
it is the primary organizing protein (of the entire complex shell
enclosing/carrying fat molecules within) component of the particles and is
absolutely required for the formation of these particles. What is also clear is
that the ApoB on the LDL particle acts as a ligand for LDL receptors in various
cells throughout the body (i.e., less formally, ApoB indicates fat carrying
particles are ready to enter any cells with ApoB receptors and
deliver fats carried within into the cells).

9. Genetic disorders
High levels of ApoB are related to heart
disease. Hypobetalipoproteinemia is a genetic disorder that
can be caused by a mutation in the ApoB
gene, APOB. Abetalipoproteinaemia is usually caused by a
mutation in the MTP gene, MTP.
Mutations in gene APOB100 can also cause familial
hypercholesterolemia, a hereditary (autosomal dominant)
form of metabolic disorderHypercholesterolemia.

10. Specific apolipoproteins function in the regulation of
lipoprotein metabolism through their involvement in
the transport and redistribution of lipids among various
cells and tissues, through their role as cofactors for
enzymes of lipid metabolism, or through their
maintenance of the structure of the lipoprotein
particles. The primary structures of most of the
apolipoproteins are now known, and various functional
domains of these proteins are being mapped using
selective chemical modification, synthetic peptides, and
monoclonal antibodies.

11. apoE
Apolipoprotein E (ApoE) is a class
of apolipoprotein found in
the chylomicronand Intermediate-density
lipoprotein (IDLs) that is essential for the normal
catabolism of triglyceride-rich lipoprotein
constituents.
ApoE is mainly produced by astrocytes, and
transports cholesterol toneurons via ApoE
receptors, which are members of the low density
lipoprotein receptor gene family.

12. Function
APOE is 299 amino acids long and
transports lipoproteins, fat-soluble vitamins,
and cholesterol into the lymph system and then
into the blood.
.

13. It is synthesized principally in the liver, but has also been found in other
tissues such as the brain,kidneys, and spleen. In the nervous system, non-
neuronal cell types, most notablyastroglia and microglia, are the primary
producers of APOE, while neurons preferentially express the receptors for
APOE. There are seven currently identified mammalian receptors for APOE
which belong to the evolutionarily conserved low density lipoprotein receptor
gene family

14. APOE was initially recognized for its
importance in lipoprotein metabolism
andcardiovascular disease. Defects in APOE
result in familial
dysbetalipoproteinemiaaka type
III hyperlipoproteinemia (HLP III), in which
increased plasma cholesteroland
triglycerides are the consequence of
impaired clearance
of chylomicron, VLDLand LDL remnants

15. More recently, it has been studied for its role in several biological processes
not directly related to lipoprotein transport, includingAlzheimer's
disease (AD), immunoregulation, and cognition.

16. In the field of immune regulation, a growing number of
studies point to APOE's interaction with many
immunological processes, including suppressing T
cellproliferation, macrophage functioning regulation,
lipid antigen presentation facilitation
(by CD1) to natural killer T cell as well as modulation
of inflammationand oxidation. ApoE is produced by
macrophages and apoE secretion has been shown to be
restricted to classical monocytes in PBMC, and the
secretion of apoE by monocytes is down regulated by
inflammatory cytokines and upregulated by TGF-beta.

17. apoA-I
Apolipoprotein A1 is a protein that in humans is encoded by the APOA1gene.
It has a specific role in lipid metabolism. Recent report suggest thatAPOA1 mRNA
is regulated by endogenously expressed antisense RNA.
Apolipoprotein A1 is the major protein component of high density
lipoprotein (HDL) in plasma. Chylomicrons secreted from the intestinal
enterocyte also contain apo A1, but it is quickly transferred to HDL in the
bloodstream.
The protein promotes fat efflux, including cholesterol, from tissues to the liver
for excretion. It is a cofactor for lecithin cholesterolacyltransferase (LCAT) which
is responsible for the formation of most plasma cholesteryl esters. Apo A1 was
also isolated as aprostacyclin (PGI2) stabilizing factor, and thus may have an
anticlotting effect.

18. ApoA1 is often used as a biomarker for
prediction of cardiovascular diseases
and the ratio apoB- 100/apoA1 has
been reported as a stronger predictor
for the risk of myocardial infarction
than any other lipid
measurement. ApoA1 is routinely
measured using immunoassays such
as ELISA or nephelometry.

19. Clinical significance
As a major component of the high-density
lipoprotein complex (protective "fat removal" particles),
apo A1 helps to clear fats, including cholesterol, from white
blood cells within artery walls, making the WBCs less likely
to become fat overloaded, transform into foam cells, die
and contribute to progressive atheroma. Five of nine men
found to carry a mutation (E164X) who were at least 35
years of age had developed premature coronary artery
disease.One of four mutants of apo A1 is present in roughly
0.3% of the Japanese population, but is found in 6% of
those with low HDL cholesterol levels.

20. Apolipoprotein A-II
is a protein that in humans is encoded by
the APOA2 gene.
This gene encodes apolipoprotein (apo-) A-II,
which is the second most abundant protein of the
high density lipoprotein particles. The protein is
found in plasma as a monomer, homodimer, or
heterodimer with apolipoprotein D. Defects in this
gene may result in apolipoprotein A-II deficiency or
hypercholesterolemia.

21. apoA-IV
The primary translation product of the APOA4
gene is a 396-residue preprotein, which
undergoes proteolytic processing to yield apo
A-IV, a 376-residue mature O-linked
glycoprotein. In most mammals, including
humans, apo A-IV synthesis is confined to
the intestine; however in mice and rats
hepatic synthesis also occurs.

22. Apo A-IV is secreted into circulation on the surface of newly
synthesizedchylomicron particles. Intestinal fat absorption
dramatically increases the synthesis and secretion of apo A-IV.
Although its primary function in human lipid metabolism has
not been established, apo A-IV has been found to:
activate lecithin-cholesterol
acyltransferase and cholesterylester transfer protein in vitro;
play a role in the regulation of appetite and satiety in rodent
models;
display anti-oxidant and anti-atherogenic properties in vitro
and in rodent models;
modulate the efficiency of enterocyte and hepatic
transcellular lipid transport in vitro.

23. apoC-I
is a protein component
of lipoproteins that in humans is
encoded by the APOC1 gene.

24. apoC-I-structure
The protein encoded by this gene is a member of
the apolipoprotein C family. This gene is expressed
primarily in the liver, and it is activated
when monocytesdifferentiate into macrophages.
A pseudogene of this gene is located 4 kb downstream in
the same orientation, on the same chromosome. This
gene is mapped to chromosome 19, where it resides
within an apolipoprotein gene cluster. Alternatively
spliced transcript variants have been found for this gene,
but the biological validity of some variants has not been
determined.

25. Apolipoprotein C1 has a length of 57 amino
acids normally found in plasma and responsible for
the activation of esterified lecithin cholesterol with an
important role in the exchange of esterified
cholesterol between lipoproteins and in removal of
cholesterol from tissues. Its main function is inhibition
of CETP, probably by altering the electric
charge of HDL molecules.

26. During fasting (like other apolipoprotein C), it is found
primarily within HDL, while after a meal it is found on
the surface of other lipoproteins. When proteins rich in
triglycerides like chylomicrons and VLDL are broken
down, this apoprotein is transferred again to HDL. It is
one of the most positively charged proteins in the
human body.

27. Apolipoprotein C2
The protein encoded by this gene is secreted in plasma
where it is a component ofvery low density
lipoproteins and chylomicrons. This protein activates the
enzymelipoprotein lipase in capillaries,[1] which hydrolyzes
triglycerides and thus provides free fatty acids for cells.
Mutations in this gene cause hyperlipoproteinemia type IB,
characterized by xanthomas, pancreatitis, and
hepatosplenomegaly, but no increased risk
for atherosclerosis. Lab tests will show elevated blood
levels of triglycerides, cholesterol, and chylomicrons.

28. apo-CIII
also known as apo-CIII is
a protein that in humans is encoded
by the APOC3 gene. Apo-CIII is a
component of very low density
lipoprotein (VLDL).

29. Structure
ApoCIII is a relatively small protein containing 79
amino acids that can be glycosylated at threonine-
74.The most abundant glycoforms are
characterized by an O-linked disaccharide
galactose linked to N-acetylgalactosamine (Gal-
GalNAc), further modified with up to 2 sialic
acid residues. Less abundant glycoforms are
characterized by more complex
and fucosylated glycan moieties.

30. Function
APOC3 inhibits lipoprotein lipase and hepatic lipase; it is
thought to inhibit hepatic uptake[.of triglyceride-rich
particles. The APOA1, APOC3 and APOA4 genes are closely
linked in both rat and human genomes. The A-I and A-IV
genes are transcribed from the same strand, while the A-1
and C-III genes are convergently transcribed. An increase in
apoC-III levels induces the development
ofhypertriglyceridemia. Recent evidences suggest an
intracellular role for Apo-CIII in promoting the assembly and
secretion of triglyceride-rich VLDL particles from hepatic
cells under lipid-rich conditions. However, two naturally
occurring point mutations in human apoC3 coding sequence,
namely Ala23Thr and Lys58Glu have been shown to abolish
the intracellular assembly and secretion of triglyceride-rich
VLDL particles from hepatic cells.

31. Clinical significance
Two novel susceptibility haplotypes (specifically,
P2-S2-X1 and P1-S2-X1) have been discovered in
ApoAI-CIII-AIV gene
cluster onchromosome 11q23; these confer
approximately threefold higher risk of coronary
heart disease in normal as well as non-
insulindiabetes mellitusApo-CIII delays the
catabolism of triglyceride rich particles.
Elevations of Apo-CIII found in genetic variation
studies may predispose patients to non-alcoholic
fatty liver disease.

32. references
http://www.scientificpsychic.com/health/lipoprot
eins-LDL-HDL.html