2. Apo lipoproteins structure and
function
Name :Eman abd el raouf ahmed
Under supervision :Prof. Dr.Magda Megahed
3. Definition
Apo lipoproteins are the protein
components of lipoproteins, the lipid–
protein complexes responsible for
transporting lipids in the blood. They may
have additional specialized functions that
are encoded by their genes..
http://www.els.net/WileyCDA/ElsArticle/ref
Id-a0005909.html
4. structure
Lipoproteins are spherical (VLDL, LDL, HDL) in shape with a core of
non-polar lipids, triacylglycerols and cholesterol esters, and a
surface monolayer, consisting of apoproteins, phospholipids and
non-esterified cholesterol, which serves to present a hydrophobic
face to the aqueous phase
5. Classification
the main groups are classified as chylomicrons (CM),
very-low-density lipoproteins (VLDL), low-density
lipoproteins (LDL) and high-density lipoproteins (HDL),
based on the relative densities of the aggregates on
ultracentrifugation.
these classes can be further refined by improved
separation procedures, and intermediate-density
lipoproteins (IDL) and subdivisions of the HDL (e.g. HDL1,
HDL2, HDL3 and so forth) are often defined, and each of
these may have distinctive apoprotein compositions and
biological properties that are relevant to cardiovascular
disease.
6. Composition and structure
Lipoproteins are complex aggregates of lipids and proteins that
render the lipids compatible with the aqueous environment of body
fluids and enable their transport throughout the body of all
vertebrates and insects to tissues where they are required.
Lipoproteins are synthesized mainly in the liver and intestines. Within
the circulation, these aggregates are in a state of constant flux,
changing in composition and physical structure as the peripheral
tissues take up the various components before the remnants return to
the liver.
7. structure
Apo B100 and apo B48 large and water-insoluble
they are the only non-exchangeable apoproteins,
which are assembled into triacylglycerol-rich
lipoproteins with their lipid components in the
intestines or liver.
Cholesterol esters are required for proper folding
of apo B. With 4536 amino acid residues, apo
B100 is one of the largest monomeric proteins
known; apo B48 represents the N-terminal 48%
of apo B100.
8. From genes to proteins
Structural organization of the human Apo lipoprotein (Apo) A‐I, A‐II, A‐IV,
C‐I, C‐II, C‐III and E genes. The wide bars represent the exons and are
divided into several regions: the open bars at the two ends represent the 5′
and 3′ un translated regions; the hatched bars, the signal peptide regions;
and the solid bars, the mature peptide regions of the respective genes.
9. THE DISTRIBUTION OF
APOLIPOPROTEIN E GENOTYPE
• Apolipoprotein E (ApoE) is encoded by the codominant alleles ε2, ε3, and ε4,
resulting in 6 bi-allelic genotypes
• The corresponding protein isoforms differ in their lipoprotein receptor
affinity, antioxidant activity, and inflammation modulatory properties
• APOE ε4 carriership is associated with an increased risk of atherosclerosis
and dementia
• Approximately 65%–75% of patients with Alzheimer's disease carry the ε4
allele
• http://aje.oxfordjournals.org/content/early/2015/01/21/aje.kwu442
10. physical properties
The physical properties of Apo proteins enable them to
bind readily at the interface between water and
phospholipids, and specifically they bind to the
phospholipids on the surface of the lipoproteins. In
effect, this outer shell of amphipathic lipids and proteins
solubilizes the hydrophobic lipid core in the aqueous
environment.
http://lipidlibrary.aocs.org/Lipids/lipoprot/index.htm
13. Apo A1
is the main protein component of HDL, and is synthesised within the liver
(70%) and intestine (30%). It is a 28-kDa single polypeptide consisting of 243-
amino acids, which has no disulfide linkages or glycosylation. Apart from the
44 amino acid N-terminal region, the protein is arranged as eight α-helical
segments of 22 amino acids with two 11-mer repeats.
Apo A2 is the second most important HDL apolipoprotein, and it exists as a
homodimer with two polypeptide chains, each 77 amino acids in length and
linked by a disulfide bond.
Human apo A4 is the largest member of the exchangeable apolipoprotein
family and is a 376-amino acid glycoprotein, which is synthesised in intestinal
enterocytes and secreted as a constituent of chylomicrons
14. Apo protein(a) is an Adhesive Protein
The apo(a) molecule contains the arginine-glycine-aspartate sequence
characteristic of adhesive proteins
Properties such as organ morphogenesis, differentiation, and
growth have recently been discovered to be associated with a
number of proteins present in the extracellular matrix and the
blood, such as fibronectin, collagen, laminin, vitronectin,
osteopontin including also coagulation factors such as fibrinogen
.These ‘adhesive proteins’ contain a characteristic amino-acid
sequence: arginine-glycine-aspartate (RGD), by means of which
they interact with integrins, a family of cell surface receptors for
adhesive proteins.
15. Detection of apo(a) in human
sperm
o When human sperm was analysed in our
laboratory, both the seminal plasma and the
cellular fraction were found to contain apo(a).
o We could not detect any apo B associated with
this apo(a).
16. The role of the adhesive protein apo(a) under pathological
conditions
Apo(a) co-ordinates the interaction between cellular systems and the
extracellular matrix during repair processes. Apo(a) is involved in tissue
reformation during acute repair processes such as wound-healing .
They interact specifically with cellular systems such as monocytes, T cells as well
as thrombocytes and thereby play a critical role in inflammatory, infectious,
hemostatic and many other processes
The elevation of ap(a) plasma levels as established for cancer, cardiovascular,
inflammatory and many other diseases is additional confirmation for this concept.
17. Apo B
is a protein that is involved in the metabolism of lipids and is the main protein
constituent of lipoproteins such as very low-density lipoprotein (VLDL) and
low-density lipoprotein (LDL, the "bad cholesterol"). Concentrations of apo B
tend to mirror those of LDL-C.
Apo B levels may be ordered to monitor the effectiveness of lipid treatment as
an alternative to non-HDL-C (non-HDL-C is the total cholesterol concentration
minus the amount of HDL).
18. Where is the APOB gene
located?
Cytogenetic Location: 2p24-
p23
Molecular Location on
chromosome 2
19. the normal function of the APOB
gene
The APOB gene provides instructions for making two versions of
the apolipoprotein B protein, a short version called
apolipoprotein B-48 and a longer version known as
apolipoprotein B-100. Both of these proteins are components of
lipoproteins, which are particles that carry fats and fat-like
substances (such as cholesterol) in the blood.
Apolipoprotein B-48 is produced in the intestine, where it is a
building block of a type of lipoprotein called a chylomicron. As
food is digested after a meal, chylomicrons are formed to carry
fat and cholesterol from the intestine into the bloodstream.
Chylomicrons are also necessary for the absorption of certain
fat-soluble vitamins such as vitamin E and vitamin A.
20. How are changes in the APOB gene related to
health conditions?
More than 90 mutations in the APOB gene
have been found to cause familial
hypobetalipoproteinemia (FHBL), a disorder
that impairs the body's ability to absorb and
transport fat. Most APOB gene mutations that
cause FHBL lead to the production of
apolipoprotein B that is abnormally short.
21. hypercholesterolemia - caused
by mutations in the APOB gene
At least five mutations in the APOB gene are known to cause a form of inherited
hypercholesterolemia called familial defective apolipoprotein B-100 (FDB).
This condition is characterized by very high levels of cholesterol in the blood
and an increased risk of developing heart disease. Each mutation that causes
this condition changes a single protein building block (amino acid) in a critical
region of apolipoprotein B-100.
22. What does the test result mean?
Abnormal levels of apo B can also be caused by underlying
conditions or other factors (secondary causes). Increased levels of
apo B are seen, for example, in:
Diabetes
Use of drugs such as: androgens, beta blockers, diuretics,
progestins (synthetic progesterones)
Hypothyroidism
Nephrotic syndrome (a kidney disease)
Pregnancy (levels increase temporarily and decrease again after
delivery)
23. Apo B levels
may be decreased with any condition that affects lipoprotein
production or affects its synthesis and packaging in the liver. Lower
levels are seen with secondary causes such as:
Use of drugs such as: estrogen (in post-menopausal women), lovastatin,
simvastatin, niacin, and thyroxine
Hyperthyroidism
Malnutrition
Reye syndrome
Weight reduction
Severe illness
Surgery
Cirrohsis
An increased ratio of apo B to apo A-I may indicate a higher risk of
developing CVD.
http://labtestsonline.org/understanding/analytes/apob/tab/test/
24. APO E
is an O-linked glycoprotein in three isoforms
and is synthesised by many tissues, including
liver, brain, adipose tissue, and artery wall, but
most is present in plasma lipoproteins derived
primarily from the liver.
25. The function of APO E
Apolipoprotein E has many functions in the body. When it is synthesized by the liver
as part of VLDL it functions in the transport of triglycerides to the liver tissue. It is also
incorporated into HDL (as HDL-E) and functions in cholesterol distribution among cells.
It is also incorporated into intestinally synthesized cholymicrons and transports
dietary triglycerides and cholesterol.
Apolipoprotein E is synthesized in several areas of the body. Approximately three-
fourths of the plasma apo-E is synthesized in the liver. Liver apo-E is produced
primarily by hepatic parenchymal cells, and it becomes a component of VLDL. The
brain also produces a large amount of apo-E.
http://wwwchem.csustan.edu/chem4400/SJBR/Dawn971.htm
26. Isoforms of APO E
There are three different isoforms of apolipoprotein E: apo-E 2, apo-E 3, And apo-E 4.
Apo-E 3 is the parent form and all others are compared to it. Apo-E 2 is different from
apo-E 3 because a cysteine is substituted for arginine at residue 158. Apo-E 2 is
associated with Type III Hyperproteinemia (where there is an excess of protein in the
blood plasma) and it does not bind to the lipid receptor.
http://wwwchem.csustan.edu/chem4400/SJBR/Dawn971.htm
27. Apo D
is atypical in that it is very different in structure from
other apolipoproteins, and it is expressed widely in
mammalian tissues (most others are produced
mainly in liver and intestine). In plasma, it is present
mainly in HDL and to a lesser extent in LDL, where it
may function as a multi-ligand binding protein
capable of transporting small hydrophobic molecules
such as arachidonic acid, steroid hormones, and
cholesterol for metabolism or signalling.
http://www.uniprot.org/uniprot/P05090
