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8/7/2019 LIPOPROTEIN IN HEALTH AND DISEASE
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LIPOPROTEIN IN HEALTH AND
DISEASE
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A LIPOPROTEIN is a biochemical assembly that
contains both PROTEINS and LIPIDS water-boundto the proteins.
Many enzymes, transporters, structural proteins,antigens, adhesins and toxins are lipoproteins.
Examples include the high density (HDL) and lowdensity (LDL) lipoproteins
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ELECTRON MICROSCOPIC IMAGES OF NEGATIVE
STAINED LIPOPROTEINS
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ANATOMY OF A LIPOPROTEIN
Fig. 25-1
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LIPOPROTEIN STRUCTURE(chylomicron)
ApoA, ApoB, ApoC, ApoE (apolipoproteins); T
(triacylglycerol); C (cholesterol); green (phospholipids)
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COMPOSITION AND RELATIVE SIZE OF
LIPOPROTEINS
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Table 251. Composition of the Lipoproteins in Plasma of Humans.
Lipoprotein Source Diameter
(nm)
Density
(g/mL)
Protein
(%)
Lipid (%) Main Lipid
Components
Apolipoproteins
Chylomicrons Intestine 901000 < 0.95 12 9899 Triacylglycerol A-I, A-II, A-IV,1
B-
48, C-I, C-II, C-III,E
Chylomicron
remnants
Chylomicrons 45150 < 1.006 68 9294 Triacylglycerol,
phospholipids,cholesterol
B-48, E
VLDL Liver (intestine) 3090 0.951.006 710 9093 Triacylglycerol B-100, C-I, C-II, C-
III
IDL VLDL 2535 1.0061.019 11 89 Triacylglycerol,
cholesterol
B-100, E
LDL VLDL 2025 1.0191.063 21 79 Cholesterol B-100
HDL Liver, intestine, VLDL,
chylomicrons
Phospholipids,
cholesterol
A-I, A-II, A-IV, C-
I, C-II, C-III, D,2
E
HDL1 2025 1.0191.063 32 68
HDL2 1020 1.0631.125 33 67
HDL3 510 1.1251.210 57 43
Pre-HDL3
< 5 > 1.210 A-I
Albumin / free fatty
acids
Adipose tissue > 1.281 99 1 Free fatty acids
Abbreviations: HDL, high-density lipoproteins; IDL, intermediate-density lipoproteins; LDL, low-density lipoproteins; VLDL, very low density lipoproteins.
1Secreted with chylomicrons but transfers to HDL.
2Associated with HDL2 and HDL3 subfractions.
3Part of a minor fraction known as very high density lipoproteins (VHDL).
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CLASSIFICATION
BY DENSITY
Lipoproteins may be classified as follows,listed from larger and less dense to smaller
and denser. Lipoproteins are larger and less
dense, if they consist of more fat than ofprotein. They are classified on the basis of
electrophoresis and ultracentrifugation.
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CHYLOMICRONS CARRY TRIGLYCERIDES (fat) from theintestines to the liver, skeletal muscle, and to adipose tissue
VERY LOW DENSITY LIPOPROTEINS (VLDL) carrytriacylglycerol from the liver to adipose tissue.
INTERMEDIATE DENSITY LIPOPROTEINS (IDL) areintermediate between VLDL and LDL. They are not usually
detectable in the blood.
LOW DENSITY LIPOPROTEINS (LDL) carry cholesterol fromthe liver to cells of the body. LDLs are sometimes referred to
as the "bad cholesterol" lipoprotein.
HIGH DENSITY LIPOPROTEINS (HDL) collect cholesterolfrom the body's tissues, and bring it back to the liver. HDLsare sometimes referred to as the "good cholesterol"
lipoprotein
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ALPHA AND BETA :
It is also possible to classify lipoproteins as "alpha"
and "beta", according to the classification of
proteins in serum protein electrophoresis.
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LIPOPROTEIN(a)
Lipoprotein(a) L p(a), Cardiology diagnostic
tests
< 14 mg/d L : Normal 14-19 mg/d L : ? > 19
mg/d L : High risk
How to lower: aerobic exercise, niacin, aspirin
etc.
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PATHOLOGY
Lipoprotein's structure is similar to plasminogenand tPA (tissue plasminogen activator) and it
competes with plasminogen for its binding site,
leading to reduced fibrinolysis
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ISOLATION OF LIPOPROTEINS BY ULTRA-
CENTRIFUGATION
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METABOLISM
The handling of lipoproteins in the body is
referred to as "lipoprotein metabolism'.
It is divided into two pathways, EXOGENOUS
and ENDOGENOUS
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FUNCTION
The basic function of lipoprotein particles is toTRANSPORT LIPIDS (fats) around the body in theblood.
All cells use and rely on fats and cholesterol asbuilding blocks to create the multiple membranes
which cells use to both control internal watercontent, internal water soluble elements and toorganize their internal structure and proteinenzymatic systems.
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The lipoprotein particles have hydrophilic groups of
phospholipids, cholesterol and apoproteins directedoutward. Such characteristics makes them soluble
in the salt water-based blood pool.
Triglyceride-fats and cholesterol esters are carried
internally, shielded from the water by the
phospholipid monolayer and the apoproteins.
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The interaction of the proteins forming the surface
of the particles with :
(a) enzymes in the blood,(b) with each other, and
(c) with specific proteins on the surfaces of cells
determine whether triglycerides and cholesterolwill be added to or removed from the lipoprotein
transport particles.
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CLINICAL IMPLICATIONS OF
LIPOPROTEINS
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BLOOD LIPID LEVELS
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BLOOD LIPID LEVELS
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Initial detailed analysis of plasma LDL in control subjects and CHD patients with hypertriglyceridemia and
low HDL have revealed the presence of two distinct major lipoprotein phenotypes based on LDL
subclasses. One subclass is characterized by a predominance of large buoyant LDL particles (pattern A),
and the second subclass is characterized by small, dense LDL particles (pattern B). Pattern B is often
associated with hypertriglyceridemia and low HDL, and is frequently referred to as the atherogenic
lipoprotein profile.
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GENETIC DISORDERS
Familial Hypercholesterolemia
Types
* Heterozygous FH (incidence 1:500-1,000)
* Homozygous FH (incidence 1:1,000,000)
CausesBoth forms are caused by the same problem: a mutation in
either the LDL receptor or the ApoB protein. There is one
known ApoB defect (R3500Q) and a multitude of LDL receptor
defects, the frequency of which is different for each population.
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Lipoprotein (a) and Heart Disease
Lipoprotein (a) (L p (a)) issimilar in structure to lowdensity lipoprotein (LDL), but
is attached to a glycoproteinknown as apolipoprotein (a).
The apolipoprotein portion is
similar in structure toplasminogen. Similar to otherlow density lipoproteins,Lp(a) contains cholesterol
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How does Lp(a) Increase the Risk of
Heart Disease
Several mechanisms have been proposed to explain the relationship
between Lp (a) and heart disease. Apo(a) has a sticky adhesive nature,
making it easy to attach LDL, calcium and other components into an a
atherosclerotic plaque on the blood vessel wall (endothelium). Lp (a)
has been associated with endothelial dysfunction as well. Due to its
structural similarity with plasminogen, Lp (a) competes for binding with
fibrin, thereby inhibiting the breakdown of fibrin. This action could
promote blood clot formation. Finally, Lp (a) activates immune cells
including monocytes and macrophages, and could induce inflammation.All of these effects help to induce plaque formation, and to promote clot
formation after the plaque is ruptured. Apparently, Lp(a) is attracted to
the artery wall by means of Lysine Binding Sites that become exposed
when the endothelial wall is damaged.