lipoprotein in health and disease

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.

lipoprotein in health and disease

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