LIPOPROTEINS

PESENTED BY :MANJUNATH D

Lipoproteins are biochemical assembly that contains both proteins and lipids. Lipoproteins are made up of different molecules that interact with water insoluble fats molecules and transports those fats in the plasma. Lipids are insoluble in water, the problem of transportation in the aqueous plasma is solved by associating nonpolar lipids with amphipathic lipids and proteins to make water miscible lipoproteins.

INTRODUCTION

consist of a nonpolar core and a single surface layer of amphipathic lipids.

The nonpolar lipid core (triacylglycerol and cholesteryl ester) and amphipathic (phospholipids and cholesterol )molecules.

The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein.

General Structure of Lipo proteins

Lipoproteins can be classified in three ways-1. Based on density- They are separated by

Ultracentrifugation. Depending upon the floatation constant, 5 major groups are identified.

(i) Chylomicons, Derived from intestinal absorption of triacylglycerol and other lipids. Transports exogeneous triglycestrides ,from intestine to the liver.

(ii) Very low density lipoproteins (VLDL), Derived from the liver for the export of triacylglycerol. Transport of triglycerides from the liver to tissues for storage and energy.

Classification of Lipoproteins

1) Based on density (contd.)(iii) Intermediate density lipoproteins (IDL) are

derived from the catabolism of VLDL.(iv) Low-density lipoproteins (LDL),

representing a final stage in the catabolism of VLDL. Transports cholesterol to peripheral tissues.

(v) High-density lipoproteins (HDL), involved in cholesterol transport and also in VLDL and chylomicron metabolism. Transports cholestrol away from the peripheral tissues to the liver.

Classification of Lipoproteins

Classification of Lipoproteins

As the lipid content increases ,density decreases and size increases, that is why chylomicrons are least dense but biggest in size, while HDL are rich in proteins, hence most dense but smallest in size.

2) Based on electrophoretic mobilities

Lipoproteins may be separated according to their electrophoretic properties into - α, pre β, β, and broad beta lipoproteins. The mobility of a lipoprotein is mainly dependent upon protein content. Those with higher protein content will move faster towards the anode and those with minimum protein content will have minimum mobility.

Classification of Lipoproteins

3) Based on nature of Apo- protein content One or more apolipoproteins (proteins or

polypeptides) are present in each lipoprotein. The major apolipoproteins of HDL (α-lipoprotein) are

designated A. The main apolipoprotein of LDL (β -lipoprotein) is

apolipoprotein B (B-100), which is found also in VLDL.

Chylomicons contain a truncated form of apo B (B-48) that is synthesized in the intestine, while B-100 is synthesized in the liver.

Apo E is found in VLDL, HDL, Chylomicons, and chylomicron remnants.

Classification of Lipoproteins

• Locate in extracellular on the walls of blood capillaries, anchored to the endothelium.

• Hydrolyze triglyceride (TG) in the core of CM and VLDL to free fatty acids and glycerol.

• The free fatty acids are transported into the tissue, mainly adipose, heart, and muscle (80%), while about 20% goes indirectly to the liver.

Important enzymes and proteins involved in lipoprotein metabolism

LPL (Lipoprotein Lipase)

• Bound to the surface of liver cells, Hydrolyzes TG to free fatty acids and glycerol

• Unlike LPL, HL does not react readily with CM or VLDL but is concerned with TG hydrolysis in VLDL remnants and HDL metabolism.

HL (Hepatic Lipase)

LCAT (Lecithin:Cholesterol Acyltransferase)

Formation of cholesterol esters in lipoproteins

CETP (Cholesterol Ester Transfer Protein)

Apolipoproteins

LpL inhibitor;inflammatory signaling pathways.

apoC-III

LpL activator.apoC-II

Inhibit Lp binding to LDL R; LCAT activatorapoC-I

apoB-48

Structural protein of all LP except HDL.Lacks receptor-binding domain of B 100.

apoB100

Tg metabolism;LCAT activator.apoA-IV

HL activationapoA-II

HDL structural protein; activates LCAT.apoA-I

(1) They can form part of the structure of the lipoprotein, e.g. apo B, structural component of VLDL and Chylomicons

(2) They are enzyme cofactors, e.g. C-II for lipoprotein lipase, A-I for lecithin: cholesterol acyl transferase (LCAT), or enzyme inhibitors, eg, apo A-II and apo C-III for lipoprotein lipase, apo C-I for cholesteryl ester transfer protein

(3) They act as ligands for interaction with lipoprotein receptors in tissues, e.g. apo B-100 and apo E for the LDL receptor, apo A-I for the HDL receptor.

Functions of Apo proteins

Metabolism of chylomicrons

Metabolism of VLDL and LDL

HDL and Reverse Cholesterol Transport

HDL and Reverse Cholesterol Transport

HDL and Reverse Cholesterol Transport

LDL-RApo b

Lipoprotein –related diseasesDisorder Defect Comments

Wolman diseases(cholesteryl ester storage disease)

Defect in lysosomal cholesteryl ester hydrolase;affects metabolism of LDLs.

Reduced LDL clearance leads to hypercholesterolemia, resulting in atherosclerosis and coronary artery disease.

Tangier disease Reduced HDL concentrations,noeffect on chylomicron or VLDL production.

Tendency to hypertriglycerideemia;some elevation in VLDLs;hypertrophic tonsils with orange appearance.

Lipoprotein –related diseasesDisorder Defect Comments

Heparin-releasable hepatic triglyceride lipase deficiency

Deficiency of the lipase leads to accumulation of TG-rich HDLs and VLDL remnants (IDLs)

Causes xanthomas and coronary artery disease.

LCAT deficiency Norum disease

Absence of LCAT leads to inability of HDLs to take up cholesterol .

Decrease levels of plasma cholesteryl esters and lysolecithin.

Lipoproteins are an important class of biomolecules that have diverse functions.

Their association with lipids for the purpose of transport and storage make them a vitial part of lipid function.

Lipoproteins serve as excellent markers for cardivascular diseases and other lipid related disorders.

Conclusion