CHEMISTRY OF LIPOPROTEINS

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Lipoproteins Gandham.Rajeev Email:[email protected]

Transcript of CHEMISTRY OF LIPOPROTEINS

Lipoproteins

Gandham.RajeevEmail:[email protected]

Introduction

• Lipoproteins are molecular complexes that

consist of lipids & proteins (conjugated

proteins).

• Protein part is called apolipoprotein.

• Usually abbreviated as Lp.

• They function as transport vehicles for lipids in

blood plasma.

• Lipoproteins deliver the lipid components

(cholesterol, TAG etc.) to tissues for utilization.

Classification of lipoproteins

• Depending on the density by

ultracentrifugation or electophoretic mobility,

the lipoproteins are classified as 5 major types.

1. Chylomicrons-contains apoprotein B48.

2. Very low density lipoproteins (VLDL) or

prebeta lipoproteins.

• Main apoprotein is B-100.

3. Intermediate density lipoproteins (IDL) or

broad-beta lipoproteins.

4. Low density lipoproteins (LDL) or

betalipoproteins.

• Major apoprotein in LDL is B-100.

5. High density lipoproteins (HDL) or

alphalipoproteins.

• Major apoprotein in HDL is apo-A.

• Free fatty acids (FFA) or nonesterified fatty

acids (NEFA) are complexed with albumin.

Chylomicrons

• Synthesized in the intestine & transport

exogenous (dietary) TAGs to various tissues.

• Contains apoprotein B-48.

• They consist of highest (99%) quantity of lipid &

lowest (1%) concentration of protein.

• The chylomicrons are the least in density &

largest in size.

Very low density lipoproteins (VLDL)

• Pre β-lipoproteins.

• Main apoprotein is B-100.

• They are produced in liver & intestine.

• Responsible for the transport of

endogenously synthesized triacylglycerols.

Low density lipoproteins (LDL)

• β-lipoprotein.

• They are formed from VLDL in the blood

circulation.

• They transport cholesterol from liver to other

tissues.

High density lipoproteins (HDL)

• α-lipoproteins.

• Major apoprotein in HDL is apo-A.

• They are mostly synthesized in liver.

• Three different fractions of HDL (1, 2 & 3)

identified by ultracentrifugation.

• HDL particles transport cholesterol from

peripheral tissues to liver (reverse cholesterol

transport).

Free fatty acids or non-esterified fatty acids

• Free fatty acids or non-esterified fatty acids

(NEFA) are complexed with albumin.

• Loosely bound to the protein-albumin.

• Each molecule of albumin can hold about 20-30

molecules of free fatty acids.

Structure of lipoproteins

• Lipoprotein consists of inner core (hydrophobic

triacylglycerol, cholesterylester & tails of

phospholipids) surrounded by a coat shell of

phospholipids, apoproteins & cholesterol.

• The polar head portions (hydrophilic) of

phospholipids & cholesterol are exposed on

the surface of lipoproteins.

• So that lipoprotein is soluble in aqueous

solution.

• The apoproteins also increase the solubility of

lipids.

Apo-lipoproteins

• Protein part of lipoprotein is called as

apolipoprotein (apo-Lp) or apoprotein.

• Synthesis:

• All apoproteins are synthesized in liver.

• Small quantities are produced from almost all

organs.

• Intestinal cells produce small quantities of

apo-A.

• They will solubilize the lipid part.

Functions of apolipoproteins

• Apo A-1:

• It activates LCAT.

• It is the ligand for HDL receptor.

• It is anti-atherogenic.

• It is specific for HDL.

• Apo B-100:

• Only apoprotein component of LDL.

• It binds to LDL receptors on tissues.

• It is one of the biggest proteins, having 4536

amino acids, & molecular weight is 550 kDa.

• Synthesized in liver.

• Apo B-48:

• Major apoprotein of chylomicrons.

• Synthesized only in intestinal cells.

• Apo-B-100 & apo-B-48 are products of same

gene.

• In intestine, mRNA undergoes editing, to

produce only B-48 protein.

• B-48 is named because it is only 40% of the size

of B-100.

• Apo-C-II:

• Activates lipoprotein lipase.

• Apo-E:

• Arginine rich protein.

• Present in chylomicrons, LDL & VLDL.

• Astrocytes also make apo-E.

• It is involved in transport of lipids in CNS.

• Apo-E has I,II,III & IV isoforms.

• Apo-E-IV is implecated in the development of

Alzheimer’s disease.

• Apo-E is also associated with glomerulopathy.

Chylomicrons

• Synthesis:

• Formed in intestinal mucosal cells, secreted

into the lymphatic system.

• Rich in triglycerides.

• When chylomicrons are synthesized by

intestinal mucosa, contain apo-B-48 & apo-A.

• Apo-C & apo-E are added from HDL in blood

during transport.

Structure of Chylomicrons

Metabolism of chylomicrons

• Site of metabolism:

• Adipose tissue & skeletal muscle.

• Half-life in blood is about 1 hour

• Lipoprotein lipase (LpL) is located at

endothelial layer of capillaries of adipose

tissue, muscles & heart.

• This enzyme is absent in liver.

• Apo-CII present in chylomicrons activates LpL.

• LpL hydrolyzes TGL present in chylomicrons

into fatty acids & glycerol.

• Muscles or adipose tissue cells takes up the

liberated fatty acids.

• Injection of heparin, LpL is released from

tissues & lipiemia is cleared.

• This is called as post-heparin lipolytic activity.

• Lack of C-II leads to decreased activity of LpL

& accumulation of chylomicrons & VLDL.

• Insulin increases LpL activity.

• Liver takes up chylomicron remnants:

• As TGL content is progressively decreased,

chylomicrons shink in size.

• These remnants containing apo-B-48 & apo-E

are taken up by hepatic cells by receptor

mediated endocytosis.

• Apo-E binds the hepatic receptors.

Chylomicrons Metabolism

Functions

• Transport of dietary TGL from intestine to

adipose tissue for storage.

• To muscle & heart for their energy needs.

Very low density lipoproteins

• Synthesis:

• Synthesized in the liver from glycerol & fatty

acids & incorporated into VLDL, along with

hepatic cholesterol, apo-B-100,C-II & E.

• Apo-B-100 is major lipoprotein in VLDL.

• Apo-E & C-II are obtained from HDL in plasma.

Metabolism of VLDL

• Half-life of VLDL is 1 to 3 hrs.

• In peripheral tissues, apo C-II activates LpL

which liberates fatty acids that are taken up

by adipose tissue & muscle.

• The remnant is called as IDL.

• IDL contains less of TAG & more of cholesterol.

• IDL further loses TAG, & converted to LDL.

• This conversion of VLDL to IDL & then to LDL is

referred to as lipoprotein cascade pathway

• IDL is taken up by hepatic receptors.

• Functions of VLDL.

• VLDL carries triglycerides (endogenous

triglycerides) from liver to peripheral tissues

for energy needs.

References

• Textbook of Biochemistry-U Satyanarayana

• Textbook of Biochemistry-DM Vasudevan

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