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By Dr. Elrasheed Eltaher Osman

Lipids Transport

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Dietary lipids and de novo synthesized lipid by adipose tissue and liver must be transported between various tissues and organs for utilization and storage.

Lipids are insoluble in waterThe problem arises of how to transport

this non-polar molecules in aqueous environment (the blood)

Introduction

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The problem solved through transporters called lipoproteins

They are amphipathic molecules (two phases polar and non-polar)

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Definition ClassesComponentsThe apolipoproteinsDescription of each classMetabolism

Lipoproteins

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These are complex lipids containing protein that transport lipid in the blood

They are amphipathic molecule

Definition of Lipoproteins

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Classify according to density into 1- chylomicron 2- very low density lipoprotein

(VLDL) 3- low density lipoprotein (LDL) 4- high density lipoprotein (HDL)

Classes of Lipoproteins

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Classify according to movement in eletrophoresis into

1- preβ-lipoprotein 2- β-lipoprotein 3- α-lipoprotein

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Consist of 1- lipids 2- proteins

Components of Lipoproteins

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This consist of 1- phospholipids 2- cholesterol 3- triacylglycerol 4- cholesteroylesterThe 2 above make outer membraneThe 2 below found inside making the

core

The Lipids of Lipoproteins

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Any Question

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Called apolipoproteinsThey are either integral part or

freely exchangeable proteinsNomenclature :using the letters A,

B, C, D, and E

The protein part Lipoproteins

Sub classes represent by latin number I, II, III and IV example apo A I, II, III, and IV apo C I, II and IIIApo B are two B100 and B48 (only 48% of the length of the first)

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Structural function apoB Receptor ligand apo EEnzyme activator apo A-IEnzyme inhibitor apo A-IITransporter apo D (lipid transfer

protein)

Functions of Apolipoproteins

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Include 1- Apo B100 2- Apo B48 3- Apo A- I.II.III and IV 4- Apo C- I.II and III 5- Apo E 6- Apo D

The Apo-lipoproteins

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Is the of longest polypeptide (4536 aa)Is glycoprotein Synthesize in the liver Found in VLDL, IDL and LDLIntegral protein play structural role as

well as receptor ligand for LDL receptor

Apolipoprotein B100 (Apo B100)

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Is about 48 % of the length of Apo B100

Contain 2153 amino acids

Synthesized by intestine Play structural role in chylomicron

Apolipoproteins B48 (ApoB48)

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Four types I, II, III and IVFound in HDL exchange with other

LPs (chylomicrons)Apo A-I is activator of enzyme LCAT

and ligand for HDL receptor

Apolipoproteins A (Apo A)Apo A-II is two identical polypeptides joint by disulfide bridge inhibitor of Apo A-I and LCATApo A-IV associated with formation of triacylglycerol –riched LP (chylomicron)

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Three types Apo C-I, II and IIISmall polypeptides freely transferable

between the different LPs Apo C-I found in VLDL, HDL and

chylomicron and is possiblr activator of LCAT

Apolipoproteins C (Apo C)

Apo C-II found in VLDL, HDL and chylomicron and is activator of lipoprotein lipaseApo C-III found in VLDL, HDL and chylomicron and is polymophous (due to sialic acid content) inhibitor of Apo C-II

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Found in VLDL, IDL, LDL, chylomircon and chylomicron reminants

Integral protein Is a ligand for chylomicron reminant

receptor in liver and LDL receptor in extra-hepatic tissue

Apolipoproteins E (Apo E)

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Is the large in size lest in density LPsSynthesized by intestineCarried the dietary lipid (triacylglycerol

and cholesterol)About 88% is triacylglycerolContains Apo B48, Apo A (I,II) and Apo C

Chylomicrom

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Found in certain HDL subfractionMay act as transporter Called lipid transfer protein

Apolipoproteins D (ApoD)

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Any Question

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ChylomicromVery low density lipoprotein (VLDL)Low density lipoprotein (LDL)High density lipoprotein (HDL)

Classes of lipoproteins

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LymphLymph EnterocyteEnterocyteIntestinalLumenIntestinalLumen

Chylomicron Formation

With

apoB48 CholesterylEster

Triglyceride

Phospholipid

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Secret in lymph goes to extrahepatic tissue (mainly adipose tissue)first where are metabolized

Metabolized by lipoprotein lipase to free fastty acid and chylomiron reminants

The chylomicron reminant goes to the liver where further metabolism occur

The chylomicron reminant entr the liver through receptor mediated pinocytosis

Chylomicrom

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Enzyme hydrolyzed tracylglycerol ninto fatty acids and glycerol

Found in blood vessels near extra-hepatic tissue mainly adipose tissue, heart and muscle

Lipoprotein lipase

It is partculate enzyme anchored to endothelium by( –ve proteoplycan chain of heparan sulfate),bond that is released by administration of heparin

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Synthesized and secreted by liverCarries lipid synthesized inside the liverCarried about 60 % triacylglycerolContain Apo B100, Apo C and Apo EMetabolyzed by lipoprotein lipase into

intermediate density lipoprotein IDL and LDL

Very low density lipoprotein (VLDL)

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Synthesized in the blood from other LPs mainly VLDL

Carried cholesterol to extra-hepatic tissue

Responsible for high blood cholesterol (bad cholesterol)

Contain Apo B100 and Apo E

Low density lipoprotein (LDL)

Most of LDL degraded in liver through Apo B100 and E receptorsA positive correlation exist between incidence of coronary atherosclerosis and plasma concentration of LDL

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Is synthesized and secreted from both liver and intestine

Contains Apo A, C and ENascent HDL from intestine lack Apo C and E

gain them when enter the blood from hepatic HDL

HDL act as repository for Apo C and E that required for metabolism of VLDL and chylomicrons

High density lipoprotein (HDL)

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The nascent HDL consists of discoid PL bi-layers containing Apo A and free cholesterol

When joins the enzyme LCAT (lecithin,cholesterol :acyltransferase) the free cholesterol esterified by one fatty of the PLs to form cholesteroylester and lysophospholipid

Cholesteroylester in non-polar moves to hydrophobic interior of the bi-layer where lysolecithin is transferred to plasma albumin

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LCAT continues forming CE that migrates to interior forming non-polar core the HDL become spherical in shape

LCAT system remove the unesterified cholesterol from lipoprotein and from tissue

HDL cycle account for transporting cholesterol from tissue to liver (good cholesterol) n process called reverse cholesterol transport

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