20

Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Embed Size (px)

Citation preview

Page 1: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D
Page 2: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Lipoprotein Metabolism

By

Amr S. Moustafa, M.D.; Ph.D.

Page 3: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Lipid compounds: Relatively water insoluble

Therefore, they are transported in plasma (aqueous) as Lipoproteins

Introduction

Page 4: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Lipoproteins and Related Clinical Problems

• Atherosclerosis and hypertension • Coronary heart diseases

• Lipoproteinemias (hypo- and hyper-)

• Fatty liver

Page 5: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Lipoprotein Structure

Protein part: Apoproteins or apolipoproteinsAbbreviations: Apo-A, B, C, D, EFunctions:

Structural and transport functionEnzymatic functionLigands for receptors

Lipid part:• According to the type of lipoproteins• Different lipid components in various combinations

Page 6: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Lipoprotein Structure

Spherical molecules of lipids and proteins (apoproteins)

Outer coat: Apoproteins Phospholipids Cholesterol

Inner core: TG Cholesterol ester

Page 7: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Types of Lipoproteins

• Why do we have different types of lipoproteins?

They differ in lipid and protein composition

and therefore, they differ in

Size and density

Electrophoretic mobility

Page 8: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Types andComposition

ofLipoproteins

Chylomicrons

Very low densityLipoprotein (VLDL)

Low densityLipoprotein (LDL)

High density Lipoprotein (HDL)

Page 9: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Ultracentrifugationof

Lipoproteins

Page 10: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Lipoprotein Electrophoresis

Page 11: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Plasma Lipoproteins

For triacylglycerol transport (TG-rich):Chylomicrons: TG of dietary originVLDL: TG of endogenous (hepatic) synthesis

For cholesterol transport (cholesterol-rich): LDL: Mainly free cholesterol HDL: Mainly esterified cholesterol

Page 12: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Chylomicrons• Assembled in intestinal mucosal cells

• Lowest density

• Largest size

• Highest % of lipids and lowest % proteins

• Highest triacylglycerol (dietary origin)

• Carry dietary lipids to peripheral tissues

• Responsible for physiological milky appearance of plasma (up to 2 hours after meal)

Page 13: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Very Low Density Lipoproteins

VLDLs• Assembled in liver

• High triacylglycerol (hepatic origin)

• Carry lipids from liver to peripheral tissues

• Nascent VLDL: contains Apo B-100

• Mature VLDL: Apo B-100 plus

Apo C-II and Apo E

(from HDL)

Page 14: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Metabolism of VLDLs• Assembled and secreted by liver

• Mature VLDLs in blood

• Modifications of circulating VLDLs

• End products: IDL and LDL

• Related diseases:

Hypolipoproteinemia: Abetalipoproteinemia

Hyperlipoproteinemias:

Type I hyperlipoproteinemia

Familial type III hyperlipoproteinemia

Page 15: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

VLDL Metabolism

Page 16: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Metabolism of VLDLs: Mature VLDLs

• Assembled and secreted by liver directly into blood as nascent form

• Mature VLDLs: contain Apo B-100 plus Apo C-II and Apo E. ApoC-II is required for activation of lipoprotein lipase

• Lipoprotein lipase is required to degrade TG into glycerol and fatty acids

Page 17: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Modifications of Circulating VLDLs

• As TG is degraded, VLDLs become

Smaller in size

More dense

Apo C back to HDL

Exchange of TG with cholesterol ester (HDL)

by cholesterol ester transfer protein

• Production of LDL in plasma

VLDL IDL (returns Apo E to HDL) LDL

Page 18: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

Lipid-Transfer Protein

Page 19: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

VLDLs-Related DiseasesHypolipoproteinemia

AbetalipoproteinemiaDefect in TG-transfer proteinApo B-100 cannot be loaded with lipidAccumulation of TG in liver

Fatty Liver (hepatic steatosis)Imbalance between hepatic synthesis of TG and secretion of VLDLs. Accumulation of TG in liver

Page 20: Lipoprotein Metabolism By Amr S. Moustafa, M.D.; Ph.D

VLDLs-Related DiseasesHyperlipoproteinemia

Type I HyperlipoproteinemiaFamilial Lipoprotein lipase deficiencyor Apo C-II deficiencyUsually associated with acute abdomendue to acute pancreatitis

Type III HyperlipoproteinemiaFamilial dysbetalipoproteinemiaApo E deficiencyHypercholesterolemia and atherosclerosis