Lipoprotein Metabolism

By

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

Lipids compounds: Relatively water insoluble

Digestion: after Emulsifiction Absorption: as Micelles Blood transport: as Lipoproteins

Introduction

Mixed Micelles

Lipoprotein Structure

Composition of

Lipoproteins

Ultracentifugationof

Lipoproteins

Lipoprotein Electrophoresis

Secretion of Chylomicron from Intestine

Fat-Soluble vitamins

Microsomal TAG-transfer protein & assembly of CM in ER

Intestinal Apo B-48

Post-transcriptional editing of Apo B gene

Deamination of cytosine to uracil

Insertion of stop codon (Nonsense)

Translation of only 48% of Apo B gene

Chylomicron Metabolism

Lipoprotein Lipase

Synthesis: Adipocytes and muscle cells

Extracellular enzymes (isomer forms)

Anchored by HS to capillary walls

Most tissues, but not adult liver

Activated by: Apo C-II & Heparin

Deficiency: Type 1 hyperlipoproteinemia

Lipoprotein Lipase

Insulin: Synthesis & transfer

Isomer forms: Different Km(Adipose :Large, But, Heart: Small)

Highest concentration: Cardiac muscle

Plasma clearing effect: Heparin

CONT’D

VLDL Metabolism

Lipid-Transfer Protein

LDL: Receptor-Mediated Endocytosis

Degraded

Recycled

Athersclerotic plaque Formation

(SR-A)

HDL Metabolism

(SR-B1)

VLDL CETP

Hepatic Lipase

Reverse Cholesterol Transport

Lipoprotein (a) or LP(a)

LP(a): ~ identical to LDL

Apo(a): Additional apoprotein

covalently-linked to apo B-100

Homologous to plasminogen

Interferes with breakdown of blood clots

& triggers heart attack

LP(a) plasma level: Risk for CHD

Lipoprotein (a) or LP(a)

Factors Affecting Circulating Levels:

Genetic set-up

Sex (estrogen )

Diet (Trans FA )

Lipoprotein-related Diseases(A) Hyperlipoproteinemia

Type I HyperlipoproteinemiaFamilial Lipoprotein lipase deficiency

Type IIa HyperlipoproteinemiaFamilial hypercholestrolemiaFunctional defect of LDL-receptor

Type III HyperlipoproteinemiaFamilial dysbetalipoproteinemiaApo E-2 isoformHypercholestrolemia & atherosclerosis

Lipoprotein-related Diseases(B) Hypolipoproteinemia

Congenital abetalipoproteinemiaDefect in TAG-transfer proteinInability to load Apo B with lipidsNo CM or VLDL formationTAG accumulation: intestine & liver

(C) Fatty Liver (hepatic steatosis)Decreased secretion of VLDLObesity, DM, Chronic alcoholism

Steroid Hormones

Steroid Hormones:Mechanism of Actions

Steroid/Thyroid Superfamily:Steroid HormonesThyroid HormonesCalcitriol (Vitamin D)Retinoic acid (Vitamin A)