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

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Lipoprotein Metabolism

Presentation transcript:

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

Ultracentifugation of 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 Hyperlipoproteinemia Familial Lipoprotein lipase deficiency Type IIa Hyperlipoproteinemia Familial hypercholestrolemia Functional defect of LDL-receptor Type III Hyperlipoproteinemia Familial dysbetalipoproteinemia Apo E-2 isoform Hypercholestrolemia & atherosclerosis

Lipoprotein-related Diseases (B) Hypolipoproteinemia Congenital abetalipoproteinemia Defect in TAG-transfer protein Inability to load Apo B with lipids No CM or VLDL formation TAG accumulation: intestine & liver (C) Fatty Liver (hepatic steatosis) Decreased secretion of VLDL Obesity, DM, Chronic alcoholism

Steroid Hormones

Steroid Hormones: Mechanism of Actions Steroid/Thyroid Superfamily: Steroid Hormones Thyroid Hormones Calcitriol (Vitamin D) Retinoic acid (Vitamin A)