lipoproteins, 09
TRANSCRIPT
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Lipoprotein Metabolism
By
Amr S. Moustafa, M.D. ; Ph.D.
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Lipids compounds: Relatively water insoluble
Digestion: after Emulsifiction Absorption: as Micelles Blood transport: as Lipoproteins
Introduction
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Mixed Micelles
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Lipoprotein Structure
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Composition of
Lipoproteins
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Ultracentifugationof
Lipoproteins
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Lipoprotein Electrophoresis
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Secretion of Chylomicron from Intestine
Fat-Soluble vitamins
Microsomal TAG-transfer protein & assembly of CM in ER
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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
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Chylomicron Metabolism
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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
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Lipoprotein Lipase
Insulin: Synthesis & transfer
Isomer forms: Different Km(Adipose :Large, But, Heart: Small)
Highest concentration: Cardiac muscle
Plasma clearing effect: Heparin
CONT’D
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VLDL Metabolism
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Lipid-Transfer Protein
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LDL: Receptor-Mediated Endocytosis
Degraded
Recycled
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Athersclerotic plaque Formation
(SR-A)
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HDL Metabolism
(SR-B1)
VLDL CETP
Hepatic Lipase
Reverse Cholesterol Transport
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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
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Lipoprotein (a) or LP(a)
Factors Affecting Circulating Levels:
Genetic set-up
Sex (estrogen )
Diet (Trans FA )
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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
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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
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Steroid Hormones
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Steroid Hormones:Mechanism of Actions
Steroid/Thyroid Superfamily:Steroid HormonesThyroid HormonesCalcitriol (Vitamin D)Retinoic acid (Vitamin A)