Lipoproteins Metabolism. Lipid compounds are relatively water insoluble. Therefore, they are...
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Lipoproteins Metabolism. Lipid compounds are relatively water insoluble. Therefore, they are transported in plasma (aqueous) as lipoproteins Introduction
Lipid compounds are relatively water insoluble. Therefore, they
are transported in plasma (aqueous) as lipoproteins
Introduction
Slide 3
Lipoproteins and Related Clinical Problems Atherosclerosis
Atherosclerosis Hypertension Hypertension Coronary heart diseases
Coronary heart diseases Lipoproteinemias (hypo- and hyper-)
Lipoproteinemias (hypo- and hyper-) Fatty liver Fatty liver
Slide 4
Lipoprotein Structure Protein part: Apoproteins or
apolipoproteins structuraltransferred Apoproteins proteins may be
structural or transferred Lipid part: Each lipoprotein contains
different types of lipids in various combinations Type of lipids
Type of lipids in a lipoprotein is governed according to the type
of lipoprotein
Apolipoproteins (Apoproteins) Five major classes (A-E) divided
by structure & function Each class has subclasses as Apo A, Apo
CII Functions: structural proteins Some are required as structural
proteins (i.e. they are essential structural components of the
lipoprotein particles & can not be produced without them)
activators Some are activators for enzymes of lipoprotein
metabolism recognition sites Some are recognition sites for
cell-surface receptors
Slide 7
Types of Lipoproteins Types of lipoproteins are different in
lipid & protein composition & therefore, they differ in:
Size & density - Size & density Electrophoretic mobility -
Electrophoretic mobility
Slide 8
Types and CompositionofLipoproteins Chylomicrons Very low
density Lipoprotein (VLDL) Low density Lipoprotein (LDL) High
density Lipoprotein (HDL)
Slide 9
Size & Density ofLipoproteins
Slide 10
Lipoprotein Electrophoresis
Slide 11
Plasma Lipoproteins For triacylglycerol transport (TG-rich):
For triacylglycerol transport (TG-rich): Chylomicronsdietary -
Chylomicrons: TG of dietary origin VLDLendogenous - VLDL: TG of
endogenous (hepatic) synthesis For cholesterol transport
(cholesterol-rich): For cholesterol transport (cholesterol-rich):
LDL - LDL: Mainly free cholesterol HDL - HDL: Mainly esterified
cholesterol
Slide 12
Chylomicrons Synthesis Synthesis: in intestinal mucosal cells
Function Function: dietary lipids Transport dietary lipids from GIT
to tissues (& liver). Responsible for physiological milky
appearance of plasma (up to 2 hours after meal) Structure
Structure: density Lowest density size Largest size lipids proteins
Highest % of lipids and lowest % proteins triacylglyceroldietary
Highest triacylglycerol (dietary origin)
Slide 13
Apo E mediates uptake Type I hyperlipoprotemia Chylomicrons
metabolism
Slide 14
Lipoprotein Lipase most tissue Extracellular enzyme anchored by
heparan sulphate to the capillary walls of most tissue especially
those of adipose tissue, cardiac & skeletal muscles not BUT:
Adult liver does not have this enzyme Its synthesis & transfer
to luminal surface of the capillary is stimulated by insulin (in
fed state) Activated by apoC-II Function of lipoprotein lipase
Lipoprotein lipase hydrolyses circulating TG in chylomicrons to
fatty acids & glycerol Fatty acids Fatty acids are stored (in
adipose) or used for energy (in muscles) Glycerol Glycerol is
transferred to the liver (to be used for glycolysis,
gluconeogenesis or lipid synthesis) Deficiency of lipoprotein
lipase (or apo CII) : type 1 hyperlipoproteinemia (familial
lipoprotein lipase deficiency) causes type 1 hyperlipoproteinemia
(familial lipoprotein lipase deficiency) hypertriglyceridemia
accumulation of chylomicrons in plasma (hypertriglyceridemia)
Slide 15
Very Low Density Lipoproteins (VLDL) - Synthesisliver -
Synthesis: in the liver Structuretriglycerides(TG) - Structure:
composed predominantly of triglycerides (TG) Function : - Function
: is to carry lipids (mainly TG) from the liver to tissues.
lipoprotein lipase In peripheral tissues, TG are degraded by
lipoprotein lipase to FA & glycerol. Fatty liver (hepatic
steatosis) Occurs when TG synthesis in liver is more than VLDL
secretion As in cases of As in cases of: - Obesity - Uncontrolled
DM - Chronic ethanol ingestion
Slide 16
Metabolism of VLDL
Slide 17
Low Density Lipoproteins (LDL) LDL LDL is produced in the
circulation as the end product of VLDLs Compared to VLDLs: apo
B-100 It contains only apo B-100 Smaller size & more dense
(less lipids) Lipid contents: Less triglycerides (TG) More
cholesterol (C) & cholesterol ester (CE) Function of LDL LDL
transport cholesterol from liver to peripheral tissues LDL
receptor-mediated endocytosis recognized Uptake of LDL at tissue
level by LDL receptor-mediated endocytosis recognized by apo
B-100
Slide 18
Receptor-Mediated Endocytosis LDL (through apo 100), LDL
receptors 1- LDL (through apo 100), binds to LDL receptors in
peripheral tissues forming a complex Internalization 2-
Internalization of the complex by endocytosis to inside cells.
Release 3- Release of cholesterol inside the cells for:
Utilization, storage (as cholesterol ester) or excretion 4-
Degradation of LDL: into amino acids, PL & FAs 5- Degradation
or recycling of receptor Deficiency of functional LDL receptors:
Causes elevation of LDL in blood (& therefore blood cholesterol
is elevated) Type II hyperlipidemia (familial
hypercholesterolemia)
Slide 19
LDL: Receptor-mediated endocytosis
Slide 20
LDL Receptor-Mediated Endocytosis: Regulation Cholesterol
derived from LDL causes: 1-Decrease de novo synthesis of
cholesterol 1- Decrease de novo synthesis of cholesterol (by
inhibition of HMG CoA reductase) 2- Inhibition of LDL receptor
synthesis at gene level thus, limiting further entry of LDL
cholesterol into cells. 3- 3- In case cholesterol is not used
immediately: Cholesterol is esterified to cholesterol esters (CE)
by: acyl CoA: cholesterol acyltransferace (ACAT). Cholesterol
esters can be stored in cells. ACAT is enhanced in cases of
increased intracellular cholesterol.
Slide 21
LDL-C = Total cholesterol [ HDL-C + TG/2.2 ] in case of mmol/L
or 5 in case of mg/dL Low Density Lipoprotein Cholesterol (LDL-C)
calculation
Slide 22
Slide 23
Categories of Risk for LDL Cholesterol Goals LDL goal mg/dL
< 100