LIPOPROTEIN METABOLISMDr. Ahmed al Taweel
ProblemWhat are lipids?
If so, how are these water insoluble molecules transported from one tissue to other through an aqueous environment?
Structure of triacylglycerol
GlycerolPalmitic acid
(hexadecanoic acid)
Phospholipid
Proteins have both hydrophobic and hydrophilic regions
Composition of aminoacids
Proteins are absolutely essential for forming the LP particlesLipoproteins
Core of TG and CESurface of phospholipids and some cholesterol
Apolipoproteins (regulators of LP metabolism)
CM, VLDL, IDL, LDL, HDL
Lipid metabolism occurs in three major areas
IntestineLiver
Extrahepatic tissues (Muscle and adipose tissue)
Enzymatic hydrolysis of TAG yields fatty acids and diacylglycerol, monoacylglycerol and free glycerol
Chylomicron assembly
Fatty acids, 2-MAGFatty acids, 2-MAG
ATP
ADP
Triacylglycerol
Apolipoproteins
ChylomicronsChylomicrons
lumen
intestinalepithelium
lymphatics
Protein
Triacylglycerol
Chylomicron assembly
Assembled in enterocyte Golgi/ERApolipoprotein (Apo) B organizes assembly
B48Requires
Phospholipids for surface
Chylomicrons are released from the intestine into the lymphatics, bypassing the liver
Lymphatics
(thoracic duct)Liver
Portal veinLungs
Systemic circulation
Questions
What are the lipids carried by CM?Where is CM formed?
What is the source for lipids in CM?
How does the CM release FFA?
What is the fate of the FFA and Glycerol?
Where is the LPL found?
What are the components of Remnant CM?
VLDL Assembly
Endogenous Lipid TransportLDL
Lipoprotein
lipaseCapillary wall
(endothelial surface)
Tissues
This animation shows how VLDL are metabolised once they enter the circulation from the liver
VLDL
B100
HDL
CII
E
CII
E
B100
Some LDL taken up
by liver (LDL receptors)Some LDL taken up by
other tissues (LDL receptors).LDL delivers cholesterol and
TAG to the extra hepatic tissues.
Having lost TAG to tissues LDL contains a large proportion of cholesterol/cholesterol esters
Regulation of Lipoprotein Lipase
Fed state -
LPL synthesis and activity (adipocytes)
Fasted/ -exercise
state
LPL synthesis and activity (muscle)
LPL synthesis and activity (skeletal and heart
muscle)LPL synthesis and activity (adipocytes)
Lactating -Mammary
gland
LPL activity
Endogenous Lipid TransportCholesterol uptake down regulates the cells own production of cholesterol and down regulates LDL receptor synthesis
HYPERLIPIDEMIA
Major CV risk factor - 25% of populationLDL, Total Choles., Total Choles./HDL, and 1/HDL all predict CVD
Reducing LDL with diet or drugs, prevents CVD, saves lives, time and money.Statins, fibrates, niacin, bile acid binding resins
Effect of ExerciseIncreases LPL activity in muscle.
Reduces TGL from the particle.Reduction in weight
Increases HDL
Effect of diet
Vegetarian diet – Cholesterol intake lessReduced Carbohydrate – VLDL TG Reduced
Reduced Fat – Reduces CM TG
Unsaturated fats ( Mono and Poly)- Reduction in Plasma cholesterol
Fiber – decreases cholesterol absorption
Postprandial Changes in Plasma Lipid Metabolism
Fat storage via LPL
Exchange of cholesterol for VLDL TG in HDL (CETP)LCAT activity = esterification of free cholesterol (HDL)
These postprandial changes are beneficial in maintaining whole body homeostasis of glycerides and cholesterolFat accumulation in adipose: High I/G (Fed)
FFAadipose
GlucoseInsulin
regulatedglucose
transport
CoA
Fatty acyl CoA
G3P
Triglycerides
TG/CEB48
CII
CIII
LPL
Capillary endothelium
insulin(+)
(+)
glut4
chylomicron