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LIPOPROTEIN METABOLISMDr. Ahmed al Taweel

Problem
What are lipids?

If so, how are these water insoluble molecules transported from one tissue to other through an aqueous environment?

Structure of triacylglycerol

Glycerol
Palmitic acid
(hexadecanoic acid)

Phospholipid

Lipids




Proteins have both hydrophobic and hydrophilic regions

Composition of aminoacids

Proteins are absolutely essential for forming the LP particles

Lipoproteins

Core of TG and CE
Surface of phospholipids and some cholesterol
Apolipoproteins (regulators of LP metabolism)
CM, VLDL, IDL, LDL, HDL


Lipids

Lipid metabolism occurs in three major areas

Intestine
Liver
Extrahepatic tissues (Muscle and adipose tissue)


Enzymatic hydrolysis of TAG yields fatty acids and diacylglycerol, monoacylglycerol and free glycerol

Chylomicron assembly

Fatty acids, 2-MAG
Fatty acids, 2-MAG

ATP
ADP
Triacylglycerol

Apolipoproteins

Chylomicrons
Chylomicrons

lumen

intestinal
epithelium
lymphatics

Protein


Triacylglycerol

Chylomicron assembly

Assembled in enterocyte Golgi/ER

Apolipoprotein (Apo) B organizes assembly

B48
Requires
Phospholipids for surface

Chylomicrons are released from the intestine into the lymphatics, bypassing the liver

Lipids

Lymphatics

(thoracic duct)

Liver

Portal vein
Lungs
Systemic circulation



Lipids

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 Transport

LDL

Lipoprotein

lipase
Capillary wall
(endothelial surface)
Tissues


This animation shows how VLDL are metabolised once they enter the circulation from the liver
VLDL
B100
HDL
CII
E
Lipids


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 Transport


Cholesterol uptake down regulates the cells own production of cholesterol and down regulates LDL receptor synthesis

HYPERLIPIDEMIA

Major CV risk factor - 25% of population

LDL, 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 Exercise

Increases LPL activity in muscle.

Reduces TGL from the particle.
Reduction in weight
Increases HDL

Effect of diet

Vegetarian diet – Cholesterol intake less
Reduced 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 cholesterol

Fat accumulation in adipose: High I/G (Fed)

FFA

adipose

Glucose

Insulin

regulated
glucose
transport
CoA


Fatty acyl CoA
G3P

Triglycerides

TG/CE
B48
CII
CIII

LPL

Capillary endothelium

insulin

(+)
(+)
glut4
chylomicron

FFA-albumin (oxidation)

Glucagon



رفعت المحاضرة من قبل: Sultan Alsaffar
المشاهدات: لقد قام 11 عضواً و 177 زائراً بقراءة هذه المحاضرة








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