LIPOPROTEINS

Objectives
 Structure & composition
 Classification
 Metabolism
 Associated disorders
 Structure & composition
These are macromolecules made up mainly of lipids & proteins

Structurally, the contain;

An inner nonpolar core made of
TAG, cholesterol & esters.
An amphipathic surface layer
made of Cholesterol & phospholipid

NB
It has an apolipoprotein (apoprotein) which
is the protein moiety.
Structure of lipoproteins
Apolipoprotein

 Surface proteins present on lipoproteins.

Play vital role in

a. Providing structural stability to lipoproteins.
b. Acting as Ligands in lipoprotein-receptor interactions.
c. Cofactors in enzymatic processes that regulate lipoprotein
metabolism.

Classified into; 1.Integral proteins- Apo A & B

2.Peripheral proteins- Apo C & E
Roles of lipoproteins

Transportation of lipids absorbed from the diet & those synthesized by

the liver or adipose tissue for energy production or storage.

Question
Briefly explain why lipoproteins are vital in the transportation lipids
between cells & organs in the body?
Classification of lipoproteins

There are four major classes of lipoproteins xterised by three factors;

The density
Electrophoretic mobility &
Nature of the Apoprotein

These classes are; Note

 The Chylomicrons (CMs) are also
1. Very low density lipoproteins (VLDL) Lipoproteins but with very high Lipid
2. Intermediate density lipoproteins (IDL) content (≈99%).

3. Low-density lipoproteins (LDL),  VLDL are synthesized from the liver for
the export of triacylglycerol, IDL are
4. High-density lipoproteins (HDL), product of VLDL catabolism and LDL are
final product of the catabolism.
 Classification contꞌd

Lipoproteins with high lipid content will have low density, larger size & so float on centrifugation.
Those with high protein content sediment easily, have compact size and have a high density.

As the lipid content increases, density decreases and size increases, that is why Chylomicrons are least dense but
biggest in size, while HDL are rich in proteins , hence most dense but smallest in size.
Based on electrophoretic mobilities
 HDL are -α , VLDL pre- β, LDL-β , & IDL are broad beta lipoproteins.

 Free fatty acid & albumin complex although not a lipoprotein is an

important lipid fraction in serum & is the fastest moving fraction.

 Chylomicrons remain at the origin since they have more lipid

content.

 VLDLs with less protein content than LDL move faster than LDL, this
is due to nature of apoprotein present.
Based on nature of Apo- protein content
 One or more apolipoproteins (proteins or polypeptides) are
present in each lipoprotein.
 The major apolipoproteins of HDL (α-lipoprotein) are designated
A.
 The main apolipoprotein of LDL (β -lipoprotein) is apolipoprotein
B (B-100), which is found also in VLDL.
 Chylomicons contain a truncated form of apo B (B-48) that is
synthesized in the intestine, while B-100 is synthesized in the
liver.
 Apo E is found in VLDL, HDL, Chylomicons, and chylomicron
remnants.
Metabolism of lipoproteins

Guiding Questions.
1. Using Kenneth R. Feingold, MD (2021), describe the metabolism of;
a) Chylomicrons
b) VLDL
c) LDL
d) HDL
2. Briefly describe the Clinical Significance of lipoprotein metabolism.
 Metabolism of lipoproteins

As in main lipids, this takes place in three major areas;

1. Intestine

2. Liver

3. Extrahepatic tissues (Muscle and adipose tissue)

Note:

Enzymatic hydrolysis of TAG yields fatty acids and diacylglycerol,

monoacylglycerol and free glycerol

O O OH OH O OH OH OH OH
O O OH OH O OH OH OH OH
O O O O O O

CH3 CH3 CH3

CH3 CH3 CH3 CH3 CH3 CH3
Metabolism of Chylomicron

Driving questions
1. What are the lipids carried by CM?
2. Where is CM formed?
3. What is the source for lipids in CM?
4. How does the CM release FFA?
5. What is the fate of the FFA and Glycerol?
6. Where is the LPL found?
7. What are the components of Remnant CM?
 Chylomicron assembly
Fatty acids, 2-MAG lumen
Note:
 Takes place in the enterocytes of the Golgi/ER.
 Organized by Apo B (B48).
 Requires phospholipids at the surface.

Fatty acids, 2-MAG

Protein ATP
ADP intestinal
Triacylglycerol epithelium

Apolipoproteins

Chylomicrons

Triacylglycerol Chylomicrons lymphatics

Note:
TG composition closely resembles the dietary
intake.

 Chylomicrons are released from the intestine

into the lymphatics, bypassing the liver.

 Picks apo A, C & E from plasma.

Summary
Lungs

Lymphatics
(thoracic duct)

Liver

Portal vein

Systemic
circulation
Metabolism of VLDL

Driving questions
1. Where is VLDL formed?
2. What are the lipids Carried by VLDL?
3. Which lipid is delivered by VLDL?
4. What is the mechanism of FFA release from
VLDL?
5. What is the fate of Remnant VLDL?
6. What are the lipids present in excess when
VLDL becomes VLDLR?
VLDL Assembly Plasma
Dietary Carbohydrate
LIVER

glucose pyruvate Acetyl CoA

B48 LDL receptor Acetyl CoA

E mitochondria
TG/CE
TG
CMr Cholesterol
cholesterol (endogenous)
B100
(exogenous)
CE/TG VLDL
FFA FFA TG

VLDL
Endogenous Lipid Transport
This animation shows how VLDL are
metabolised once they enter the circulation
from the liver

B100 Tissues

B100
VLDL Lipoprotein
LDL lipase
Some LDL taken up E CII
by liver (LDL receptors)
Having lost TAG to
tissues LDL contains a
large proportion of
cholesterol/cholesterol
esters
Capillary wall
(endothelial surface)
Some LDL taken up by
other tissues (LDL receptors).
LDL delivers cholesterol and
TAG to the extra hepatic tissues.
 LPL “Metabolic Gatekeeper”?

 Disorder: LPL deficiency Functions

(chylomicronaemia)
Results into;  Endocytosis of LDL and other LP
 Massive accumulation of  Release free cholesterol into liver
chylomicron -TG in plasma
 Cannot clear TG normally o Incorporate into plasma membrane
 Normal fat storage and body o Inhibit new LDL receptors
weight o Inhibit cholesterol synthesis
o Promote ACAT activity (FC -> CE)
 Regulated by SREBP, monitors free
cholesterol
SREBP, Sterol regulatory element binding proteins
ACAT, Acyl-coenzyme A (CoA):cholesterol acyltransferase
 Regulation of Lipoprotein Lipase
Fed state - LPL synthesis and activity (adipocytes)

LPL synthesis and activity (skeletal and heart

muscle)
Fasted/ - LPL synthesis and activity (adipocytes)
exercise
LPL synthesis and activity (muscle)
state
Lactating -
Mammary LPL activity
gland

Note:
Cholesterol uptake down regulates the cells own production of cholesterol and down
regulates LDL receptor synthesis
Questions
How is LDL formed?
What is IDL?
What is HTGL?
How is CE transferred from HDL to IDL?
What is CETP?
 CETP exchanges cholesterol esters in HDLs for triglycerides in B100 LPs

VLDL
CE

CETP
FFA
LPL TG

Liver IDL TG
(LDL receptor) HDL
CETP
CE

FFA TG
LPL CETP
Liver
CE
(LDL receptor)
LDL
 Dietary Regulation of Lipoprotein
Synthesis
Chylomicron Synthesis VLDL Synthesis (Liver)

Chylomicron VLDL (+)

High CARB FA/TG
Insulin

(+)
Acetyl CoA
Dietary Fat

Intestinal Epithelium
(+)
Glucose
  Disorder: 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.
Disorder:
Atherosclerosis
Atherosclerosis

ACS: Acute coronary syndrome

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

Lecithin: Cholesterol Acyltransferase

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

(+)
B48 insulin
CII
LPL
TG/CE FFA-albumin (oxidation)
CIII
Glucagon

chylomicron FFA Glucose

glut4
(+) Insulin
regulated
glucose
CoA transport
G3P
Fatty acyl CoA

Triglycerides
adipose
END