Biochemistry ІI

Lipid Transport & Storage

Dr. Ihab Abdel Moneam, PhD Lec. 12

Intended Learning Outcomes:
 By the end of this lecture, the students will know:
- Structure of lipoproteins
- Types of lipoproteins
- Metabolism of lipoproteins
- Storage & hydrolysis of triacylglycerol
 Lipid Transport & Storage
Introduction :
 Lipids transfer from the intestine or liver to other
tissues through blood.
 Lipids which are water-insoluble, can transport in
blood as lipoproteins (lipid carriers).
 Lipoproteins Consist of a Nonpolar Core & a Single
Layer of Amphipathic Lipids.
(NOTE: Lipid is mobilized from adipose tissue as free fatty
acids bound to serum albumin).
 Lipoproteins:
Structure:
a- Lipids (phospholipids, TG,
cholesterol ester, cholesterol
free fatty acids..etc).
b- Proteins (Apoproteins)
(Note: FFA is metabolically the most active of the plasma lipids).
Functions of Apoproteins:
1- a part(hydrophilic)of the structure of the lipoprotein
2- as enzyme cofactors
3- as ligands for interaction with their receptors in
tissues.
 Lipoproteins:
Types:
1- Chylomicrons Density
2- Very Low Density Liporoteins (VLDL Increases
or pre-β-lipoproteins)
3- Low Density Lipoproteins (LDL or β-lipoproteins)
4- High Density Lipoproteins (HDL or α-lipoproteins)
(Note: plasma lipoproteins can be separated by electrophoresis)

Metabolism of lipoproteins:
1- Chylomicron:
- Site of synthesis: intestinal cells
Metabolism of lipoproteins:
1- Chylomicron:
- Structure:
a- Lipids: mainly TG + phospholipids + cholesteryl esters
+ cholesterol + fat soluble vitamins.
b- Apoproteins: apo B48 and receives apo C-II &
apo-E from circulating HDL.
- Function: Transport dietary lipids (mainly TG) from
intestine into blood or peripheral tissues.
- Catabolism: TG are hydrolyzed by lipoprotein lipase
(activated by apoCII). the remaining parts are chylomicron
remnants (without apo CII) , which are taken up by
the liver through apo E receptors.
Metabolism of lipoproteins:
2- VLDL:
- Site of synthesis: liver.
- Structure:
a- Lipids: mainly TG + phospholipids + cholesterol
b- Apoproteins: apo B100 and receives apo C-II &
apo-E from HDL.
- Function: Transport lipids (mainly TG) from liver to
extrahepatic tissues.
- Catabolism: TG are hydrolyzed by lipoprotein lipase
(activated by apo CII). The remaining parts are IDL, are
converted into LDL by transferring apo CII & E to HDL.
 MetabolismofofChylomicron:
Metabolism Chylomicron

Metabolism of LDL
 NOTES :

 TG is the predominant lipid in chylomicron & VLDL.

 Apo B48 of chylomicron & apo B100 of VLDL are
integral apoproteins whereas, apo CII & apo E of both
are peripheral apoproteins.
 Apo E is a ligand for chylomicron remnant receptor in
liver.
 Nascent chylomicron &VLDL doesn't have apo C or
apo E.
 Chylomicron & VLDL are catabolized rapidly mainly in
Adipose tissue, heart & muscle by lipoprotein lipase.
 The liver does not metabolize native chylomicrons or
VLDL.
 NOTES :
Hepatic VLDL secretion is related to diet & hormones:
 Sources of fatty acids in the liver:
1- Acetyl CoA ( from carbohydrate during the fed state)
2- Uptake of FFA from circulation (during starvation
, high-fat diet or diabetes mellitus)
 Synthesis of VLDL occurs in ER which requires
microsomal TG transfer protein (MTP).
 Factor stimulating the formation of TG & secretion of
VLDL:
1- The fed state (high-carbohydrate or fat diet).
2- insulin & glucagon 3- ethanol ingestion ( lipogenesis)
Metabolism of lipoproteins:

3- LDL: (final stage of VLDL catabolism)

- Site of synthesis: circulation from VLDL
- Structure:
a- Lipids: cholesterol + cholesteryl esters + phospholipids
b- Apoproteins: apo B100.
- Function: provides cholesterol to peripheral tissues.
- Catabolism: LDL Apo B100 are recognized by LDL
(or apo B100) receptors in tissues via the binding
between them. Then, LDL undergoes endocytosis.
 NOTES :

 Cholesterol & phospholipids are the predominant lipids

in LDL & HDL.
 LDL is the primary cause of atherosclerosis because:
 Oxidized LDL adheres to the wall of blood vessels
then, oxidized LDL can be taken up by Binding to
Scavenger Receptors Class A (SR-A) of macrophages

forming foam cells

that is participates in atherosclerotic plaque.
SO, LDL is a bad cholesterol carrier .
Metabolism of lipoproteins:
4- HDL:
- Site of synthesis: Liver & intestines
- Structure:
a- Lipids: cholesterol ( free & esterified )
+ phospholipids (mainly lecithin).
b- Apoproteins: apo A1 (activates LCAT & as ligand
for HDL receptor), apo CII (activates lipoprotein lipase).
& apo E (as a ligand of apo E receptor for endocytosis).
- Function: - Act as a repository for apo C & apo E to
chylomicron & VLDL.
- Remove cholesterol from peripheral tissues to liver
in the form of cholesterol ester by LCAT.
4- HDL:
- Catabolism: Via SR-B1 (HDL receptors), nascent HDL
accept nonesterified cholesterol from peripheral tissues
in the form of cholesterol ester (by LCAT) generating:
HDL3 More esterified
cholesterol
HDL2
-Then, HDL is taken up by liver (via SR-B1) where
cholesterol ester is released and excreted in bile.
- This process is reverse cholesterol transport which
Occurs by the following mechanisms:
1- ATP-binding cassette transporters A1 (ABCA1)
2- SR-B1 3- ABCG1
 NOTES :
 HDL is involved in cholesterol transport & in VLDL
and chylomicron metabolism.
 Generally, apo C & E are synthesized by liver.
 Nascent HDL consists of discoidal phospholipid bilayer
containing apo A-1 & free cholesterol.
 HDL is a good cholesterol carrier.
The liver plays a role in lipid transport and metabolism:
due to:
1- Digestion & absorption of lipids by bile
2- Synthesis & oxidation of fatty acids 3- ketogenesis
4- Synthesis & metabolism of lipoproteins.
Disorders (abnormalities) of lipoprotein metabolism:
1- Hyperlipoproteinemia:
a) Hypertriacylglycerolemia: due to
- Diabetes mellitus (causes FFA & underutilization
of VLDL& chylomicron). - Overproduction of VLDL
b) Familial Hypercholesterolemia:
- Due to deficiency of LDL receptor.
- Causes premature atherosclerosis.
2- Hypolipoproteinemia:
a) Abetalipoproteinemia: due to
- Absence of lipoproteins containing apo B.
NOTE:
- LCAT deficiency & obstructive jaundice may Nascent HDL.
 Lipid storage & hydrolysis
 Body lipids are 4 types: tissues lipid, adipose tissues
(as fat droplets) & Plasma lipoproteins
 Adipose tissues store lipids in the form of TG
(from absorbed fat or carbohydrates) through lipogenesis.
 Regulation of lipogenesis:
1-Hormonal action:
- insulin: stimulates lipogenesis
- Glucagon & epinephrine: inhibit lipogenesis
2- Its substrates: activates lipogenesis
- FFA pool ( due to high fat or carbohydrate diet).
- Synthesis of glycerol-3-phosphate.
 Lipid storage & hydrolysis
Lipolysis:
Definition: hydrolysis of TG in adipose tissues into glycerol
& free fatty acids by a number of lipase enzymes,
1- hormone-sensitive triacylglycerol lipase
2- Diacylglycerol lipase 3- Monoacylglycerol lipase
Fate of products of lipolysis:
- Fatty acids: oxidation to produce energy or resterification.
- Glycerol: may diffuse to blood & then to some tissues
(e.g. liver & kidney) to give:
1- Glucose by gluconeogenesis 2- pyruvate by glycolysis
3- Glycerol-3-ph by glycerol kinase.
 Lipid storage & hydrolysis
Regulation of lipolysis:
 The key enzyme controlling lipolysis is:
hormones-sensitive lipase. Phosphorylated form (Active)
Dephosphorylated form(inctive)
- Hormonal action:
Glucagon: stimulates lipolysis HOW?
+
Glucagon adenylyl cyclase cAMP + protein kinase
active hormone sensitive lipase (phosphorylated)
Insulin: inhibits lipolysis
- Insulin + protein phosphatase inactive hormonal
sensitive lipase
+
- Insulin phophodiesterases (destroy cAMP)
 Lipid storage & hydrolysis
Other hormones & compounds affect lipolysis:
 Epinephrine, norepinephrine, ACTH, TSH, GH
& ADH Promote lipolysis via + adenylyl cyclase.
 Prostaglandin E1 & nicotinic acid (vitamin B3)
inhibit lipolysis by  adenylyl cyclase.
 Methyl xanthines (e.g. caffeine & theophylline) have
lipolytic effect by  phosphodiesterase.

NOTES :
- Uptake of glucose into Adipose tissues & muscle via GLUT4.
- Perilipin Regulates the Balance between Triacylglycerol
Storage and Lipolysis in Adipocytes.