Describe the endogenous pathway of lipoprotein metabolism

Lipoprotein metabolism
A. Describe the exogenous pathway of lipoprotein metabolism [6 marks]
B. Briefly describe the LDL receptor mediated endocytosis [4 marks]

Exogenous pathway Endogenous pathway

1. Dietary fat and cholesterol enter the
intestine
2. These absorbed fat and cholesterol
bind to form chylomicrons in the
intestinal cell
3. The cyclomicrons then travel into vein
and into bloodstream to peripheral
tissue
4. In the peripheral tissue, chylomicron
release their fat when found
lipoprotein lipse
5. This allow fat to be absorb as fatty
acid and glycerol
6. After unloading their fat, chylomicrons
become smaller and become
chylomicrons remnant
7. Chyclomicrons remnant then travel
into liver and removed by binding of
ApoE to their remnant receptor
1. Fat and cholesterol arriving the liver is
repackage int VLDL
2. VLDL enter bloodstream between
meal and ravel to peripheral tissue
3. VLDL meats lipoprotein and release
their fat into fatty acid and glycerol
4. After VLDL unloaded, it become
smaller and form IDL
5. IDL can be convert into LDL which
carry cholesterol from the liver to
various cell in the body
6. LDL binds to the LDL receptor release
cholesterol in the liver

LDL receptor mediated endocytosis

1. LDL binds to LDL receptors on the cell surface
2. The LDL-receptor complex triggers the formation of clathrin-coated vesicle that buds
off from the plasma membrane and enter the cytoplasm
3. The vesicle fuses with an early endosome. The low pH causes the LDL to dissociate
from the receptor
4. The LDL receptor is sorted into another vesicle that returns to the plasma membrane,
were it can bind more LDL molecules
5. The LDL transferred to a lysosome that breakdown the LDL into cholesterol and amino
acids

Synthesis, regulation and excretion of cholesterol

a) describe 4 mechanism of cholesterol regulation

b) rate limiting factor of cholesterol synthesis

B)reverse cholesterol transport

Synthesis

Regulation
1. Sterol dependent regulation of gene expression
a. HMG-COA is controlled by SREBP
b. When sterol low, SREBP is cleaved in GOlgi to release transcription factor
c. This transcription factor binds to SRE and activates the synthesis of HMG-CoA
reductase
2. Sterol accelerated enzyme degradation
a. When sterol present, it need to degrade the HMG-CoA to avoid accumulation of
cholesterol
b. HMG-CoA is ubiquitinated and extracted from the membrane where it is then
degraded by proteosome
3. Hormonal regulation
a. Insulin
i. Activates the protein pohsphatase
ii. HMG-CoA dephosphorylate and activate HMG-CoA
b. Glucagon
i. Activates protein kinase
ii. HMG-CoA phosphorylate cause HMG-CoA inactive
4. Inhibition by drug
a. Statin dur are structural analogs of HMG-CoA
b. They are competitive inhibitors of HMG CoA reductase enzyme
5. Sterol-independent phosphorylation and dephosphorylation
a. HMG-CoA is activate when dephosphorylate and inactive when phosphorylate
b. Adenosine monophosphate activate protein kinase and a phosphoprotein
phosphatase control the activity of HMG CoA reductase
c. Decrease ATP will increase AMP that activate kinase cause HMG-CoA inactive
d. It decrease cholesterol synthesis

Excretion
1. Conversion into bile acid and bile salts-excreted in the feces
a. It secrete cholesterol in bile
b. It also transport to intestine for elimination
2. In the intestine, som cholesterol is converted by bacteria into coprostanol and cholestanol
 before excretion
3. Reverse cholesterol transport
a. When there is too much cholesterol in the peripheral tissues, such as the arterial
walls, the ABCA1 receptor is activated. This receptor binds to HDL and transfers
cholesterol to it.
b. HDL then interacts with this receptor and collects cholesterol returning it to the liver.
c. Once in the liver, cholesterol can be either excreted into the bile or converted into
bile acids for excretion.