Cholesterol Flashcards
Where does cholesterol synthesis occur?
Cytoplasm
RLS of cholesterol synthesis
HMG-CoA –> mevalonate
HMG-CoA reductase
MOA of statins
Competitive inhibitor of HMG CoA reductase
Effect of insulin and glucagon on cholesterol synthesis
Insulin dephosphorylates –> activates
Glucagon phosphorylates –> inactivates
Primary bile acids
Cholic acid
Chenodeoxycholic acid
Conjugated primary bile acids become?
Conjugation with TAURINE or GLYCINE
Bile acids –> bile salts
Secondary bile acids
Deoxycholic acid
Lithocolic acid
Where are bile acids and bile salts absorbed
Terminal ileum 95%
MOA of cholestyramine
Bile acid sequestrant
Bind bile acids in the gut, preventing their reabsorption, promoting excretion
Lipoprotein with lowest density and largest size
ChyLOmicron
Think: malaking LOBO
- largest size = most lipid
- lowest density = magaan = least protein
Densest lipoprotein
HDL
Apolipoprotein necessary for activation of lipoprotein lipase
Apo C-II
II = LL = lipoprotein lipase
Function of lipoprotein lipase
Degrades TAGs within the chylomicron
Degradation of TAGs form what products
Fatty acids –> stored by adipose or used by muscle
Glycerol –> used by liver
Stimulus for lipoprotein lipase synthesis
Insulin - fed state
Where is VLDL produced
Liver
Function of VLDL
Carry triglycerol from the liver to the peripheral tissues
In the periphery, it will be degraded by lipoprotein lipase also
Who donates Apo C-II and Apo-E?
HDL
As the VLDL exists the liver as nascent VLDL, what apoprotein does it carry?
Apo B-100
Primary function of LDL
Provide cholesterol to peripheral tissues or to return it to the liver
What receptors do peripheral tissue recognize?
Apo B-100
To whom does HDL give Apo C-II and Apo E
Chylomicrons
VLDL
Function of Apo E
Required for receptor mediated endocytosis of IDLs and chylomicron remnants to the liver
Cholesterol immediately esterified by — when it is taken up by HDL
PCAT or LCAT
phosphatidylcholine: cholesterol acyltransferase
Or lecithin
Responsible for reverse cholesterol transport
HDL
Cholesterol from peripheral cells –> to HDLs –> to liver for bile acid synthesis or disposal via bile
Activates nascent HDL
Apo A-I
Abetalipoproteinemia - deficiency?
Apo B-48 (chylomicrons) and Apo B-100 (VLDL, LDL)
Intestinal malabsorption with accumulation of lipids in intestines and liver
Familial lipoprotein lipase - deficiency?
Lacks lipoprotein lipase - unable to degrade
High VLDL and chylomicron levels in plasma
Xanthomas and pancreatitis
No increased risk for CAD
Familial Hypercholesterolemia - deficiency?
LDL receptors
High LDL levels in blood
These receptors are important for uptake by liver in tissues
Xanthomas and xanthelasmas
Increased risk for CAD
Activates LCAT to produce cholesterol esters
Apo A-1
Where are chylomicrons assembled
Intestinal mucosal cells (from dietary lipids - primarily triglycerol)
Primary component of nascent VLDL
Triacylglycerol
When peripheral tissues endocytose LDLs, what happens?
Contents are degraded in the lysosomes
Where are HDLs synthesized
Liver and intestines
Responsible for esterifying cholesterol from other lipoproteins
HDL
Using PCAT/ LCAT
After esterifiation of cholesterol via PCAT/ LACT, what happens
It is activated by Apo A-1 and delivered to the liver (aka reverse cholesterol transport)
Deliver cholesterol to liver for elimination
HDL
Deliver cholesterol to peripheral tissues
LDL
Deliver de novo TAG to peripheral tissues
VLDL
Deliver dietary TAG to peripheral tissues
Chylomicrons
Lowest TAG content
HDL
Highest TAG content
Chylomicrons
Highest cholesterol content
LDL
Lowest cholesterol content
Chylomicrons
Role of exogenous chenodeoxycholic acid
Increases cholesterol solubility in bile, acting like an emulsifying agent
Once glycerol (product of lipoprotein lipase degradation) is produced, what will happen?
It is converted to DHAP and enters glycolysis or gluconeogenesis
What activates pancreatic lipase
Trypsin
Found in intestinal lumen
What activates hormone sensitive lipase?
Glucagon
During fasting
Found in the liver
Highest protein content
HDL
‘Heavy’
