Dyslipidemias Flashcards
What is the makeup of lipoproteins?
Lipid core
Phospholipid monolayer
Structural apolipoproteins
What are the different apo-lipoproteins?
Apo B-100: VLDLs, IDLs, LDLs bind the LDL receptor
Apo B-48: Chylomicrons structrual role only
Apo A-I: HDL
Activates LCAT
Where are the different Lipoproteins made?
Chylomicrons-Enterocytes VLDLs Liver IDLs In circulation from VLDL LDLs In circulation from IDL HDLs Liver/Intestine 80/20
What is the role of the liver in cholesterol Metabolism?
Site of biosynthesis
Liver HMG-CoA Reductase most effected by statins
Major route for cholesterol elimination
Major distribution point for cholesterol
What are the key enzymes of lipid metabolism?
HMG-CoA Reductase Lipoprotein Lipase Hepatic Lipase CETP(Cholesterol ester transfer protein) LCAT(Lecithin cholesterol acyl transferase)
What is the action of HMG-CoA Reductase?
Reduces HMG-CoA Conversion to mevalonic acid in the RLS of Cholesterol biosynthesis
What is the action of Lipoprotein Lipase?
Hydrolyzes TG core Of Chylomicrons, VLDL, and IDL
- induced by insulin
- located in capillary walls
What is the action of Hepatic Lipase?
Hydrolyzes TAGs in IDL to facilitate conversion to LDL
What is the action of CETP?
Transfers Cholesteryl esters from HDL to other lipoproteins in exchange for TG phospholipids and cholesterol
-Present on HDL
What is the action of LCAT?
Transfers fatty acids from Lecithin to Cholesterol to form Chol. Esters in HDL. Keeps Chol concentration low in the phospholipid monolayer
-Present on HDL
What are the Apo-B containing Lipoproteins?
LDL
IDL
VLDL
Chylomicrons
What is Lipoprotiiene a?
Attached to B-100 and creates a pro-thrombotic state.
Structural similarity to plasminogen
Carried Oxidized phospholipids resulting in an increased inflammatory and atherogenic and thrombotic risk.
What is the function of HDL cholesterol?
Made in the liver
apo A1
Removes free cholesterol from extrahepatic tissue
Esterification of C to CE
Transports TG, C/CE back to the liver for excretion
-direct
-indirect
What are the pathways for HDL Transporting TG, C/CE back to the liver for excretion
- direct
- indirect
Dir: C, TAGs and especially CE directly to the liver via endocytosis
Indirect: Transfer some CE to LDL via CETP which is then taken up by the liver LDL receptor
What is the role of the liver in reverse cholesterol transport?
Conv. Cholesterol to bile acids
Bile acids aid in digestion and are excreted in feces
Some reabsorbed in the ileum
What are some other actions of HDL?
Antioxidant, Antiinflammatiory, Profibrinolytic
What is the purpose of Chylomicrons?
Deliver Dietary TAG FAs to tissues by LPL
What is the purpose of Chylomicron Remnants?
Deliver remaining chylomicron lipids to the liver via endocytosis
What is the purpose of VLDLs?
Deliver TAG FAs from the liver the extra hepatic tissues
What is the purpose of IDLs?
Deliver TAG FAs to Extra hepatic tissues AND BACK TO THE LIVER via HL
What is the purpose of LDLs?
Deliver C and CE to tissues including the liver via ENDOCYTOSIS.
What is the purpose of HDLs?
Reverse cholesterol transport from Extra hepatic tissues to the liver vi endocytosis or indirectly by transferring CE to LDL via CETP
Who will statins work for?
Intermediate to very high cholesterol and even very late life patients
How are lipoproteins measured?
Lipoprotein analysis after 12-14 hrs fasting
TC and HDL can be measured fasting or non fasting