Lipoproteins Flashcards
Lipoprotein
Physical complex of lipid and protein
Apo A
Activates LCAT (on HDL)
Apo B
Involved in receptor-lipoprotein interaction
B48 - Digestion in chol for CM
B100 - Liver, endogenous FAT
ApoE
Involved in receptor lipoprotein interaction
ApoC
Activates lipoprotein lipase (LPL)
Type 1 Hyperlipidemia (ApoC or LPL def)
HDL donates ApoE and ApoC to CM in blood
Bloods modes of lipid transport
Albumin, FA from adipose
CM, dietary lipids (intestines) to other tissue
Endogenous lipid from liver to tissue (lipoproteins)
Transport of Chol from tissue to liver (HDL - ApoA 1,2,4 activating LCAT
Chylomicrons
Delivery dietary lipids from intestine to tissue
Prominently TG, Apo B/C/E
ApoB48, chol esters, lymph travel
VLDL
deliver endogenous lipids from liver to tissue
mostly triglycerides, ApoB/C/E
ApoB100
Chol, blood travel
IDL
precursor for LDL, return lipids to Liver
VLDL given up ApoC (LPL) - ApoB100, ApoE. Liver receptor: ApoB100/E (endosome - lysosome IDL breakdown). Cholesterol donated to HDL for LCAT activity
LDL
deliver chol to tissue. Only ApoB100, single copy. Chol esters (FA). ApoB100 docks with LDL receptor, clathrin coated pits for endocytosis. Low pH allows dissociation of LDL-R from LDL (recycled LDL-R lose affinity each time so need new expression)
Lysosomal esterase converts chol ester to chol
HDL
Deliver chol from tissue to liver
HDL LCAT
on surface in blood: esterify chol for IDL to LDL to trap chol ester within lipoprotein. ApoA involved in esterfication of cholesterol, given back to IDL, activates LCAT (Lecithin-cholesterol acyl transferase)
HDL creation
Created in liver. Free ApoA 1 ciruclates and acquires cholesterol and PL’s becoming HDL. Attracts unesterfied chol from lipoproteins (ApoA1 and ApoE are main lipoproteins)
HDL CETP
Cholesterol ester transfer protein, transfers cholesterol esters from HDL to VLDL and HDL accepts TAGs.
HDL2 - gain more cholesterol and becomes arthogenic protective, chol back to liver
HDL and Hepatic Lipase
Removes TAG from HDL in space of Disse, hydrolyzes HDL to HDL2-3 (athroprotective). This is not activated by ApoC2 or attach TAG in CM and VLDL
Cell metabolism of Chol
Norm levels = 200 mg/dl
De novo synth = Acetyl Coa (from glucose)
Biosynth = HMG-CoA Reductase
Simvastatin = HMG-CoA Reductase inhib
Cholestyramine - prevents bile acid absorb (excreted through feces, increased expression of LDL-R)
ACAT
Acyl-CoA chol acyl transferase, synthesizes chol ester for storage. Intestinal mucosa involved in remaking chol ester.
Packaged in CM
TG, Chol, PL’s
Abetalipoproteinemia
No apoB4 = MTP deficient (MTP transfers TG, chol to ApoB48)
High LDL chol
High levels of LDL chol reduce LDL gene expression and since LDL-R are degraded after recycle this reduces total number of LDL-R therefore preventing excess IC chol build up
LDL-R
Binds LPL with ApoB100. Can’t bind oxLDL
FH
Familial hypercholesteremia is a mut in LDL-R leading to atherosclerosis
OxLDL
Reactive oxygen species bind with ApoB100 therefore damaging it and it becomes foreign. This binds with macrophages via Scavenger receptor (SR-A) (SR not downreg by chol). MAcropahges become bloated and enter subendo becoming a foam cell (useless) and begins athersclerotic plaque.
HDL and ApoA
HDL has ApoA on its surface, can bind cholesterol and activate LCAT, chol ester, transfer to IDL, then LDL. More HDL = more ability to scavenger cholesterol (reverse chol transport as hepatocyte expresses SR-B receptor which docks with HDL and deposits chol back to liver)
