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Lipoproteins
Uni of Notts, Signalling & Metabolic regulation, year 2, topic 13
| Term | Definition |
|---|---|
| How lipids are transported | Conversion to lipoproteins for solubility. FFAs are bound to albumin |
| General lipoprotein structure | Hydrophobic core of TAGSs & cholesteryl saturated ester surrounded by phospholipid monolayer, free cholesterol, & apolipoproteins |
| How lipoproteins are separated experimentally | Ultracentrifugation separates them by density (lipoproteins with higher protein:lipid ratio are denser & smaller) using solutions like potassium bromide |
| Chylomicrons | Remove dietary TAGs & cholesterol from blood plasma after absorption through small intestine to transport to peripheral tissues. Very low density, 90% TAG. Contains Apo B-48, apo C, & apo E |
| Chylomicron remnants | Cholesterol rich particles remaining after chylomicron hydrolysation by capillary bound lipoprotein lipase for uptake by the liver. Contains apo B-48 |
| VLDLs | Distributes biosynthesised TAGs from liver to peripheral tissues. Contains apo B-100, apo C, & apo E |
| IDLs | VLDL remnants from hydrolysis by LPL which removed TAGs. Half taken up by the liver for processing & half converted to LDL by hepatic lipase to remove TAGs. Contains apo B-100 & apo E |
| LDLs | Main cholesterol transporter in the blood, has an apo B-100 & E shell which is recognised by peripheral tissue LDL receptors to deliver cholesterol & regulate biosynthesis. Contains apo B-100 & apo E (higher LDL receptor affinity) |
| HDLs | Reverses cholesterol transport from peripheral cells that died or underwent membrane cycling back to the liver. Contains acyltransferases to esterify cholesterol. Contains apo A |
| What apo As do | Activates LCAT to esterify cholesterol in HDL |
| What apo CII does | C terminal activates lipoprotein lipase, transcription regulated by FXR/RXR |
| What apo E does | Mediates uptake by liver |
| How apolipoprotein isoforms are generated | Smaller forms are formed from shorter transcripts of full length genes whose mRNA is edited to include a premature stop-codon by tissue specific enzymes |
| Dietary TAG absorption in the intestine | Hydrolysed into MAGs & FFAs before being absorbed into the mucosa & reesrerified |
| Why chylomicrons enter circulation first | Too large to enter capillaries so are excreted through enterocytes into the lymphatic system & lymph vessels called lacteals which transport them through thoracic duct to the heart to enter circulation |
| How chylomicron remnants are taken up by the liver | Apo E binds hepatic remnant receptors & heparin sulphate proteoglycans to initiate endocytosis |
| How VLDLs are formed | Apo B-100 lipidated in ER by micro soma l triglyceride-transfer protein (MTP) |
| Fate of LDL in the liver | Endosome vesicle containing LDL is fused with lysosome to degrade it to cholesterol |
| Scavenger receptor family | Binds charged or oxidised (class A) or normal (class B) LDL & stimulates macrophages to take up oxidised LDL → foam cell formation (lipid laden macrophages) → atherosclerosis plaque formation |
| Why Scavenger receptors are dangerous | Unlike LDL receptors, they are not strongly downregulated by intracellular cholesterol |
| ABCA1 & Tangier disease | Exports cholesterol/phospholipids to Apo A-I to form nascent HDL. ABCA1 mutations → Tangier disease: extremely low HDL & cholesterol accumulation in tissues |
| CETP | Cholesteryl Ester Transfer Protein. Exchanges HDL cholesteryl esters for TAGs from VLDL/LDL |
| SR-BI | Scavenger Receptor B1. Selectively transfers HDL cholesteryl esters into liver/steroidogenic tissues without HDL uptake |
| Why increasing HDL concentration may not be as atheroprotective as scientists think | HDL function matters more than HDL concentration because HDL also carries inflammatory & signalling molecules like Sphingosine-1-phosphate |
| Pre-β HDL (nascent HDL) | Discoidal, lipid-poor HDL made mainly of Apo A-I (+ some phospholipid). It accepts cholesterol/phospholipids from peripheral cells via ABCA1 |
| HDL3 formation & function | LCAT binds Apo A-I on nacent HDL& esterifies free cholesterol → cholesterol moves into HDL core, forming spherical HDL3 for reverse cholesterol transport |
| HDL2 formation & function | HDL3 exchanges cholesteryl esters for TAGs with VLDL via CETP, forming larger HDL2, which delivers cholesterol to the liver via SR-BI |
Created by:
Denny12
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