TBPP_The ins and outs of HDL

mostly spherical, fatty core: cholesteryl esters, little triglycerides, surrounded by: phopholipids, unesterfied cholesterol, apolipoproteins, minor population of discoidal particles

apoA-1: 70% of HDL protein, import to cholesterol efflux, activates LCAT, anti-oxidant and anti-inflammatory, mostly in spherical HDL. / apoA-2: 20% of HDL, function unknown, increases stability, mostly in spherical HDL / apoA-4: minor, similar function to apoA-1, 1/2 spherical HDL, 1/2 in lipid-free form / apoA-V: minor, metabolism of triglyceride rich lipoproteins / apoE: minor, involved in cholesterol efflux, for recognition of HDL by cell receptors, mostly HDL. / apoC-1/2/3: minor, metabolism of triglyceride rich lipoproteins / apoD, apoJ, apoL, apoM: minor, functions unknown

main layer, aphipatic helices: one side charged (affinity for aqueous phase), other side hydrophobic (binding to lipid), 2 regions joined by hinge (plastic, several formations possible), 1 g/L

HDL smallest and densest lipoproteins of plasma, heterogeneous with many subpopulations (different shapes, sizes, densities, composition, surface charges), 2 major subpopulations: apoA1 but no apoA2, both apoA1 and apoA2

all starts in liver and intestine by secretion of a lipid poor protein (apoA-1), through ABCA1 receptors, phospholipids and cholesterol quickly acquired: pre-Beta discoidal HDLs. Cholesterol in discoidal HDL is esterfied by LCAT. The cholesterin-esters arent water soluble and move inside of the particle to form a lipid core. change of pre-beta to alpha spherical particles. larger spherical can also be remodelled to smaller sizes by cholesterol-esters and triglyceride depletion. Some apo-A1 lost during the process and can pick up new phospholipids and cholesterol from cell membranes (discoidal HDLs)

ATP-binding cassette A1/G1 (ABCA1/G1): moves cholesterol to poor apoA-1/spherical HDLs, scavenger receptor type B (SR-B1): in liver, selectively takes cholesterol from HDLs, Lecithin (Cholesterol Acyltransferase LCAT): catalyses esterification of cholesterol in HDL (80% esterfied), Cholesteryl ester transfer protein (CETP): redistributes cholesterolesters and triglycerides between HDLs and triglyceride-rich lipoproteins. phospholipid transfer protein (PTLP): transfer phosholipids between HDLs and other lipoproteins, Hepatic Lipase (HL): resides on surface of liver cells, substrate: HDL triglyceride. Lipoprotein Lipase (LPL): on cell surface, hydrolyses triglycerides. Endothelial Lipase (EL): on cell surface, substrate: HDL phospholipid.

plasma cholesterol transport and unrelated to cholesterol transport

movement of cholesterol from extrahepatic tissues back to the liver, 4 distinct processes. ABCA1: efflux of cholesterol from cells to lipid poor apoA-1. ABCG1: efflux of cholesterol from cells to large spherical HDLs. SR-B1: bidirectional transfer of cholesterol between cells and spherical HDLs, only if LCAT-mediated concentration gradient. passive diffusion: of cholesterol to spherical HDLs, if LCAT-mediated concentration gradient.