4- Lipid Transport Flashcards
Outline the different groups of lipids and give some here also properties of lipids.
-what is the typical total plasma lipid conc?
- TAGs, FAs, Phospholipids, cholesterol, Vitamins ADEK
- structurally diverse, hydrophobic and lipophilic, insoluble in water, transported in blood bound to carriers, mainly FAs bound to albumin, rest mostly carried on lipoprotein particles
- total lipids= 4000 to 8500 mg/L
- outline the structure and properties of phospholipids and cholesterol.
- what is the general structure of lipoproteins and name the 2 different types of apolipoprotiens found on its bilayer.
- name the 5 distinct classes of lipoproteins according to their density, which is good fat vs bad fat?
- phospholipids= have a polar head (of choline, phosphate and glycerol) which is hydrophilic and non polar tails (of fatty acids) that are hydrophobic w a kink in the leg. Arranged in bilayer w heads out, micelle (ball) w heads out, or liposome (bilayer in the shape of a ball) heads out.
- cholesterol= most synthesised in liver, some from diet, membrane fluidity, precursor of steroid hormones (cortisol, testosterone, oestrogen), precursor of bile acids, transported as cholesterol ester (from cholesterol its esterified w FA to form cholesterol ester).
- lipoproteins are a ball w a phospholipid monolayer w small amounts of cholesterol in bilayer, inside (the cargo) contains TAGs, cholesterol ester & Vitamins ADEK)
- 2 main types= peripheral apolipoprotiens (outer bilayer), integral apolipoproteins (inserted through)
- 5 classes= chylomicrons (least dense, transports dietary fat ie TAGs), VLDL (very low density lipoproteins), IDL (intermediate density lipoproteins), LDL (low density lipoproteins, BAD FAT), HDL (high density lipoproteins, GOOD FAT)
- how are lipoproteins separated according to their densities?
- define apolipoprotiens, give the major classes and their functions
- what are 2 important apolipoprotiens & their function?
- outline the process of chylomicron metabolism.
- density is obtained by flotation ultracentrifugation, the particle diameter is inversely proportional to the density ie LARGE diameter= LOWER density therefore chylomicron are the largest, HDLs are the smallest.
- they are associated proteins on or in the bilayer, 6 major classes= ABCDE&H
- 2 important apolipoprotiens are: apoB (VLDL,IDL,LDL) and apoAI (HDL)
- package water insoluble lipids, cofactors fir enzymes, ligand for CS receptor.
- chylomicrons are loaded into the SI and apoB-48 is added before it reaches the lymphatic system. Travels to the thoracic duct& empties into left subclavian vein and acquires 2 new apolipoprotiens once in blood (apoC and apoE). apoC binds to lipoprotein lipase (LPL- hydrolysis TAGs in chylomicrons, needs apoC as cofactor, found on capillary walls of muscle and adipose) on adipocytes and muscle. Released FAs enter cells depleting chylomicron of its fat content. When TAG reduced to ~20%, apoC dissociates and chylomicron -> chylomicron remnants, they return to liver, LDL receptor on hepatocytes bind to apoE & chylomicron remnants taken up by receptor mediated endocytosis, lysosomes release remaining contents for metabolism.
- outline VLDL metabolism
- outline IDL and LDL metabolism, what is the function of this metabolism
-VLDL= made in liver for transporting TAG to other tissues, apoB100 added during formation and apoC + apoE are added from HDL particles in blood. VLDL binds to LPL on endothelial cells in muscle and adipose and starts to become depleted of TAGs, in muscle= released FAs are taken up for energy, in adipose= released FAs are used for resynthesis of TAGs & stored as fat.
-VLDL-> IDL-> LDL
-as TAG content of VLDL drops, VLDL particles dissociate from the LPL enzyme complex and returns to liver. If VLDL content depletes to ~30%, it will become a short lived IDL particle.
-IDL particles are also taken up by liver or rebind to LPL enzyme to further deplete the TAG content, if depletion up to ~10%, IDL loses apoC and apoE and becomes an LDL
particle (high cholesterol content, low TAG)
-function of this metabolism= LDL is produced which provides cholesterol from liver to the peripheral tissues, these peripheral tissues express LDL receptors and can take up the LDL via receptor mediated endocytosis LDL lack apoC and apoE so are not cleared by liver
-as a result, LDL half life in the blood is much longer making it more susceptible to oxidative damage than HDLP or IDL, oxidised LDLs form foam cells and contribute to forming atherosclerotic plaques.
- previous card mentioned LDLs enter peripheral cells via receptor mediated endocytosis. Outline it.
- outline HDL metabolism
- cells in the peripheral that need cholesterol express LDL receptors on their pm, apoB-100 on LDL acts as a ligand for these receptors, the receptor-LDL complex is taken into the cell via endocytosis into endosomes, they fuse w lysosomes for digestion to release cholesterol and FAs, LDL-R expression is controlled by the cholesterol conc in cell (more if conc low)
- synthesis= nascent HDL synthesised in liver and intestine (low TAG levels), HDL particles can also bud off from chylomicrons and VLDL as they’re digested by LDL, free apoA-I can also get cholesterol and phospholipids from other lipoproteins and cell membranes to form nascent-like HDL
- mature= nascent HDLs accumulate phospholipids and cholesterol from cells lining blood vessels, the hollow HDL fills and particle takes a more globular shape, transfer of lipids into the HDL doesn’t need enzymes.
- reverse cholesterol transport= HDLs can remove cholesterol from cholesterol full cells and return it to the liver, it’s important in BVs as it reduces likelihood of atherosclerosis, ABCA1 proteins in cell facilitates this transfer of cholesterol to HDLs, cholesterol is then converted to cholesterol esters by LCAT.
- fate of mature HDL= taken up by liver via receptors, cells needing extra cholesterol (eg steroid hormone synthesis) use scavenger receptors to get the cholesterol from HDLs, HDLs can also exchange cholesterol ester for TAG with VLDL via action of cholesterol exchange transfer protein (CETP)
Outline each of the lipoproteins transport function.
- Chylomicrons = transport dietary TAGs from intestine to tissues eg adipose
- VLDL= transport TAGs synthesised in liver to adipose for storage
- IDL = short lived precursor of LDL, transports cholesterol synthesised in liver to tissues
- LDL = transports cholesterol synthesised in liver to tissues
- HDL = transports excess cholesterol from cells to liver for disposal as bile salts and to cells needing extra cholesterol
- what are hyperlipoproteinaemias?
- what are they caused by & what are the main classes
- clinical signs?
-raised plasma level of one or more lipoprotein classes
-caused by over production or under removal, defects in enzymes, receptors, apoproteins
-type 1= excess chylomicrons, defective LPL
type 2=defective LDL receptor & associated w CHD, type 2b= associated w CHD, defect unknown, type 3= raised IDL and chylomicron remnants, CHD, defected apoE,
-signs= high cholesterol conc in blood, cholesterol deposits on body; xanthelasma (yellow patches on eyelids), tendon xanthoma (nodules on tendon), corneal arcus (white circle around eye, common in older)
- why is raised serum LDL associated w atherosclerosis?
- how are hyperlipoproteinaemias treated? Give the mechanism of action
- what is the cholesterol tests normal values?
- circulating LDL has higher half life, higher chance of oxidative stress, if oxidised the LDL is recognised and engulfed by macrophages, the lipid laden macrophage is called a foam cell and these accumulate in the intima of BVs walls, forms fatty streak, evolve to atherosclerotic plaque, grows and encroaches on lumen = angina or ruptures causing thrombosis (clot)= MI or stroke
- treatment= first try diet ie reduce cholesterol and saturated lipid intake, stop smoking and exercise more, second try statins (eg atorvastatins) which reduces cholesterol synthesis by inhibiting HMG-CoA reductase or bile salt sequestrants which bind bile salts in GI, forced liver to make more bile salts thus using up cholesterol
- total cholesterol= 5 mmol/L or less, non HDL (ie total- HDL) =4mmol/L or less, HDL= over 1mmol/L men over 1.2mmol/L women, LDL= 3 mmol/L or less
