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Cards (10)

  • Lipoproteins
    • Composed of lipids and proteins (apolipoproteins)
    • Main purpose is to transport energy - the core of lipoprotein essentially represents the cargo transported by lipoproteins
    • Size correlates with its lipids content - higher lipid content means larger size
    • Larger lipoproteins have larger core regions - TAG and CE
    • The larger the lipoprotein, the higher the lipid content than proteins, the lighter it is
  • Apolipoproteins
    • Protein portion of lipoproteins
    • Found on the surface of the lipoproteins
    • Help maintain the integrity of the lipoprotein, keeping it intact
    • Some bind to host cell receptors
    • Some are activators or inhibitors
    • Associates with the lipids because of their amphipathic helix (protein sequences that fold once in contact with a polar/non-polar interface)
  • Lipid absorption
    1. FA rapidly diffuses in the intestine
    2. TAG are acted upon by pancreatic lipase which cleaves them into one or two fatty acids and monoglycerides/diglycerides
    3. Cholesterol is absorbed by the action of the bile
    4. Absorption is via the NPC1-L1 receptor
    5. Cholesteryl ester acted upon by cholesteryl esterase producing cholesterol and fatty acids
    6. Phospholipid is acted upon by the phospholipase enzyme releasing FA and lysophospholipids (also easily absorbed)
    7. The short chain FA from the digestion of TAG, phospholipids, and cholesteryl esters are readily absorbed and are THEN transported by albumin in the blood
  • Chylomicrons
    • Transport DIET-DERIVED lipids
    • Contain large amount of TAG = large but light
    • Large size enables it to reflect light and account for the turbidity of the postprandial plasma
    • Lightweight causes it to float to the top of the stored plasma and form a creamy layer
    • Good source of energy (FA in TAG)
  • Exogenous pathway
    1. The newly synthesized chylomicrons in the intestine are initially secreted into the lymphatic ducts and eventually enter the circulation by the way of the thoracic duct
    2. In the tissues, chylomicrons bind to heparan sulfate and other proteoglycans present in the capillaries of different tissues
    3. The binding to proteoglycan promotes interaction with lipoprotein lipase
    4. Lipoprotein lipase hydrolyzes TAG on the chylomicrons generating fatty acids and glycerol
    5. The fatty acids and glycerol are then taken up by the cells/tissues and are used as a source of energy
    6. Excess fatty acids are then stored in adipose tissues and are stored there as triglycerides. The creation of TAG insides the adipose tissues using glycerol derived from glucose and not from the original na TAG
    7. Once na transfer and TAG to different sites like the muscles and adipose tissues, it becomes a chylomicron remnant, which is then removed by the liver
    8. After lipolysis, chylomicron is converted into chylomicron remnant
    9. Chylomicron remnants are then rapidly taken by the hepatocytes of the liver and are broken down by the lysosomes into free cholesterol, FA and amino acids
  • Very low density lipoprotein (VLDL)
    • Transports hepatic-derived lipids
    • Transfers TAG from the liver to the peripheral tissues
    • Contains large amount of TAG but not as much as chylomicrons
    • Good source of energy (FA in triglycerides)
    • Like chylomicrons, it can also reflect light and account for the turbidity in fasting hyperlipidemic plasma
    • But will not form the cream layer like that of chylomicrons
    • Excess dietary intake carbohydrates, saturated fatty acids and trans fatty acids enhance the hepatic synthesis of TAG, thus many LDL → more CV na sakit
  • Endogenous pathway
    1. VLDL, once secreted into the blood, undergo a lipolytic process similar to that of chylomicrons
    2. VLDL loses core lipids in the action of Lipoprotein lipase and becomes the VLDL remnants (or intermediate density lipoprotein - IDL)
    3. ½ are taken up by the liver and are metabolized just like the chylomicrons, but
    4. ½ of VLDL remnants collect cholesterol and eventually becomes the IDL and LDL
  • Low density lipoprotein (LDL)

    • Transports cholesterol to the different cells in the body
    • Taken up by the cells by binding to LDL receptors present in cells
    • Too much LDL will deposit in the blood vessels
  • LDL uptake and metabolism
    1. Once bound to the receptors, the LDL are endocytosed
    2. Transported to the lysosomes for degradation
    3. TAG component is acted upon by acid lipase to produce glycerol and fatty acids - source of energy
    4. Cholesterol - may be used for membrane synthesis, synthesis of steroid hormones and stored as cholesteryl esters by the enzyme acyl-CoA or cholesterol acyltransferase (ACAT)
  • Reverse cholesterol pathway
    1. High density lipoproteins (HDL) - "good cholesterol"
    2. Responsible for disposing cholesterol
    3. Makes cholesterol to cholesteryl ester
    4. Smallest but the most dense lipoprotein
    5. Has Apo-A1 (activator of Lecithin Cholesterol Acyltransferase ot LCAT)
    6. Cholesterol from non-hepatic tissues is transferred to the liver for metabolism and excretion into the bile
    7. Lipid-poor discoid HDL particles, produced in the liver or the intestine, initiate the efflux of cholesterol and phospholipids from cell membranes via interaction with adenosine triphosphate-binding cassette transporter A1 (ABCA1)
    8. Subsequent action of Lecithin cholesterol acyl transferase or LCAT - the enzyme that helps esterifies excess cholesterol in pre beta-HDL particles and convert them to mature alpha HDL particles
    9. Mature HDL can deliver cholesterol to the liver either directly via scavenger receptor type B1 (SR-B1) or indirectly by exchange of cholesteryl esters to apoB-containing particle for TAG
    10. Cholesteryl esters can be exchanged for TAG in apoB-rich particles (LDL and VLDL) by cholesteryl ester transfer protein
    11. The uptake of apoB-rich particles via hepatic LDL receptors enable the delivery of cholesterol to the liver (around 50% of RCT)