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LIPIDS, Concept Map - Coggle Diagram

- - - - 4 major functions
        
        Structural Role
        
        Guide the formation of lipoproteins
        
        Ligand for apoprotein receptors
        
        Activators or inhibitors of enzymes related to lipid metabolism
      - Types
        
        Apo A-I
        
        Molecular Weight
        
        28,000
        
        Primary
        Source
        
        Liver,
        Intestine
        
        Lipoprotein
        Association
        
        HDL, chylomicrons
        
        Function
        
        Structural protein for HDL,
        Activates LCAT
        
        Apo A-II
        
        Molecular Weight
        
        17,000
        
        Function
        
        Structural protein for HDL,
        Activates hepatic lipase
        
        Primary
        Source
        
        Liver
        
        Lipoprotein
        Association
        
        HDL, chylomicrons
        
        Apo A-V
        
        Function
        
        Promotes LPL mediated
        TG lipolysis
        
        Primary
        Source
        
        Liver
        
        Molecular Weight
        
        39,000
        
        Lipoprotein
        Association
        
        VLDL,
        chylomicrons, HDL
        
        Apo A-IV
        
        Primary
        Source
        
        Intestine
        
        Molecular Weight
        
        45,000
        
        Function
        
        Unknown
        
        Lipoprotein
        Association
        
        HDL, chylomicrons
        
        Apo B-48
        
        Molecular Weight
        
        241,000
        
        Function
        
        Structural protein for
        chylomicrons
        
        Primary
        Source
        
        Intestine
        
        Lipoprotein
        Association
        
        Chylomicrons
        
        Apo B-100
        
        Primary
        Source
        
        Liver
        
        Lipoprotein
        Association
        
        VLDL, IDL, LDL, Lp
        (a)
        
        Function
        
        Structural protein, Ligand
        for LDL receptor
        
        Molecular Weight
        
        512,000
        
        Apo C-I
        
        Function
        
        Activates LCAT
        
        Lipoprotein
        Association
        
        Chylomicrons,
        VLDL, HDL
        
        Molecular Weight
        
        6,600
        
        Primary
        Source
        
        Liver
        
        Apo C-II
        
        Lipoprotein
        Association
        
        Chylomicrons,
        VLDL, HD
        
        Primary
        Source
        
        Liver
        
        Function
        
        Co-factor for LPL
        
        Molecular Weight
        
        8,800
        
        Apo C-III
        
        Molecular Weight
        
        8,800
        
        Primary
        Source
        
        Liver
        
        Lipoprotein
        Association
        
        Chylomicrons,
        VLDL, HDL
        
        Function
        
        Inhibits LPL and uptake of
        lipoproteins
        
        Apo E
        
        Primary
        Source
        
        Liver
        
        Function
        
        Ligand for LDL receptor
        
        Molecular Weight
        
        34,000
        
        Lipoprotein
        Association
        
        Chylomicron
        remnants, IDL, HDL
        
        Apo (a)
        
        Molecular Weight
        
        250,000-
        800,00
        
        Primary
        Source
        
        Liver
        
        Lipoprotein
        Association
        
        Lp (a)
        
        Function
        
        Inhibits plasminogen
        activation
  - - - Size
        
        25-35nm
      - Density
        
        1.006-
        1.019g/ml
      - Major Lipids
        
        Triglycerides
        Cholesterol
      - Major Apoproteins
        
        Apo B-100, Apo E, Apo C
      - Made by
        
        Removal of triglycerides from VLDL by muscle and adipose tissue
      - Pro-atherogenic
    - - Size
        
        18-25nm
      - Density
        
        1.019-
        1.063g/ml
      - Major Lipids
        
        Cholesterol
      - Major Apoproteins
        
        Apo B-100
      - Derived from
        
        VLDL and IDL particles
      - Function
        
        Carries the majority of the cholesterol that is in the circulation.
      - Pro-atherogenic
      - LDL Metabolism
        
        Levels of plasma LDL are determined by the rate of LDL production and the rate of LDL clearance, both of which are regulated by the number of LDL receptors in the liver.
        
        The levels of LDL receptors in the liver are mainly regulated by the cholesterol content of the hepatocyte.
        
        If cholesterol levels in the cell are high, then the SREBPs remain in the endoplasmic reticulum in an inactive form and do not stimulate LDL receptor synthesis.
        
        Cholesterol in the cell is oxidized and oxidized sterols activate LXR, which stimulates the transcription of E3 ubiquitin ligase that mediates the ubiquitination and degradation of the low density lipoprotein receptor
        
        The LDL receptor is targeted for degradation by PCSK9, a secreted protein that binds to the LDL receptor and enhances LDL receptor degradation in the lysosomes
        
        1 more item...
    - - Density
        
        0.930-
        1.006g/ml
      - Size
        
        30-80nm
      - Major Lipids
        
        Triglycerides
      - Major Apoproteins
        
        Apo B-100, Apo E, Apo C
      - Produced by
        
        Liver
      - Pro-atherogenic
      - Formation
        
        In the liver triglycerides and cholesterol esters are transferred in the endoplasmic reticulum to
        newly synthesized Apo B-100 mediated by MTP.
        
        If the supply of triglyceride is limited the newly synthesized Apo B is rapidly degraded.
        
        MTP is required for the early addition of lipid to Apo B-100 particles but additional lipid is added via pathways that do not require MTP.
        
        Loss of function mutations in either Apo B-100 or MTP result in Familial hypobetalipoproteinemia or abetalipoproteinemia
      - Metabolism of VLDL (Endogenous pathway)
        
        Synthesized in liver
        
        Formation of Nascent VLDL (TGs, Ch, ChE, PLP, Apo B-100)
        
        Formation Mature VLDL(TGs, Ch, ChE, PLP, Apo B-100, C, E)
        
        Formation of Remnant VLDL (IDL) (TGs, Ch, ChE, PLP, Apo- B-100, E)
        Apo C- II activates Lipoprotein lipase
        
        IDL is taken up in the liver by apo E Receptor present in the liver and is transformed to LDL called as Lipoprotein Cascade pathway.
        
        1 more item...
    - - Size
        
        ~30
      - Density
        
        1.055-
        1.085g/ml
      - Major Lipids
        
        Cholesterol
      - Major Apolipoproteins
        
        Apo B-100, Apo (a)
      - Physiologic function is unknown.
      - Pro-atherogenic
      - Composition
        
        an LDL molecule and a unique apolipoprotein (a) which is attached to the
        Apo B-100 of the LDL via a single disulfide bound
      - Elevated plasma Lp(a) levels are associated with an increased risk
        of atherosclerosis
      - The kidney appears to play an important role in Lp
        (a) clearance
    - - Density
        
        0.930-
        1.006g/ml
      - Size
        
        30-80nm
      - Major Lipids
        
        Triglycerides
        Cholesterol
      - Major Apoproteins
        
        Apo B-48, Apo E
      - Formed by
        
        Removal of triglyceride from chylomicrons by peripheral tissues
      - Pro-atherogenic
    - - Density
        
        1.063-
        1.210g/ml
      - Size
        
        5- 12nm
      - Major Lipids
        
        Cholesterol
        Phospholipids
      - Major Apolipoproteins
        
        Apo A-I, Apo A-II, Apo C,
        Apo E
      - Function
        
        Reverse cholesterol transport from peripheral tissues
        to the liver.
      - Anti-atherogenic.
      - Method of Classification
        
        Density gradient ultracentrifugation
        
        Types
        
        HDL2, HDL3, Very high-density HDL
        
        Nuclear magnetic resonance
        
        Types
        
        large, medium, and small
        
        Gradient gel electrophoresis
        
        Types
        
        HDL 2a, 2b, 3a, 3b, 3c
        
        2-dimensional gel electrophoresis
        
        Types
        
        pre-beta 1 and 2, alpha 1, 2, 3, 4
        
        Apolipoprotein composition
        
        Types
        
        A-I particles, A-I: A-II particles, A-I: E particles
      - Formation
        
        HDL is synthesized and secreted both in liver and intestine
        
        Apo C and Apo E are synthesized in liver and transported from liver HDL to intestinal HDL when the latter enters the plasma
        
        HDL major function is to act as repository for apo C and apo E required in VLDL and chylomicron metabolism
        
        Nascent HDL consist of discoid phospholipid bilayer containing apo A and free cholesterol
      - Reverse Cholesterol Transport
        
        Macrophage free cholesterol efflux to apolipoprotein AI via the ATP-binding cassette transporter A1 (ABCA1) yields nascent high-density lipoprotein (nHDL)
        
        nHDL esterification by lecithin:cholesterol acyltransferase (LCAT) gives spherical HDL
        
        Selective hepatic uptake of HDL cholesterol ester. SR-B1: scavenger receptor class B type 1
      - Metabolism
        
        Discoid HDL appears in plasma from gastrointestinal track, liver and from pre-beta HDL.
        
        LCAT forms lacunae in the shell of discoid HDL by forming cholesterol esters which are mabed to the centre of the molecule thus forming HDL2 of low density.
        
        The lacunae gets filled with the cholesterol from extra hepatic tissue.
        
        This forms HDL3 of further low density
        
        HDL 3 is taken by the liver and converted to HDL2 releasing apo A1
        
        1 more item...
    - - Density
        
        <0.930 g/ml
      - Size
        
        75-
        1200nm
      - Major Lipids
        
        triglygerides
      - Major Apoproteins
        
        Apo B-48, Apo C, Apo E, Apo
        A-I, A-II, A-IV
      - Made by
        
        intestine
      - Function
        
        Involved in the
        transport of dietary triglycerides and cholesterol to peripheral tissues and liver.
      - Pro-atherogenic
      - Exogenous Lipoprotein Pathway
        
        Exogenous pathway of lipid metabolism In the intestinal cell, absorbed free fatty acids combine with glycerol to form triglycerides, and, to a lesser degree, absorbed cholesterol is esterified to form cholesteryl esters.
        
        These lipids are assembled as chylomicrons; the main
        apolipoprotein (apo) is B-48, but apo C-II and E are acquired as the chylomicrons enter the circulation.
        
        Apo C-II is a cofactor for lipoprotein lipase which makes the chylomicrons progressively smaller in part by
        hydrolyzing the core triglycerides and releasing free fatty acids.
        
        The chylomicron remnants that are cleared from the circulation by hepatic chylomicron remnant receptors for which apo E is a high-affinity ligand.
      - Chylomicron Metabolism
        
        Formation of Nascent Chylomicron- contains triglyceride, cholestryl ester, cholesterol, lipid, apo B-48 & apo A.
        
        Formation of Mature Chylomicron- by receiving apo C-II and apo E from HDL.
        
        Formation of Remanant Chylomicron– Apo C-II activates Lipoprotein Lipase
        
        Uptake of Remnant Chylomicron
  - - - LDL Binding
        
        Internalization
        
        Lysosomal Hydrolysis
        
        Regulatory actions
    - - LDL Receptor Related Protein (LRP)
        
        Expressed in
        
        Multiple tissues including the
        liver
        
        Function
        
        Recognizes Apo E and mediates the uptake of chylomicron remnants and IDL
      - Class B Scavenger Receptor B1 (SR-B1)
        
        Expressed in
        
        Liver, adrenal glands, ovaries, testes, macrophages, and other cells
        
        Function
        
        Mediates the selective uptake of cholesterol esters
        from HDL particles and facilitates the efflux of cholesterol from
        the cell to HDL particles
  - - - Expressed in
        
        Hepatocytes, enterocytes, and macrophages
      - Function
        
        Mediates the transport of cholesterol and phospholipids from the cell to lipid poor HDL
        particles (pre-beta-HDL)
    - - Expressed in
        
        Many different cell types
      - Function
        
        Mediates the efflux of cholesterol from
        the cell to HDL particles.
    - - Function
        
        Mediate the movement of plant sterols and cholesterol from inside
        the enterocyte into the intestinal lumen
      - Expressed in
        
        liver and intestine
    - - Expressed in
        
        Intestine
      - Function
        
        Mediates the uptake of cholesterol and plant sterols
        from the intestinal lumen into the enterocyte
  - - - Mediates the hydrolysis of
        triglycerides and phospholipids in IDL, HDL and LDL
    - - Hydrolyzes the phospholipids in HDL
    - - Hydrolyzes the triglycerides carried
        in chylomicrons and VLDL to fatty acids
    - - Catalyzes the synthesis of cholesterol esters in HDL
        by facilitating the transfer of a fatty acid from position 2 of lecithin to cholesterol.
    - - Mediates the transfer of cholesterol esters from HDL to VLDL, chylomicrons, and LDL and the transfer of triglycerides from VLDL and chylomicrons to HDL