Mapa mental

Serum lipids

Valentina Ardila Mora Medicina Inglês

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Serum lipids

Plasma lipid composition
- triacylglycerols (16%)
- phospholipids (30%)
- cholesterol (14%)
- cholesteryl esters (36%)
- unesterified long-chain fatty acids (or FFAs) (4%)
  - metabolically the most active plasma lipid
    - from peripheral adipocytes to other tissues.
Lipoproteins
- complexes of lipid & protein molecules
  - Major groups
    - chylomicrons
      - derived from intestinal absorption of
        dietary triacylglycerol
        other lipids
      - main apoprotein
        apo B (B-48)
        48% of apo B-100
        from B-100 synthesized in the liver
        synthesized in the intestine
    - VLDL very-low-density lipoprotein
      - derived from the liver
        endogenous triacylglycerol exportation
        pre-β-lipoprotein
        cholesterol
      - main apoprotein
        apo B
    - LDL low-density lipoprotein
      - final stage of VLDL catabolism
      - cholesterol
      - main apoprotein
        apo B-100
      - β-lipoprotein
    - HDL high-density lipoproteins
      - cholesterol and phospholipids transport
      - metabolism of
        VLDL
        chylomicron
      - Source
        Liver
        intestine
        VLDL
        chylomicrons
      - main apoprotein
        apo As
      - α-lipoprotein
    - IDL intermediate-density lipoprotein
      - Triacylglycerol
      - cholesterol
      - main apolipoprotein
        apo B
  - Composition
    - nonpolar lipid core
      - triacylglycerol
      - cholesteryl ester
    - single surface layer
      - amphipathic phospholipids
      - cholesterol
    - protein moiety
      - Apoproteins
        Roles
        form lipoprotein structure
        enzyme cofactors
        C-II
        lipoprotein lipase
        A-I
        lecithin:cholesterol acyltransferase LCAT
        enzyme inhibitors
        apo A-II
        lipoprotein lipase
        apo C-III
        lipoprotein lipase
        apo C-I
        cholesteryl ester transfer protein
        act as ligands
        for lipoprotein receptors in tissues
        apo B-100
        LDL receptor
        apo E
        LDL receptor
        LDL-receptor–related protein-1 (LRP-1)
        recognizes remnant lipoproteins
        apo A-I
        HDL receptor
        apo A-IV
        chylomicron metabolism
        regulator
        satiety
        glucose homeostasis
        therapeutic target for treatment
        diabetes
        obesity
        apo D
        factor in neurodegenerative disorders.
        location
        integral
        cannot be removed
        apo B
        peripheral
        can transfer to other lipoproteins
        apo C
        C-I
        C-II
        C-III
        apo E
        VLDL
        HDL
        chylomicrons & remnants
  - Function
    - transportation and delivery
      - fatty acids
      - triacylglycerol
      - cholesterol
  - Hepatocytes and intestinal epithelial cells
    - use cholesterol for their secretion
Metabolism of Triglyceride Rich Lipoproteins in Plasma
- Hydrolysis by lipoprotein lipase
  - Lipoprotein lipase enzyme in capillaries endothelium
    - Location
      - heart
        low Km
        Result
        fatty acids from adipose tissue
        head to the heart in the starved state
        when plasma triacylglycerol decreases
      - adipose tissue
        high Km
        Result
        VLDL receptor
        VLDL binding
        fatty acids from VLDL triacylglycerol to adipocytes
        insulin enhances
        lipoprotein lipase synthesis
        translocation to capillary endothelium
      - spleen
      - lung
      - renal medulla
      - aorta
      - diaphragm
      - lactating mammary gland
        fatty acid uptake
        milk fat synthesis
      - skeletal muscle
    - cofactors
      - phospholipids
      - apo CII
      - heparin
    - inhibitors
      - apo AII
      - apo CIII
        increases VLDL production
    - hydrolysis of lipoproteins attached to the enzyme
      - Triacylglycerol from chylomicrons & VLDL
        diacylglycerol
        monoacylglycerol
        FFA
        some return to the circulation
        attached to albumin
        majority transported into the tissue
        glycerol
      - Formation of lipoprotein remnants
        Loss of
        70-90% of triacylglycerides
        chylomicron remnant
        half the diameter of the parent chylomicron
        enriched in cholesterol and cholesteryl esters
        taken up by the liver by endocytosis
        cholesteryl esters and triacylglycerols are hydrolyzed and metabolized
        free cholesterol
        supressses cholesterol biosynthesis (downregulates HMGCoA)
        LDL receptor supression & degradation
        Uptake mediated by
        apo E dependent receptors
        LDL (apo B100, E) receptor
        LDL receptor–related protein1 (LRP1)
        require
        Apo E3
        Apo E4
        B48 is degraded
        VLDL remnants
        intermediate-density lipoprotein (IDL)
        taken up by the liver
        LDL (apo B100, E) receptor
        mostly metabolized to LDL in the circulation
        involves removal of residual triglycerides by hepatic lipase
        beta shift (high LDL)
        plasma LDL accumulation
        Content
        one apo B100 is conserved
        cholesteryl esters
        hypertriglyceridemic states
        low conversion to LDL
        apo C
        returns to HDL
    - GPIHPB1 organizes the complex
    - Lipase maturation factor 1 (LMF1)
      - lipoprotein lipase
      - endothelial lipase
      - hepatic lipase
        acts as a ligand for remnant uptake
        hydrolyzes
        remnant triacylglycerol & phospholipid
- Biologic regulation of lipoprotein lipase
  - insulin
    - LPL is transcriptionally upregulated in adipose tissue
      - fatty acid storage
  - prolonged fasting
    - adipose tissue LPL activity falls
  - diabetic ketoacidosis
    - adipose tissue LPL activity falls
      - prevents fatty acid storage
- Effect of dietary fat restriction
  - normally: 75 -100 g of triglyceride in chylomicrons a day
    - liver exports 10-30g in VLDL.
      - At triglyceride levels 800 -1000 mg/dL
        LPL saturation
        acute restriction of dietary fat is necessary
- lipoprotein half live
  - chylomicrons
    - 5 -20 min
  - VLDL
    - 0.5 -1 h
  - LDL
    - 2½ days
Metabolism of HighDensity Lipoproteins
- Sources of HDL
  - produce HDL apolipoproteins
    - liver
    - intestine
  - chylomicrons and VLDL hydrolysis of triglycerides
    - liberated excess free cholesterol and phospholipids
      - phospholipid transfer protein
        transfers phospholipids to HDL
      - Free cholesterol acquired by HDL
        esterified by LCAT secreted by liver
        1 mol of fatty acid from lecithin
        to the hydroxyl group of unesterified cholesterol
        cholesteryl esters
- Metabolic roles for HDL
  - HDL are carriers of C apolipoproteins
    - transfer apo C to nascent VLDL & chylomicrons
  - deliver cholesterol with LDL
    - adrenal cortex
    - gonads
      - steroidogenesis
  - centripetal cholesterol transport
    - Unesterified cholesterol exported by ABCA1
      - acquired from tissues membranes by prebeta1 HDL
        esterified by LCAT
        passing through other HDL
        before the cholesteryl esters are incorporated into α-HDL
    - Cholesterol effluxed from macrophages by ABCG1
      - acquired by larger HDL
    - cholesteryl esters transferred to
      - LDL & triglyceride rich lipoproteins
        by cholesteryl ester transfer protein (CETP)
      - hepatocytes
        by SRB1 receptors
        excretion via the bile
        reverse cholesterol transport
- HDL catabolism
  - pathways are not yet known
    - Apo AI & Apo A-II removed from plasma
      - degradation in
        liver
        kidney

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Descrição: Medicina Mapa Mental sobre Serum lipids, criado por Valentina Ardila Mora em 11-10-2020.
Criado por: Valentina Ardila Mora
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Serum lipids

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