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  <head>
    <title>089-02 Fatty-acid synthesis, membrane lipids, lipoproteins, cholesterol, and lipid signalling</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Lipid synthesis, lipoproteins, and signalling">
      <outline text="Purpose and risks of lipid synthesis">
        <outline text="Excess carbon and reducing power stored"/>
        <outline text="Hydrophobic surfaces kept from water"/>
        <outline text="Dysregulation: steatosis, atherosclerosis, toxicity"/>
      </outline>
      <outline text="Fatty-acid synthesis">
        <outline text="Cytosol of liver and adipose"/>
        <outline text="Acetyl-CoA exported as citrate">
          <outline text="ATP-citrate lyase cleaves in cytosol"/>
          <outline text="Malic enzyme supplies NADPH"/>
        </outline>
        <outline text="Acetyl-CoA carboxylase: committed step">
          <outline text="Citrate activates, acyl-CoA inhibits"/>
          <outline text="Insulin activates, AMP kinase inhibits"/>
          <outline text="Malonyl-CoA also blocks mitochondrial entry"/>
        </outline>
        <outline text="Fatty-acid synthase on acyl-carrier protein">
          <outline text="Condense, reduce, dehydrate, reduce"/>
          <outline text="Palmitate, then elongation and desaturation"/>
        </outline>
      </outline>
      <outline text="Essential fatty acids and glycerolipids">
        <outline text="Linoleic and alpha-linolenic are essential">
          <outline text="Limited conversion to omega-6 and omega-3"/>
          <outline text="Omega-3 label does not mean equal effect"/>
        </outline>
        <outline text="Glycerol-3-phosphate backbone">
          <outline text="Adipose relies on glucose-derived route"/>
        </outline>
        <outline text="Phosphatidic acid branch point"/>
      </outline>
      <outline text="Membrane lipids">
        <outline text="Phospholipids remodelled by deacylation"/>
        <outline text="Cardiolipin supports respiratory complexes">
          <outline text="Defects: cardiomyopathy, myopathy, neutropenia"/>
        </outline>
        <outline text="Sphingolipids built on ceramide">
          <outline text="Sphingomyelin, glycosphingolipids, gangliosides"/>
          <outline text="Missing hydrolases cause storage disorders"/>
        </outline>
        <outline text="Composition sets fluidity and permeability">
          <outline text="Cholesterol buffers fluidity"/>
        </outline>
        <outline text="Leaflet asymmetry actively maintained">
          <outline text="External phosphatidylserine marks apoptosis"/>
        </outline>
      </outline>
      <outline text="Lipid signalling">
        <outline text="Phospholipase C splits phosphoinositide bisphosphate">
          <outline text="Diacylglycerol and inositol trisphosphate"/>
          <outline text="Protein kinase C and calcium release"/>
        </outline>
        <outline text="Phospholipase A2 releases arachidonic acid"/>
        <outline text="Phosphoinositide 3-kinase recruits Akt"/>
        <outline text="Eicosanoids from arachidonic acid">
          <outline text="Cyclooxygenases: prostaglandins, thromboxanes"/>
          <outline text="Lipoxygenases: leukotrienes, lipoxins"/>
          <outline text="NSAIDs, glucocorticoids, leukotriene modifiers"/>
        </outline>
      </outline>
      <outline text="Cholesterol synthesis and fate">
        <outline text="HMG-CoA reductase makes mevalonate">
          <outline text="Isoprenes, squalene, lanosterol"/>
          <outline text="Isoprenoids prenylate signalling proteins"/>
        </outline>
        <outline text="SREBP responds to low sterol">
          <outline text="Moves to Golgi for activating cleavage"/>
        </outline>
        <outline text="Statins raise LDL receptors"/>
        <outline text="Ring cannot be degraded">
          <outline text="Excreted as biliary cholesterol and bile acids"/>
        </outline>
      </outline>
      <outline text="Lipoprotein particles">
        <outline text="Phospholipid surface around hydrophobic core"/>
        <outline text="Chylomicrons, VLDL, LDL, HDL roles"/>
        <outline text="Apolipoprotein B counts atherogenic particles">
          <outline text="One B-48 or B-100 per particle"/>
        </outline>
        <outline text="C-II activates lipoprotein lipase"/>
        <outline text="E supports remnant uptake"/>
        <outline text="VLDL becomes IDL then LDL">
          <outline text="Receptor defects raise LDL markedly"/>
        </outline>
        <outline text="HDL accepts cellular cholesterol">
          <outline text="Lecithin-cholesterol acyltransferase"/>
          <outline text="Raising HDL cholesterol not reliably beneficial"/>
        </outline>
      </outline>
      <outline text="Dyslipidaemia and atherosclerosis">
        <outline text="Lipase or C-II deficiency: chylomicronaemia">
          <outline text="Pancreatitis risk"/>
        </outline>
        <outline text="Secondary factors modify triglycerides"/>
        <outline text="Atherosclerosis starts with apoB retention">
          <outline text="Foam cells, plaque, cap disruption"/>
        </outline>
        <outline text="LDL cholesterol versus apoB discordance"/>
        <outline text="Lipoprotein(a) largely inherited">
          <outline text="Atherosclerotic and calcific-valve risk"/>
        </outline>
      </outline>
      <outline text="Lipotoxicity and steatosis">
        <outline text="Lipid droplets buffer toxic lipids">
          <outline text="Overflow: diacylglycerols, ceramides"/>
        </outline>
        <outline text="Steatosis: uptake and synthesis exceed disposal">
          <outline text="Choline deficiency impairs export"/>
        </outline>
        <outline text="Risk depends on lipid, particle, tissue, time"/>
      </outline>
    </outline>
  </body>
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