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  <head>
    <title>089-01 Lipid digestion, fatty-acid transport, mobilisation, and beta oxidation</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Lipid digestion, transport, and beta oxidation">
      <outline text="Why lipids need special handling">
        <outline text="Energy, membranes, signals, steroid precursors"/>
        <outline text="Hydrophobicity demands special transport"/>
        <outline text="Blocked mobilisation or entry causes energy crisis"/>
      </outline>
      <outline text="Digestion and absorption">
        <outline text="Dietary lipid is mainly triacylglycerol"/>
        <outline text="Lingual and gastric lipases: infants, pancreatic failure"/>
        <outline text="Bile salts emulsify fat into droplets">
          <outline text="Amphipathic, made from cholesterol"/>
          <outline text="Recycled via terminal ileum and portal blood"/>
        </outline>
        <outline text="Pancreatic lipase with colipase">
          <outline text="2-monoacylglycerol and free fatty acids"/>
        </outline>
        <outline text="Phospholipase A2 and cholesterol esterase"/>
        <outline text="Mixed micelles cross unstirred water layer"/>
      </outline>
      <outline text="Packaging and export">
        <outline text="Re-esterification in endoplasmic reticulum"/>
        <outline text="Transfer protein loads apolipoprotein B-48">
          <outline text="Chylomicrons exit via lacteals and thoracic duct"/>
          <outline text="Initially bypass the liver"/>
        </outline>
        <outline text="Short and medium chains enter portal blood"/>
        <outline text="Failure causes fat malabsorption">
          <outline text="Fat-soluble-vitamin deficiency"/>
        </outline>
      </outline>
      <outline text="Delivery and mobilisation">
        <outline text="Lipoprotein lipase on capillary endothelium">
          <outline text="Insulin favours adipose activity after meals"/>
          <outline text="Remnants cleared by liver receptors"/>
        </outline>
        <outline text="Adipose lipolysis in fasting and exercise">
          <outline text="Catecholamines and low insulin activate lipases"/>
          <outline text="Insulin suppresses, promotes re-esterification"/>
        </outline>
        <outline text="Glycerol goes to liver">
          <outline text="Adipose has little glycerol kinase"/>
        </outline>
        <outline text="Plasma fatty acids reflect flux, not stores">
          <outline text="Excess: liver fat, insulin resistance"/>
          <outline text="Albumin binding is finite"/>
        </outline>
      </outline>
      <outline text="Activation and mitochondrial entry">
        <outline text="Acyl-CoA synthetase costs two phosphate bonds">
          <outline text="Traps fatty acid for its fate"/>
        </outline>
        <outline text="Carnitine carries acyl groups across inner membrane">
          <outline text="CPT1 on outer membrane"/>
          <outline text="Translocase swaps acylcarnitine for carnitine"/>
          <outline text="CPT2 regenerates acyl-CoA in matrix"/>
        </outline>
        <outline text="Malonyl-CoA inhibits CPT1">
          <outline text="Fed: carboxylase makes malonyl-CoA"/>
          <outline text="Fasting: AMP kinase lowers malonyl-CoA"/>
        </outline>
      </outline>
      <outline text="Beta oxidation and yield">
        <outline text="Four steps remove two carbons per cycle">
          <outline text="FAD dehydrogenation to flavoprotein"/>
          <outline text="Hydration, then NADH dehydrogenation"/>
          <outline text="Thiolysis releases acetyl-CoA"/>
        </outline>
        <outline text="Palmitate: seven cycles, eight acetyl-CoA">
          <outline text="About 106 ATP after activation"/>
        </outline>
        <outline text="More oxygen per ATP than carbohydrate">
          <outline text="Carbohydrate favoured when oxygen limits"/>
        </outline>
        <outline text="Red cells lack mitochondria"/>
        <outline text="Brain uses glucose or ketones"/>
      </outline>
      <outline text="Special fatty acids">
        <outline text="Unsaturated need isomerase, sometimes reductase"/>
        <outline text="Odd chains end as propionyl-CoA">
          <outline text="Biotin carboxylase, B12 mutase"/>
          <outline text="Succinyl-CoA gives limited glucogenic carbon"/>
          <outline text="Defects: organic acidosis, hyperammonaemia"/>
        </outline>
        <outline text="Very-long chains start in peroxisomes">
          <outline text="Electrons to oxygen make hydrogen peroxide"/>
        </outline>
        <outline text="Phytanic acid needs alpha oxidation">
          <outline text="Defects hit retina, nerves, cerebellum"/>
        </outline>
        <outline text="Omega oxidation yields urinary dicarboxylic acids"/>
      </outline>
      <outline text="Oxidation disorders">
        <outline text="MCAD deficiency: hypoketotic hypoglycaemia">
          <outline text="Newborn screening allows fasting avoidance"/>
        </outline>
        <outline text="Primary carnitine deficiency">
          <outline text="Cardiomyopathy, weakness, hypoglycaemia"/>
        </outline>
        <outline text="Carnitine not universally safe or effective"/>
        <outline text="Oxidation fuels hepatic gluconeogenesis">
          <outline text="Acetyl-CoA activates pyruvate carboxylase"/>
          <outline text="Failure: hypoglycaemia with low ketones"/>
        </outline>
      </outline>
      <outline text="Exercise and integrated control">
        <outline text="Moderate prolonged work burns more fat"/>
        <outline text="Intense work relies on carbohydrate"/>
        <outline text="Training raises mitochondria and fat oxidation">
          <outline text="Preserves glycogen"/>
        </outline>
        <outline text="Intramuscular lipid not itself pathological">
          <outline text="Toxicity from diacylglycerols, ceramides"/>
        </outline>
        <outline text="Any blocked boundary mimics fuel scarcity">
          <outline text="Diagnose with timing, ketones, acylcarnitines"/>
        </outline>
      </outline>
    </outline>
  </body>
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