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  <head>
    <title>088-03 Glycogen, pentose-phosphate pathway, NADPH, and integrated carbohydrate control</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Glycogen, pentose phosphate, NADPH, integration">
      <outline text="Glycogen structure and synthesis">
        <outline text="Alpha 1-4 chains with alpha 1-6 branches"/>
        <outline text="Glycogenin primes synthesis"/>
        <outline text="Branches create many nonreducing ends">
          <outline text="Simultaneous synthesis or breakdown"/>
          <outline text="Greater solubility"/>
        </outline>
        <outline text="Liver buffers blood, muscle fuels contraction"/>
        <outline text="Phosphoglucomutase makes glucose 1-phosphate"/>
        <outline text="UTP activates to UDP-glucose"/>
        <outline text="Glycogen synthase adds alpha 1-4 links"/>
        <outline text="Branching enzyme creates alpha 1-6 links"/>
      </outline>
      <outline text="Glycogen breakdown">
        <outline text="Phosphorylase uses inorganic phosphate">
          <outline text="Conserves energy versus hydrolysis"/>
        </outline>
        <outline text="Stops near branches">
          <outline text="Debranching enzyme transfers, then hydrolyses"/>
          <outline text="Small amount of free glucose"/>
        </outline>
        <outline text="Liver glucose-6-phosphatase exports glucose"/>
        <outline text="Muscle lacks it, feeds glycolysis"/>
        <outline text="Stored with water, depletion shifts mass"/>
      </outline>
      <outline text="Hormonal and allosteric control">
        <outline text="Synthase active when dephosphorylated">
          <outline text="Glucose six-phosphate stimulates"/>
          <outline text="Insulin activates phosphatases"/>
        </outline>
        <outline text="Glucagon acts on liver, not muscle">
          <outline text="cAMP and PKA activate phosphorylase"/>
          <outline text="Synthase inhibited"/>
        </outline>
        <outline text="Epinephrine acts on liver and muscle"/>
        <outline text="Contraction calcium via calmodulin">
          <outline text="Activates phosphorylase kinase"/>
        </outline>
        <outline text="Muscle phosphorylase: AMP on, ATP off"/>
        <outline text="Liver phosphorylase responds to glucose"/>
        <outline text="Reciprocal phosphorylation limits cycling"/>
      </outline>
      <outline text="Glycogen-storage disorders">
        <outline text="Hepatic: fasting hypoglycaemia, hepatomegaly"/>
        <outline text="Lysosomal: cardiomyopathy, myopathy"/>
        <outline text="Muscle: exercise intolerance, cramps">
          <outline text="Rhabdomyolysis"/>
        </outline>
        <outline text="Abnormal branching: insoluble polymer"/>
      </outline>
      <outline text="Pentose-phosphate pathway">
        <outline text="Cytosolic, oxidative and nonoxidative phases"/>
        <outline text="Oxidative phase starts with G6PD">
          <outline text="Two NADPH, CO2, ribulose 5-phosphate"/>
          <outline text="Irreversible, driven by NADP plus"/>
        </outline>
        <outline text="Nonoxidative phase interconverts sugars">
          <outline text="Transketolase moves two carbons, needs TPP"/>
          <outline text="Transaldolase moves three carbons"/>
          <outline text="Ribose 5-phosphate for nucleotides"/>
        </outline>
        <outline text="Adapts to NADPH versus ribose need">
          <outline text="NADPH need: recycle pentoses, lose CO2"/>
        </outline>
      </outline>
      <outline text="NADPH roles and deficiencies">
        <outline text="Glutathione, lipid synthesis, P450, NO"/>
        <outline text="Distinct from energy-carrying NADH"/>
        <outline text="Erythrocytes rely on it for glutathione">
          <outline text="G6PD deficiency: episodic haemolysis"/>
          <outline text="Infection, drugs, oxidant foods trigger"/>
          <outline text="X-linked, variable severity"/>
        </outline>
        <outline text="Phagocyte NADPH oxidase makes superoxide">
          <outline text="Defect: chronic granulomatous disease"/>
        </outline>
        <outline text="Glucuronic acid for conjugation">
          <outline text="Humans cannot make vitamin C"/>
        </outline>
      </outline>
      <outline text="Fed, fasting, and exercise states">
        <outline text="Fed liver: glycogen, NADPH, fatty acids"/>
        <outline text="Adipose makes glycerol-3-phosphate"/>
        <outline text="Early fasting: hepatic glycogenolysis"/>
        <outline text="Later: gluconeogenesis, kidney rises">
          <outline text="Brain shifts to ketone bodies"/>
          <outline text="Erythrocytes remain glycolytic"/>
        </outline>
        <outline text="Exercise: insulin-independent uptake"/>
        <outline text="After exercise: glycogen replenished"/>
      </outline>
      <outline text="Hyperglycaemic injury">
        <outline text="Insufficient insulin raises harmful flux"/>
        <outline text="Polyol pathway makes sorbitol with NADPH">
          <outline text="Osmotic and redox stress"/>
          <outline text="Lens, nerve, retina, kidney"/>
        </outline>
        <outline text="Advanced glycation cross-links proteins">
          <outline text="Stiffens matrix, triggers inflammation"/>
        </outline>
        <outline text="Glycated haemoglobin tracks exposure">
          <outline text="Distorted by red-cell turnover, variants"/>
        </outline>
      </outline>
      <outline text="Timescales and interpretation">
        <outline text="Allosteric immediate, phosphorylation minutes"/>
        <outline text="Transcription over hours to days"/>
        <outline text="Snapshot reflects several histories"/>
        <outline text="Concentration differs from flux"/>
        <outline text="Disease when a branch cannot respond"/>
      </outline>
    </outline>
  </body>
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