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  <head>
    <title>088-01 Glycolysis, pyruvate metabolism, gluconeogenesis, and reciprocal glucose control</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Glycolysis, pyruvate, gluconeogenesis, reciprocal control">
      <outline text="Purpose and glucose entry">
        <outline text="Supplies ATP, intermediates, reducing power, fuel"/>
        <outline text="Shared reversible reactions, distinct bypass enzymes">
          <outline text="Reciprocal control, not wasteful cycling"/>
        </outline>
        <outline text="Facilitative or sodium-coupled transporters"/>
        <outline text="Insulin recruits GLUT4 to muscle and adipose"/>
        <outline text="Brain uptake largely insulin independent"/>
        <outline text="Erythrocytes lack mitochondria, depend on glucose"/>
      </outline>
      <outline text="Trapping and the committed step">
        <outline text="Hexokinase forms glucose six-phosphate">
          <outline text="Charged sugar phosphate cannot diffuse out"/>
          <outline text="Most hexokinases high affinity, product inhibited"/>
        </outline>
        <outline text="Hepatic glucokinase low affinity, high capacity">
          <outline text="Not inhibited by glucose six-phosphate"/>
          <outline text="Sequestration and insulin-dependent expression"/>
          <outline text="Liver buffers postprandial glucose"/>
        </outline>
        <outline text="Phosphofructokinase one: committed step">
          <outline text="AMP and fructose 2,6-bisphosphate accelerate"/>
          <outline text="ATP, citrate, muscle acidity slow"/>
        </outline>
      </outline>
      <outline text="Energy yield and lactate">
        <outline text="Aldolase and triose-phosphate isomerase">
          <outline text="Both fragments continue as G3P"/>
        </outline>
        <outline text="G3P dehydrogenase makes NADH"/>
        <outline text="Phosphoglycerate kinase: first substrate-level ATP"/>
        <outline text="Pyruvate kinase uses PEP transfer potential"/>
        <outline text="Net two ATP, two NADH, two pyruvate"/>
        <outline text="NAD plus regeneration needed to continue">
          <outline text="Lactate dehydrogenase oxidises NADH"/>
        </outline>
        <outline text="Lactate is shuttled fuel, not waste">
          <outline text="Heart and oxidative muscle consume it"/>
          <outline text="Rise does not prove tissue hypoxia"/>
        </outline>
      </outline>
      <outline text="Pyruvate fates and dehydrogenase">
        <outline text="Lactate dehydrogenase and alanine aminotransferase"/>
        <outline text="Pyruvate carboxylase makes oxaloacetate"/>
        <outline text="Pyruvate dehydrogenase makes acetyl-CoA irreversibly">
          <outline text="Needs thiamine pyrophosphate, lipoate, CoA, FAD, NAD"/>
          <outline text="Inhibited by products, kinase, high energy"/>
          <outline text="Promoted by phosphatase, pyruvate, demand"/>
        </outline>
        <outline text="Deficiency diverts pyruvate to lactate, alanine">
          <outline text="Brain particularly harmed"/>
          <outline text="Thiamine deficiency: functional block"/>
        </outline>
        <outline text="No net glucose from acetyl-CoA"/>
      </outline>
      <outline text="Gluconeogenic bypasses">
        <outline text="Liver mainly, kidney in prolonged fasting"/>
        <outline text="Lactate, amino acids, glycerol, propionate">
          <outline text="Even-chain fatty acids give no net carbon"/>
        </outline>
        <outline text="Pyruvate carboxylase: biotin, CO2, ATP">
          <outline text="Activated by acetyl-CoA"/>
          <outline text="Oxaloacetate exits as malate or aspartate"/>
        </outline>
        <outline text="PEP carboxykinase uses GTP">
          <outline text="Decarboxylation drives the reversal"/>
        </outline>
        <outline text="Fructose-1,6-bisphosphatase bypasses PFK">
          <outline text="Inhibited by AMP, fructose 2,6-bisphosphate"/>
        </outline>
        <outline text="Glucose-6-phosphatase releases free glucose">
          <outline text="Muscle lacks it, keeps glucose six-phosphate"/>
        </outline>
      </outline>
      <outline text="Hormonal switching">
        <outline text="Bifunctional enzyme sets fructose 2,6-bisphosphate">
          <outline text="Glucagon, cAMP, PKA lower it"/>
          <outline text="Glycolysis slows, gluconeogenesis favoured"/>
        </outline>
        <outline text="Hepatic pyruvate kinase phosphorylated in fasting">
          <outline text="Prevents PEP recycling to pyruvate"/>
          <outline text="Fructose 1,6-bisphosphate feed-forward activates"/>
        </outline>
        <outline text="Erythrocyte pyruvate-kinase deficiency">
          <outline text="Low ATP, membrane failure, haemolysis"/>
        </outline>
        <outline text="Insulin induces glycolytic enzymes in fed state"/>
        <outline text="Glucagon raises gluconeogenesis in fasting"/>
      </outline>
      <outline text="Interorgan cycles and substrate supply">
        <outline text="Cori cycle returns lactate to liver"/>
        <outline text="Glucose-alanine cycle carries carbon and nitrogen">
          <outline text="Nitrogen becomes urea"/>
        </outline>
        <outline text="Cycles redistribute burden, create no energy"/>
        <outline text="Fatty-acid oxidation inhibits pyruvate oxidation"/>
        <outline text="Ethanol NADH diverts pyruvate and oxaloacetate">
          <outline text="Fasting hypoglycaemia with lactic acidosis"/>
        </outline>
      </outline>
      <outline text="Other sugars and glucose balance">
        <outline text="Fructose enters below phosphofructokinase"/>
        <outline text="Galactose becomes glucose one-phosphate"/>
        <outline text="Inherited defects cause toxic accumulation"/>
        <outline text="Hypoglycaemia from insulin excess or failed output"/>
        <outline text="Hyperglycaemia: high hepatic output persists"/>
        <outline text="Renal cortex couples glucose and ammonium"/>
        <outline text="Disease when one tissue burdens another"/>
      </outline>
    </outline>
  </body>
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