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  <head>
    <title>090-01 Protein turnover, amino-acid catabolism, ammonia transport, and the urea cycle</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Protein turnover, amino-acid catabolism, and the urea cycle">
      <outline text="Protein turnover and balance">
        <outline text="No inert storage depot for amino acids">
          <outline text="Nitrogen excreted, carbon to shared pathways"/>
        </outline>
        <outline text="Proteasome: short-lived, regulatory, abnormal proteins"/>
        <outline text="Autophagy-lysosome: long-lived, aggregates, organelles"/>
        <outline text="Positive in growth, pregnancy, recovery"/>
        <outline text="Negative in starvation, illness, trauma, immobility"/>
        <outline text="Nitrogen balance misses unmeasured routes">
          <outline text="Stable muscle mass can hide altered turnover"/>
        </outline>
      </outline>
      <outline text="Digestion and absorption">
        <outline text="Gastric acid denatures, pepsin cleaves"/>
        <outline text="Pancreatic zymogens activated in small intestine">
          <outline text="Enteropeptidase initiates trypsin"/>
          <outline text="Trypsin activates other enzymes"/>
        </outline>
        <outline text="Brush-border and intracellular peptidases finish"/>
        <outline text="Sodium- or proton-coupled uptake to portal blood"/>
        <outline text="Transporter defects hit intestine, kidney, or both">
          <outline text="Neutral amino-acid loss: pellagra-like features"/>
          <outline text="Cystine and dibasic loss: cystine stones"/>
        </outline>
      </outline>
      <outline text="Transamination and deamination">
        <outline text="Amino group moved to alpha-ketoglutarate">
          <outline text="Forms glutamate and an alpha-ketoacid"/>
          <outline text="Pyridoxal phosphate carries the amino group"/>
        </outline>
        <outline text="Alanine aminotransferase relatively liver enriched"/>
        <outline text="Aspartate aminotransferase in liver, muscle, heart">
          <outline text="Plasma activity shows leakage, not function"/>
        </outline>
        <outline text="Glutamate as central nitrogen collector">
          <outline text="Glutamate dehydrogenase releases free ammonia"/>
          <outline text="Regulated by energy-state nucleotides"/>
        </outline>
        <outline text="Transdeamination: transfer, then deamination"/>
      </outline>
      <outline text="Ammonia transport">
        <outline text="Free ammonia is toxic to brain"/>
        <outline text="Glutamine synthetase fixes ammonia using ATP"/>
        <outline text="Liver and kidney glutaminase release ammonia">
          <outline text="For urea synthesis or urinary buffering"/>
        </outline>
        <outline text="Gut ammonia reaches liver via portal blood"/>
        <outline text="Glucose-alanine cycle from muscle">
          <outline text="Supports glucose but costs muscle protein"/>
        </outline>
        <outline text="Glutamine fuels gut, immune cells, kidney"/>
      </outline>
      <outline text="Urea cycle">
        <outline text="Spans mitochondrial matrix and cytosol"/>
        <outline text="Nitrogen from ammonia and aspartate"/>
        <outline text="Three ATP, four high-energy bonds"/>
        <outline text="Carbamoyl-phosphate synthetase one">
          <outline text="N-acetylglutamate is obligatory activator"/>
          <outline text="Arginine and amino-acid load raise it"/>
        </outline>
        <outline text="Ornithine transcarbamylase forms citrulline"/>
        <outline text="Argininosuccinate synthetase adds aspartate"/>
        <outline text="Lyase yields arginine and fumarate"/>
        <outline text="Arginase releases urea and ornithine"/>
        <outline text="Fumarate links to citric-acid metabolism">
          <outline text="Aspartate-argininosuccinate shunt"/>
        </outline>
        <outline text="Urea excreted mainly by kidney"/>
      </outline>
      <outline text="Urea-cycle defects">
        <outline text="Hyperammonaemia after protein, illness, fasting">
          <outline text="Vomiting, confusion, seizures, coma"/>
          <outline text="Early respiratory alkalosis"/>
        </outline>
        <outline text="Neonates first normal after maternal clearance"/>
        <outline text="Ornithine-transcarbamylase deficiency is X-linked">
          <outline text="Variable X inactivation in females"/>
          <outline text="Carbamoyl phosphate spills, orotic acid rises"/>
        </outline>
        <outline text="Proximal defects: no similar orotic acid rise"/>
        <outline text="Arginase deficiency: chronic spasticity">
          <outline text="Ammonia rise may be milder"/>
        </outline>
        <outline text="Interpret by age, feeding, treatment, timing"/>
      </outline>
      <outline text="Management and brain injury">
        <outline text="Stop protein briefly"/>
        <outline text="Glucose and lipid reverse catabolism"/>
        <outline text="Nitrogen scavengers form excretable conjugates"/>
        <outline text="Dialysis for severe levels or encephalopathy"/>
        <outline text="Long term: protein for growth, avoid excess"/>
        <outline text="Astrocyte glutamine causes osmotic stress">
          <outline text="Transmitter pools, mitochondria, blood flow disturbed"/>
        </outline>
        <outline text="Plasma level correlates imperfectly with symptoms"/>
      </outline>
      <outline text="Liver, kidney, and sampling">
        <outline text="Hepatic encephalopathy differs from inherited defects">
          <outline text="Portal shunting, inflammation, drugs, electrolytes"/>
          <outline text="Normal ammonia does not exclude it"/>
        </outline>
        <outline text="Kidney makes ammonium and bicarbonate from glutamine">
          <outline text="Acidosis increases renal glutamine use"/>
          <outline text="Urinary ammonium is adaptive acid excretion"/>
        </outline>
        <outline text="Warm or delayed samples raise ammonia">
          <outline text="Repeat promptly, but treat if delay is unsafe"/>
        </outline>
      </outline>
      <outline text="Carbon skeletons">
        <outline text="Glucogenic, ketogenic, or both"/>
        <outline text="Leucine and lysine exclusively ketogenic"/>
        <outline text="Fate set by hormones, tissue, demand"/>
        <outline text="Branched-chain transamination mainly in muscle">
          <outline text="Thiamine-dependent decarboxylation complex"/>
          <outline text="Defect: maple-syrup-urine disease"/>
          <outline text="Limit branched substrates, preserve growth"/>
        </outline>
      </outline>
    </outline>
  </body>
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