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Updated: Aug 7 2021

HMP Shunt

  • Overview
    • Function
      • generate NADPH
        • required for FA synthesis, steroid synthesis, reduction of oxidizing agents (H2O2 see figure)
      • provide ribose 5-phosphate
        • required for nucleotide synthesis
    • Pathway
      • occurs in cytoplasm of all cells
      • no ATP consumed or generated
      • 2 phases
        • oxidative
          • produces NADPH
          • glucose 6-phosphate (G6P) → 6-phosphogluconate
            • catalyzed by glucose 6-phosphate dehydrogenase (G6PDH)
              • rate limiting step
              • activated by NADP+, insulin
              • inhibited by NADPH
          • irreversible
        • nonoxidative
          • exchanging intermediate substrates between glycolysis and HMP shunt
            • catalyzed by transketolase
              • requires thiamine
          • reversible
    • Clinical relevance
      • glucose-6-phosphate dehydrogenase (G6PDH) deficiency
        • pathophysiology
          • ↓ NADPH production
            • cells (specifically RBCs) lose protection against oxidizing agents
              • cannot regenerate glutathione
          • XR
          • most common human enzyme deficiency
          • ↑ prevalence among blacks
            • ↑ malarial resistance
              • by shortening the circulation life of RBCs
                • Plasmodium does not have enough time for life span
              • plasmodium does not have defense against free radicals
                • ↑ in free radicals kills parasite
        • presentation
          • episodic hemolytic anemia
            • intravascular hemolysis
            • normocytic
            • 2-3 days post precipitating stress
              • foods
                • fava beans
                  • common in Mediterranean foods
                  • presentation
                    • pallor, hemoglobinuria 24-48 post ingestion
              • drugs
                • sulfonamides, primaquine, antituberculosis drugs
              • infection
                • free radicals generated by the immune system
          • Heinz bodies
            • oxidized hemoglobin that precipitates within RBCs
          • bite cells
            • result from the phagocytic removal of Heinz bodies by macrophages
          • back pain
        • test
          • active hemolysis screen
            • Heinz body prep
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