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Overview
  •  Purine
    • salvage pathway
      • see figure
    • clinical importance
      • adenosine deaminase (ADA) deficiency 
        • defective purine salvage
          • results in excess ATP and dATP
        • prevents DNA synthesis
          • ATP and dATP feedback negatively on ribonucleotide reductase in the synthesis of purines and pyrimidines for DNA replication
          • ↓ lymphocyte count
            • major cause of SCID (severe combined immunodeficiency disease)
              • lack of both T and B cells
        • AR
      • Lesch-Nyhan disease
        • defective purine salvage
        • lacks hypoxanthine guanine phosphoribosyl pyrophosphate transferase (HGPRT) enzyme
        • XR
        • presentation
          • severe CNS symptoms
            • choreoathetosis
            • mental retardation
          • self-mutilation
          • hyperuricemia
            • degradation of all purines since it cannot salvage
      • gout
        • pathophysiology
          • high urate levels due to
            • ↑ in cell breakdown
              • e.g. treatment of large tumor masses with radiation or chemo
            • ↓ in renal excretion (most common cause)
          • results in precipitation of monosodium urate crystals in joints
            • negative birefringence
              • yellow when parallel to slow ray
            • needle shaped
        • presentation
          • recurrent acute arthritis
            • pain in big toe first (podagra)
          • chronic
            • tophi present
              • granulomatous deposition (multinucleated giant cells) of crystals in soft tissue
          • ↑ frequency in men >30 y/o
        • treatment
          • acute → colchicine or indomethacin
          • chronic due to ↓ in renal excretion → probenecid
          • chronic due to ↑ in cell breakdown → allopurinol
  • Pyrimidine
    • salvage
      • may be salvaged by pyrimidine salvage enzymes
    • degradation
      • completely broken down to ammonia
  • Other causes of hyperuricemia
    • ↑ EtOH intake
      • can precipitate an acute gout attack
    • ↑ nucleic acid in diet
      • red meats, organ meats
    • phosphate "trapping" diseases
      • e.g. glucose-6-phosphate deficiency (G6PD), galactose uridyltransferase deficiency
      • caused by an inability to dephosphorylate common metabolites and therefore leads to trapping of phosphate by these metabolites
      • lack of phosphate prevents synthesis of ATP, GTP, plus other nucleotide phosphates
      • ADP. AMP, and other hypophosphorylated bases are salvaged producing uric acid
 

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