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Updated: Aug 4 2020

Nucleotide Catabolism/Salvage

  • 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
            • responsible for phosphoribosyl group transfer
          • X-linked recessive
          • 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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