Please confirm topic selection

Are you sure you want to trigger topic in your Anconeus AI algorithm?

Please confirm action

You are done for today with this topic.

Would you like to start learning session with this topic items scheduled for future?

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
Card
1 of 0
Question
1 of 5
Private Note