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