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
QUESTIONS 1 of 5 1 2 3 4 5 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.BC.14.1) A 3-year-old male was brought to the pediatrician with severe lip lacerations, with a portion of his tongue appearing to be bitten off, as well as missing portions of the fingers on his right hand. A family history is notable for two similar cases in male cousins on the mother's side. A urinalysis revealed a high level of uric acid. Which of the following is the mode of inheritance for this disorder? QID: 106253 Type & Select Correct Answer 1 X-linked recessive 62% (53/85) 2 X-linked dominant 5% (4/85) 3 Autosomal dominant 6% (5/85) 4 Autosomal recessvie 13% (11/85) 5 Maternally inherited mitochondrial defect 6% (5/85) M 2 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic (M1.BC.13.1) A six-month-old infant presents with chronic, persistent diarrhea, oral thrush, and a severe diaper rash. The infant was treated four weeks ago for an upper respiratory and ear infection. A family history is significant for a consanguineous relationship between the mother and father. Physical examination demonstrates the absence of palpable lymph nodes. Accumulation of which of the following would lead to this disease phenotype? QID: 106240 Type & Select Correct Answer 1 Deoxyadenosine 57% (241/420) 2 Phenylalanine 11% (46/420) 3 Galactitol 6% (26/420) 4 Ceramide trihexoside 12% (52/420) 5 Sphingomyelin 10% (41/420) M 2 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK
All Videos (1) Login to View Community Videos Login to View Community Videos Lesch-Nyhan Syndrome Luigi Bonini Biochemistry - Nucleotide Catabolism/Salvage D 2/2/2016 232 views 5.0 (2) Biochemistry | Nucleotide Catabolism/Salvage Biochemistry - Nucleotide Catabolism/Salvage Listen Now 10:48 min 12/9/2021 38 plays 3.0 (1)