Chapter 18: Purine and Pyrimidine Metabolism (continued) Flashcards
What is the inheritance pattern of ADA deficiency?
AR
ADA stands for what?
adenosine deaminase
What is a disorder caused by ADA deficiency? Explain.
SCID (severe combined immunodeficiency) which causes lack of both B-cell and T-cell function
What are some organisms that children with SCID are prone to contract?
pneumocystis carinii, candida
What are some treatments for ADA deficiency?
enzyme replacement therapy and bone marrow transplantation
Pathology of ADA deficiency.
high levels of dATP accumulate in red cells of ADA patients and inhibit ribonucleotide reductase, thereby inhibiting the production of other essential deoxynucleotide precursors for DNA synthesis
What is the causes of tumor lysis syndrome?
excessive uric acid is cause by the destruction of the cancer cell’s nucleic acid into purines undergoing turnover
2 general ways hyperuricemia is caused?
overproduction of uric acid or underexcretion of uric acid by the kidneys
The crystals in gout?
monosodium urate crystals
What are the MOA by which allopurinol helps reduce excess uric acid in the body?
inhibits xanthine oxidase and also reduces purine synthesis by inhibiting PRPP amidotransferase provided HGPRT is active
Hyperuricemia and gout commonly accompany which conditions?
- lesch-nyhan syndrome (no purine salvage)
- partial deficiency of HGPRT
- alcoholism (lactate and urate compete for same transport system in the kidney)
- glucose 6-phosphatase deficiency
- hereditary fructose intolerance (aldolase B deficiency)
- galactose 1- phosphate uridyl transferase deficiency (galactosemia)
- mutations in PRPP synthetase that lower Km
How does galactose 1-phosphate uridyl transferase deficiency and mutations in PRPP synthetase that lower Km cause hyperuricemia?
phosphorylated sugars accumulate, decreasing the available Pi and increasing AMP (which cannot be phosphorylated to ADP and ATP). The excess AMP is converted to uric acid
Inheritance pattern of Lesch-Nyhan syndrome?
X-linked recessive
MOA of febuxostat?
non-purine inhibitor of xanthine oxidase
There are large number of known mutations in the HGPRT gene. These have varying effects on the Km for the enzyme product, generating varying degrees of severity. What is this an example of in genetics?
allelic herterogeneity
