Nucleotide Metabolism Flashcards
Lesch-Nyan Syndrome
X-linked
HGPRT deficiency
inability to salvage hypoxanthine & guanine
excess uric acid in urine
orange crystals in baby’s diaper
severe mental retardation, self mutilation, involuntary movments, gout
increased PRPP levels and de novo synthesis
SCIDS - Severe combined immunodeficiency
Adenosine deaminase (ADA) deficiency
guanosine & ionsine pathway preferred
DNA not synthesized in T-cells/B-cells
accumulation of dATP
PNP (Purine nucleoside phosphorylase deficiency)
impairment of T-cell function
decreased uric acid production
increased purine nucleosides and nucleotides
Gout
hyperuricemia
acute arthritic joint inflammation (deposition of uric acid crystals)
monosodium urate crystals
Primary
genetic, affects males over 30
Secondary (number of disorders)
leukemia, polycythemia (increas RBC mass) HGPRT deficiency, antimetabolite treatment of cancer, chronic renal insufficency
Treatment
Cochicine (microtubule inhibitor)
- improvments but no decrease in serum urin acid
- inhibits migration of white cells to joints
Allopurinol
-noncompetitive inhibitor of xanthine oxidase
causes excretion of hypoxanthine and xanthine instead of urate
Orotic aciduria
UMP synthase deficiency
abnormal growth, megaloblastic anemia
excess orotic acid in urine
rare genetic form - missing enzymes
aquired- patients treated for cancer with pyrimidine analog
Treatment
-dietary uridine (absorbed enough to continue pyrimidine nucleotide synthesis)
Mycophenolic Acid
reversible, noncompetitive inhibition of inosine monophosphate dehydrogenase (IMP > GMP)
used to prevent graft rejection
deprives rapidly proliferating T and B cells of key components of nucelic acids
PABA Analogs
-Sulfonamides
inhibits folate synthesis in bacteria (prokaryotes)
-Methotrexate
inhibits folate synthesis in humans
used to treat leukemia
Trimethoprim
inhibits THF synthesis in prokaryotes
Aminopterin
less commonly used than methotrexate
Hydroxyurea
chemotherapy
