ureagenesis disorders Flashcards
ribonucleotide synth starts with?
Ribose 5 phosphate (from PPP) and requires PRPP synthestase
If urea cycle is blocked what is made?
more carbamoyl phosphate and more pyrimidines made
buildup of orotic acid
what is a biproduct of ATP/GTP synthesis?
urate (excreted as uric acid)
where does the amino group added to the PRPP come from?
Glutamine
contributors of C and N in the pathway getting from ribose 5 phosphate?
glutamine 1 Carbon pool (THF) glycine glutamine HCO3 aspartate
negative feedback triggered by
iMP, AMP, GMP prodn allosterically
what enzyme is important for hypoxanthine to xanthine to uric acid prodn
Xanthine oxidase
uric acid accumulates as _______in joints etc and this is bad because it mounts a _____response with recruitment of ____
monosodium urate
inflmmatory
cytokines
how do we preserve purines that may have lost their ribose or phosphate?
HGPRTase
APRTase
HGPRT deficiency from mutation leads to ______, an xlinked genetic disorder with neuro consequences.
Lesch-Nyhan
Causes of Gout
overprodn of uric acid
kidney damage leading to reduced excretion
HGPRTase mutations/decreased activity
PRPP synthetase enzyme loss of allosteric inhibition
What does allopurinol do to treat gout?
looks like a purine and binds to xanthine oxidase to create alloxanthine (hypoxanthine to xanthine to urate)
what type of inhibitor is allopurinol?
suicide
presentation of Lesh-Nyhan
Hyperuricemia Gout Self mutilation retardation dysTonia
what is deficient in Lesch-Nyhan and what is its function?
HGPRTase
this is responsible for converting the hypoxanthine and guanine back into the nucleotides when combined with PRPP. So if you have an HGPRTase deficiency what happens is that the guanine turns into xanthine and the hypoxanthine turns into xanthine via the xanthine oxidase and this leads to increased creation of uric acid. If we block the xanthine oxidase via allopurinol we can disrupt this cycle that will lead to hyperuricemia (gout)
