Purine Nucleotides

Question 1

Lesch-Nyhan Syndrome

Answer 1

genetic disorder assoc w/ deficiency is hypoxanthinine-guanine phosphoribotransferase (HGPRT); used for salvage of free purine base

Question 2

how are free purine bases salvaged?

Answer 2

PRPP-dependent phosphoribosyltransferases

Question 3

what is needed for synthesis of purines de novo?

Answer 3

glutamine
glycine
N10-formyl-THF
CO2
aspartate

Question 4

regulatory site of purine synthesis

Answer 4

(1) PRPP synthetase / ribose phosphate pyrophosphokinase - not a committing step
(2) PRPP amidotransferase (glutamine;phosphoribosyl pyrophosphate amidotransferase) - 1st step in committed purine synth pathway

Question 5

what is the end product of the de novo purine synthesis pathway, and what can it be converted to

Answer 5

IMP, can be converted to AMP and GMP

Question 6

what causes gout?

Answer 6

excessive production or poor renal excretion of uric acid - could be caused by

(1) mutations in PRPP synthase
(2) Lesch-Nyhan syndrome - loss of HGPRT activity
(3) impaired kidney excretion or compromised kidney function

Question 7

regulation of PRPP synthetase

Answer 7

+: Pi

-: purine ribonucleotides

Question 8

regulation of amidotransferase

Answer 8

key regulatory point, first committed step in de novo purine biosynth
+: PRPP
-: AMP, GMP, IMP

Question 9

xanthine oxidase

Answer 9

critical for conversion of purines to uric acid (for degradation of purine bases so they can be excreted)

Question 10

how to treat gout? why does this treatment work

Answer 10

Allopurinol

• reduces uric acid synthesis at xanthine oxidase
• increased nucleotides, inhibits de novo pathway