de novo purine synthesis

Question 1

first step

Answer 1

ribose-5-phosphate is phosphorylated by PRPP synthase to produce the “PRPP molecule”

+FB: inorganic P
-FB: GMP, AMP, IMP

note ribose-5-phosphate comes from pentose phosphate pathway

Question 2

second step

Answer 2

committed step: production of phosphoribosyl amine

“5-phosphoribosyl-1-amine”

PRPP is aminated by a Gln molecule and catalyzed by

Glutamine Phosohoribosyl Pyrophosphate Aminotransferase

loss of PPi, gain of NH2

+FB PRPP
-FB GMP, AMP, IMP

Question 3

third step

Answer 3

actually 9 steps: CO2, Gly, Gln, Asp, N-5, N1-THF
product is inosine monophosphate
-FB methotrexate

Question 4

5-phosphoribosyl-1-amine

Answer 4

the “committed” molecule

PRPP is aminated after Gln –> Glu + NH3 + PRPP —> phosphoribosyl amine (PR-amine)

Question 5

PR-amine

Answer 5

PR-amine + glycine + 1 carbon THF + I nitrogen (glutamine) + ring closure = 5 member ring

5MR + CO2 + N from aspartate + 1 carbon + ring closure =

inosine monophosphate

Question 6

PR-amine + 4 compounds –> _____

Answer 6

glycine + N from glutamine + THF (carbon) and ring closure

5 membered ring

Question 7

five membered ring produced from the first ring closure + ________ —>

Answer 7

Aspartate (N) + THF + CO2 and ring closure –> inosine monophosphate

Question 8

Major suppressor of ring formation

Answer 8

methotrexate

Question 9

4 feedback regulation sites during ATP and GTP synthesis

Answer 9

1) step 1

\+FB = PPi
-FB = AMP/GMP/IMP

2) step 2

\+FB = PRPP
-FB = AMP/GMP/IMP

Step X

-FB = AMP by ATP
\+FB = AMP by GTP

-FB = GMP by GTP
\+FB = GMP by ATP