CHM362H5 Lecture Notes - Lecture 26: Phosphofructokinase, Pyrimidine, Purine
Document Summary
Source of atoms in purine rings: origin of atoms in purine synthesis determined by isotope labeling of uric acid in pigeons. Overview of synthesis of purine rings: purine ring is built onto a ribose-5-phosphate platform, 11 enzymatic steps yield inosine monophosphate (imp, amp and gmp are synthesized from imp. Gln: prpp amidotransferase: hexameric enzyme, subject to feedback inhibition by gmp, gdp, gtp, amp, adp, and atp. Inhibition of gln: prpp amidotransferase: azaserine acts as an irreversible inhibitor of glutamine-dependent enzymes, covalently attaches to nucleophilic groups in the glutamine-binding site. Purine synthesis pathway: step 3: addition of atoms from gly to n-9 atom of purine ring, proceeds via 2 steps: Gly coo- group is activated via atp-dependent phosphorylation. Amide bond formation between gly coo- and -amine: pra is hydrolyzed to ribose-5-phosphate and nh3; t1/2 = 5 s at 37 c. Suggests assocaition of amidotransferase and gar synthetase. Step 4: transfer of the formyl group of n10- formyl-tetrahydrofolate (thf) to free.
