【多选题】How do cells construct the purine ring of inosinate (IMP) during d e novo synthesis of purine nucleotides?
A.
In the first committed step of the pathway, an amino group donated by glutamine is attached at C-1 of PRPP. The resulting 5-phosphoribosylamine is highly unstable, with a half-life of 30 seconds at pH 7.5. The purine ring is subsequently built up on this structure.
B.
The second step is the addition of three atoms from glycine. An ATP is consumed to activate the glycine carboxyl group (in the form of an acyl phosphate) for this condensation reaction. The added glycine amino group is then formylated by N 10 -formyltetrahydrofolate, and a nitrogen is contributed by glutamine, before dehydration and ring closure yield the five-membered imidazole ring of the purine nucleus, as 5-aminoimidazole ribonucleotide.
C.
At this point, three of the six atoms needed for the second ring in the purine structure are in place. To complete the process, a carboxyl group is first added. This carboxylation is unusual in that it does not require biotin, but instead uses the bicarbonate generally present in aqueous solutions. A rearrangement transfers the carboxylate from the exocyclic amino group to position 4 of the imidazole ring. In higher eukaryotes, including humans, the 5-aminoimidazole ribonucleotide product of step 5 is carboxylated directly to carboxyaminoimidazole ribonucleotide in one step instead of two. The enzyme catalyzing this reaction is AIR carboxylase.
D.
Aspartate now donates its amino group in two steps: formation of an amide bond, followed by elimination of the carbon skeleton of aspartate (as fumarate). The final carbon is contributed by N 10 -formyltetrahydrofolate, and a second ring closure takes place to yield the second fused ring of the purine nucleus. The first intermediate with a complete purine ring is inosinate (IMP).