De novo synthesis of purines

Sources of carbon and nitrogen atoms in purine ring:

Fig. 31. Sources of carbon and nitrogen in purine ring (Stryer's Biochemistry 5^th ed)

General features:

1. Unlike pyrimidines that do not acquire the ribose until the base moiety is synthesized, purine ring is assembled on PRPP.

2. IMP is synthesized first and serves as a precursor to adenine and guanine nucleotides.

Step 1: Formation of 5-phosphoribosyl-1-amine from PRPP (committed step) by the action of glutamine phosphoribosyl amidotransferase. PRPP provides the foundation for purine biosynthesis. Glutamine phosphoribosyl amidotransferase has two domains: one hydrolyzes glutamine to ammonia, and the other one is phosphoribosyl transferase domain. Ammonia is channeled to site II without leaving the enzyme.

This is the committed step. It is feedback inhibited by IMP. GMP, AMP