Which enzyme catalyzes the first committed step of de novo purine synthesis, and what is the product of this reaction?

Explanation

## De Novo Purine Synthesis — First Committed Step **Key Point:** PRPP amidotransferase (also called amidophosphoribosyltransferase) catalyzes the first committed step of de novo purine synthesis, converting PRPP (5-phosphoribosyl-1-pyrophosphate) to 5-phosphoribosyl-1-amine. ### Enzyme Details | Feature | PRPP Amidotransferase | | --- | --- | | Substrate | PRPP (activated ribose) | | Product | 5-phosphoribosyl-1-amine | | Cofactor | Glutamine (NH~2~ donor) | | Regulation | Feedback inhibited by AMP, GMP, IMP | | Location | Cytoplasm | ### Why This Step Is "First Committed" 1. **PRPP is a branch point** — it is also used in salvage pathways (HGPRT, APRT) and pyrimidine synthesis. 2. **Once 5-phosphoribosyl-1-amine is formed**, the pathway is committed to purine synthesis — it cannot be diverted to other pathways. 3. **This is the rate-limiting step** of de novo purine synthesis and the primary site of allosteric feedback regulation. **High-Yield:** PRPP amidotransferase is the target of feedback inhibition by purine nucleotides (AMP, GMP, IMP). This is why hyperuricemia and gout can be worsened by high purine intake — excess purines suppress this enzyme, but salvage pathways still generate more purines. **Clinical Pearl:** Deficiency of HGPRT (hypoxanthine-guanine phosphoribosyltransferase) leads to Lesch-Nyhan syndrome because salvage is blocked, forcing all purines through de novo synthesis, causing massive hyperuricemia and gout in childhood. ### Clarification of Distractors - **PRPP synthetase** catalyzes the formation of PRPP itself from ribose-5-phosphate and ATP — this is a pre-committed step, not the first committed step. - **Adenosine deaminase** is a salvage pathway enzyme, not part of de novo synthesis. - **Phosphoribosylpyrophosphate synthetase** is another name for PRPP synthetase, not amidotransferase.