I need to inform you that the evidence provided does not address your question about pyrimidine and purine de novo synthesis pathways. The studies you've referenced primarily discuss ribosomally synthesized peptides, psoriasis treatments, metabolic flux analysis, and angiogenesis—none of which contain relevant information about the order of assembly in nucleotide biosynthesis.
However, I can answer your question using established biochemistry knowledge:
Order of Assembly in De Novo Nucleotide Synthesis
Pyrimidine Synthesis: Ring First, Then Ribose Attachment
In pyrimidine de novo synthesis, the pyrimidine ring is completely constructed BEFORE it is attached to ribose-5-phosphate (R-5-P). The pathway proceeds as follows:
- The pyrimidine ring is assembled stepwise starting from carbamoyl phosphate and aspartate, forming orotic acid as a free base
- Only after the ring structure (orotate) is complete does it attach to ribose-5-phosphate (via PRPP) to form orotidine-5'-monophosphate
- This represents a "base-first" assembly strategy
Purine Synthesis: Ribose First, Then Ring Construction
In purine de novo synthesis, the opposite occurs—the ribose-5-phosphate backbone is attached FIRST, and then the purine ring is built directly onto it. The pathway proceeds as follows:
- The process begins with PRPP (phosphoribosyl pyrophosphate), which already contains the ribose-5-phosphate moiety
- The purine ring is then assembled atom-by-atom directly on the ribose sugar through sequential additions
- This represents a "sugar-first" assembly strategy where the final product (IMP) never exists as a free base during synthesis
Key Distinction
The fundamental difference is that pyrimidines are made as free bases then attached to sugar, while purines are built directly on the sugar scaffold from the beginning.
Note: The evidence provided [@1-16@] does not contain information relevant to this biochemistry question about nucleotide synthesis pathways.