nucleotide synthesis

Meaning: Cells make nucleotides by two routes. De novo synthesis builds them from small molecules (amino acids, CO₂, one-carbon folate units). Salvage recycles free bases and nucleosides released by breakdown, which saves energy. Both routes use PRPP, made from ribose-5-phosphate (supplied by the pentose phosphate pathway) and ATP.

Purines: the ring is assembled step by step on PRPP. Glycine, glutamine, aspartate and folate-carried carbons supply the atoms. The first full nucleotide is IMP, which branches to AMP and GMP.

Pyrimidines: the ring is made first from carbamoyl phosphate and aspartate, forming orotate, and is then attached to PRPP. This gives UMP, and UTP is converted to CTP.

Deoxyribonucleotides: ribonucleotide reductase removes the 2′ hydroxyl from ribonucleoside diphosphates. dTMP comes from dUMP through thymidylate synthase, which needs a folate derivative.

On the MCAT: Passages stress feedback inhibition, in which end products slow early steps so purine and pyrimidine supplies stay balanced. They also ask you to predict that blocking folate use or ribonucleotide reductase lowers DNA synthesis, hitting rapidly dividing cells hardest.

Common confusion: Students mix up the order of assembly. Purines are built on the ribose phosphate, but the pyrimidine ring is completed before it is attached. Also, deoxy conversion happens on free nucleotides, not on DNA already made.