Pathway · 9 proteins
Pyrimidine biosynthesis
Carbamoyl-phosphate-derived chemistry supplies pyrimidine nucleotides.
How it works
- Carbamoyl phosphate is made by carbamoyl-phosphate synthase from the glutamine-hydrolysing large and small subunits listed here, then combined with aspartate by aspartate carbamoyltransferase to give carbamoyl aspartate.
- Dihydroorotase closes the ring to dihydroorotate, and a dihydroorotate dehydrogenase with its own electron-transfer subunit oxidises it to orotate at the membrane, passing electrons toward the quinone pool.
- Orotate phosphoribosyltransferase attaches orotate to PRPP, and orotidine-5'-phosphate decarboxylase releases CO2 to give UMP. UMP is the branch point for UTP, CTP and, after reduction, the deoxypyrimidines.
Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.
Its proteins
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| Putative dihydroorotate dehydrogenase A (fumarate) | 1.3.98.1 | (S)-dihydroorotate + fumarate = orotate + succinate | FMN | 306 | Step named |
| Carbamoyl phosphate synthase large chain, C-terminal section | 6.3.4.16; 6.3.5.5 | hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) | Mg(2+), Mn(2+) | 537 | Step named |
| Dihydroorotate dehydrogenase B (NAD(+)), electron transfer subunit homolog | — | — | [2Fe-2S] cluster | 251 | Step named |
| Orotidine 5'-phosphate decarboxylase | 4.1.1.23 | orotidine 5'-phosphate + H(+) = UMP + CO2 | — | 231 | Step named |
| Orotate phosphoribosyltransferase | 2.4.2.10 | orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate | 5-phospho-alpha-D-ribose 1-diphosphate, Mg(2+) | 183 | Step named |
| Carbamoyl phosphate synthase large chain, N-terminal section | 6.3.4.16; 6.3.5.5 | hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) | Mg(2+), Mn(2+) | 557 | Step named |
| Aspartate carbamoyltransferase catalytic subunit | 2.1.3.2 | carbamoyl phosphate + L-aspartate = N-carbamoyl-L-aspartate + phosphate + H(+) | — | 291 | Step named |
| Carbamoyl phosphate synthase small chain | 6.3.5.5 | hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+) | — | 371 | Step named |
| Dihydroorotase | 3.5.2.3 | (S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate + H(+) | Zn(2+) | 422 | Step named |
Origins
Could cytosine, uracil and their nucleotides have formed before this pathway existed?
Powner and colleagues (2009) made activated pyrimidine ribonucleotides under conditions they consider plausible for the early Earth. A later photochemical step turns one into uridine cleanly, because ultraviolet light destroys the side products while the cyclic nucleotide resists it.
That laboratory route does not follow the cell's. The cell makes UMP in six steps from carbamoyl phosphate and aspartate, closes the ring, and only then attaches it to PRPP. Nine proteins of the minimal set serve this route, and PRPP itself has no known prebiotic source.
The reported syntheses add their reagents in a chosen order under controlled conditions. That is chemistry guided by researchers, not yet a route an unattended early-Earth setting has been shown to follow.
From the books: Atkins, Gesteland & Cech (eds.), RNA Worlds, p. 6; Ruiz-Mirazo et al., Prebiotic Systems Chemistry, PDF p. 12; Zubay, Origins of Life on Earth and in the Cosmos, p. 232.
The wider question for this part of the cell: origins for making dna and rna letters.
Sources
- Atlas pathway grouping from the VF5 reference-genome system map (Deckert et al. 1998; Braakman & Smith 2014)
Other pathways in this group: Purine biosynthesis · Interconversion and salvage · Deoxyribonucleotide supply · Aromatic amino acids · Purine metabolism · Pyrimidine metabolism · Histidine metabolism · Not yet placed in a pathway