Pathway · 3 proteins
Deoxyribonucleotide supply
Reduction and thymidylate chemistry supply DNA precursors.
How it works
- Ribonucleoside-diphosphate reductase, with an alpha and a beta subunit in VF5, reduces nucleoside diphosphates to deoxynucleoside diphosphates. This is the committed step for DNA precursors; the reducing electrons arrive through a partner system outside this module.
- dUTP diphosphatase hydrolyses dUTP to dUMP, which both limits uracil incorporation into DNA and supplies the substrate for thymidylate formation.
- A FAD-dependent thymidylate synthase (ThyX-type) methylates dUMP to dTMP using methylene-tetrahydrofolate. This is a flavin-dependent variant of the reaction, not the classical ThyA mechanism, and it ties DNA precursor supply to the folate pools in the cofactor system.
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 |
|---|---|---|---|---|---|
| Ribonucleoside-diphosphate reductase subunit alpha | 1.17.4.1 | a 2'-deoxyribonucleoside 5'-diphosphate + [thioredoxin]-disulfide + H2O = a ribonucleoside 5'-diphosphate + [thioredoxin]-dithiol | — | 801 | Step named |
| Ribonucleoside-diphosphate reductase subunit beta | 1.17.4.1 | a 2'-deoxyribonucleoside 5'-diphosphate + [thioredoxin]-disulfide + H2O = a ribonucleoside 5'-diphosphate + [thioredoxin]-dithiol | Fe cation | 696 | Step named |
| Deoxyuridine 5'-triphosphate nucleotidohydrolase | 3.6.1.23 | dUTP + H2O = dUMP + diphosphate + H(+) | Mg(2+) | 150 | Step named |
Also part of this pathway
These proteins are described under another pathway, but also take part here.
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| Flavin-dependent thymidylate synthaseHome: Not yet placed in a pathway | 2.1.1.148 | dUMP + (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + NADPH + H(+) = dTMP + (6S)-5,6,7,8-tetrahydrofolate + NADP(+) | — | 317 | Step named |
Origins
Where would the letters of DNA have come from before ribonucleotide reductase?
Cells make DNA letters from RNA letters: ribonucleotide reductase removes an oxygen from the sugar, and thymidylate synthase adds a methyl group to make thymine. Some authors take this as a sign that RNA came before DNA.
Direct prebiotic formation of deoxyribose, from acetaldehyde and glyceraldehyde phosphate, is considered theoretically possible but highly unlikely.
Removing that oxygen is hard chemistry: ribonucleotide reductase does it with a radical held on the protein itself, and the minimal set needs three proteins for this supply.
DNA is also not stable on its own: in a mammalian cell as many as 10,000 purines are lost from DNA every day, so DNA as a store of information needs repair from the start.
From the books: Atkins, Gesteland & Cech (eds.), RNA Worlds, p. 6; Ribas de Pouplana (ed.), The Genetic Code and the Origin of Life, p. 146; Nelson & Cox, Lehninger Principles of Biochemistry, p. 290.
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 · Pyrimidine biosynthesis · Interconversion and salvage · Aromatic amino acids · Purine metabolism · Pyrimidine metabolism · Histidine metabolism · Not yet placed in a pathway