Pathway · 10 proteins
Purine biosynthesis
A multistep route produces the purine ring and IMP.
How it works
- PRPP receives an amide nitrogen from glutamine (amidophosphoribosyltransferase), releasing pyrophosphate, and glycine is then added as a whole residue (phosphoribosylamine--glycine ligase). The purine ring is built on the ribose, not assembled separately and attached afterwards.
- Formylation (phosphoribosylglycinamide formyltransferase), formylglycinamidine synthesis by the PurS/PurL/PurQ subunits of FGAM synthase, and cyclisation close the imidazole ring to give AICAR. AICAR is then formylated to FAICAR and cyclised to IMP.
- IMP is the first complete purine nucleotide. Adenylosuccinate synthase and lyase lead toward AMP, while IMP dehydrogenase and GMP synthase (under interconversion) lead toward GMP. The annotated set matches the textbook route; it does not by itself show flux in VF5.
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 |
|---|---|---|---|---|---|
| Phosphoribosylformylglycinamidine synthase subunit PurQ | 3.5.1.2; 6.3.5.3 | N(2)-formyl-N(1)-(5-phospho-beta-D-ribosyl)glycinamide + L-glutamine + ATP + H2O = 2-formamido-N(1)-(5-O-phospho-beta-D-ribosyl)acetamidine + L-glutamate + ADP + phosphate + H(+) | — | 227 | Step named |
| Amidophosphoribosyltransferase | 2.4.2.14 | 5-phospho-beta-D-ribosylamine + L-glutamate + diphosphate = 5-phospho-alpha-D-ribose 1-diphosphate + L-glutamine + H2O | [4Fe-4S] cluster, Mg(2+) | 465 | Step named |
| Adenylosuccinate synthetase | 6.3.4.4 | IMP + L-aspartate + GTP = N(6)-(1,2-dicarboxyethyl)-AMP + GDP + phosphate + 2 H(+) | Mg(2+) | 432 | Step named |
| Phosphoribosylformylglycinamidine synthase subunit PurL | 6.3.5.3 | N(2)-formyl-N(1)-(5-phospho-beta-D-ribosyl)glycinamide + L-glutamine + ATP + H2O = 2-formamido-N(1)-(5-O-phospho-beta-D-ribosyl)acetamidine + L-glutamate + ADP + phosphate + H(+) | Mg(2+) | 745 | Step named |
| Bifunctional purine biosynthesis protein PurH | 2.1.2.3; 3.5.4.10 | (6R)-10-formyltetrahydrofolate + 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide + (6S)-5,6,7,8-tetrahydrofolate | — | 506 | Step named |
| Phosphoribosylaminoimidazole-succinocarboxamide synthase | 6.3.2.6 | 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate + ATP = (2S)-2-[5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamido]succinate + ADP + phosphate + 2 H(+) | — | 216 | Step named |
| Adenylosuccinate lyase | 4.3.2.2 | N(6)-(1,2-dicarboxyethyl)-AMP = fumarate + AMP | — | 437 | Step named |
| Phosphoribosylamine--glycine ligase | 6.3.4.13 | 5-phospho-beta-D-ribosylamine + glycine + ATP = N(1)-(5-phospho-beta-D-ribosyl)glycinamide + ADP + phosphate + H(+) | Mg(2+), Mn(2+) | 424 | Step named |
| Phosphoribosylformylglycinamidine cyclo-ligase | 6.3.3.1 | 2-formamido-N(1)-(5-O-phospho-beta-D-ribosyl)acetamidine + ATP = 5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + ADP + phosphate + H(+) | — | 331 | Step named |
| Phosphoribosylglycinamide formyltransferase | 2.1.2.2 | N(1)-(5-phospho-beta-D-ribosyl)glycinamide + (6R)-10-formyltetrahydrofolate = N(2)-formyl-N(1)-(5-phospho-beta-D-ribosyl)glycinamide + (6S)-5,6,7,8-tetrahydrofolate + H(+) | — | 216 | Step named |
Origins
Could adenine and guanine, and the nucleotides built from them, have formed before this ten-step pathway existed?
How it was discovered
- 1950sThe research groups of John Buchanan and Robert Greenberg work out the ten-step pathway to the first purine nucleotide; isolating its intermediates takes about ten years. The work starts from the way pigeons get rid of nitrogen as uric acid.Horton et al., Principles of Biochemistry, p. 629; Garrett & Grisham, Biochemistry, PDF p. 965
Hydrogen cyanide is the usual proposed starting point: four molecules condense to diaminomaleonitrile, which ultraviolet light converts into aminoimidazolecarbonitrile, the gateway to the purines. Zubay notes parallels between this route and the later steps of the cell's pathway.
Powner and colleagues found a high-yielding one-pot reaction that gives plausible purine precursors. Zubay notes, however, that conditions for forming nucleosides from a base and a sugar had been found only for hypoxanthine.
The cell does not build the base and then attach it to the sugar. It builds the purine ring on activated ribose (PRPP), atom by atom, using glutamine, glycine, aspartate, carbon dioxide and two folate-carried carbons, with ten proteins of the minimal set.
In many bacteria the end product switches the pathway off through an RNA riboswitch. The guanine-sensing switch turns off the genes for purine biosynthesis without any regulatory protein.
From the books: Zubay, Origins of Life on Earth and in the Cosmos, PDF p. 185 and p. 223; Ruiz-Mirazo et al., Prebiotic Systems Chemistry, PDF p. 12; Alberts et al., Molecular Biology of the Cell, p. 446.
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: Pyrimidine biosynthesis · Interconversion and salvage · Deoxyribonucleotide supply · Aromatic amino acids · Purine metabolism · Pyrimidine metabolism · Histidine metabolism · Not yet placed in a pathway