Question

Commissioned Review Brief

Review Topic

De novo inosine monophosphate biosynthesis

Working Scope

A reusable pathway that assembles the purine ring on 5-phosphoribosyl diphosphate (PRPP) to form inosine monophosphate (IMP). The module represents ten ordered reaction positions and separates reaction roles from lineage-specific protein fusions. It includes alternative folate-dependent PurN and ATP/formate-dependent PurT routes for GAR formylation, and alternative two-enzyme and direct routes for AIR carboxylation. IMP-to-AMP and IMP-to-GMP branches are outside the module, although PurB also has a second physiological role in AMP synthesis.

Provisional Biological Outline

De novo inosine monophosphate biosynthesis
1. committed phosphoribosylamine formation
Amidophosphoribosyltransferase
- Glutamine PRPP amidotransferase (molecular player: PurF amidophosphoribosyltransferases; activity or role: amidophosphoribosyltransferase activity)
1. glycinamide ribonucleotide formation
Phosphoribosylamine--glycine ligase
- GAR synthetase (molecular player: PurD phosphoribosylamine--glycine ligases; activity or role: phosphoribosylamine-glycine ligase activity)
1. GAR formylation
Alternative GAR transformylation routes
- Alternative versions by one-carbon donor and energy coupling: GAR one-carbon donor route
- Folate-dependent PurN route
  - Folate-dependent GAR transformylase (molecular player: PurN GAR transformylases; activity or role: phosphoribosylglycinamide formyltransferase activity)
- ATP/formate-dependent PurT route
  - Formate-dependent GAR transformylase (molecular player: PurT formate-dependent GAR transformylases; activity or role: phosphoribosylglycinamide formyltransferase 2 activity)
1. formylglycinamidine ribonucleotide formation
Phosphoribosylformylglycinamidine synthase
- FGAM synthase (molecular player: large-type PurL FGAM synthases; activity or role: phosphoribosylformylglycinamidine synthase activity)
1. aminoimidazole ribonucleotide formation
Phosphoribosylformylglycinamidine cyclo-ligase
- AIR synthetase (molecular player: PurM AIR synthetases; activity or role: phosphoribosylformylglycinamidine cyclo-ligase activity)
1. aminoimidazole ribonucleotide carboxylation
Alternative AIR carboxylation routes
- Alternative versions by direct versus N5-CAIR intermediate: AIR-to-CAIR implementation
- Two-enzyme PurK/PurE route
  - 1. N5-CAIR formation
  - N5-CAIR synthetase
  - ATP-dependent N5-CAIR synthetase (molecular player: PurK N5-CAIR synthetases; activity or role: 5-(carboxyamino)imidazole ribonucleotide synthase activity)
  - 1. CAIR rearrangement
  - N5-CAIR mutase
  - N5-CAIR mutase (molecular player: PurE N5-CAIR mutases; activity or role: 5-(carboxyamino)imidazole ribonucleotide mutase activity)
- Direct AIR carboxylase route
  - Direct AIR carboxylase (molecular player: direct AIR carboxylases and PAICS-type fusion proteins; activity or role: phosphoribosylaminoimidazole carboxylase activity)
1. succinylaminoimidazole carboxamide ribonucleotide formation
SAICAR synthetase
- SAICAR synthetase (molecular player: PurC and PAICS SAICAR synthetases; activity or role: phosphoribosylaminoimidazolesuccinocarboxamide synthase activity)
1. aminoimidazole carboxamide ribonucleotide formation
SAICAR lyase
- SAICAR lyase (molecular player: PurB adenylosuccinate lyases; activity or role: SAICAR lyase activity)
1. formylaminoimidazole carboxamide ribonucleotide formation
AICAR transformylase
- AICAR transformylase (molecular player: PurH and ATIC AICAR transformylases; activity or role: phosphoribosylaminoimidazolecarboxamide formyltransferase activity)
1. inosine monophosphate formation
IMP cyclohydrolase
- IMP cyclohydrolase (molecular player: PurH and ATIC IMP cyclohydrolases; activity or role: IMP cyclohydrolase activity)

Known Relationships Among Steps

Amidophosphoribosyltransferase feeds into Phosphoribosylamine--glycine ligase: PurF supplies phosphoribosylamine to PurD.
Phosphoribosylamine--glycine ligase feeds into Alternative GAR transformylation routes: PurD supplies GAR to either transformylase route.
Alternative GAR transformylation routes feeds into Phosphoribosylformylglycinamidine synthase: GAR formylation supplies FGAR to PurL.
Phosphoribosylformylglycinamidine synthase feeds into Phosphoribosylformylglycinamidine cyclo-ligase: PurL supplies FGAM to PurM.
Phosphoribosylformylglycinamidine cyclo-ligase feeds into Alternative AIR carboxylation routes: PurM supplies AIR to the selected carboxylation route.
Alternative AIR carboxylation routes feeds into SAICAR synthetase: AIR carboxylation supplies CAIR to SAICAR synthetase.
SAICAR synthetase feeds into SAICAR lyase: PurC supplies SAICAR to PurB.
SAICAR lyase feeds into AICAR transformylase: PurB supplies AICAR to the penultimate reaction.
AICAR transformylase feeds into IMP cyclohydrolase: AICAR transformylation supplies FAICAR for ring closure.
N5-CAIR synthetase feeds into N5-CAIR mutase: PurK supplies N5-CAIR to PurE.

Assignment

Write a rigorous, review-style synthesis suitable for a molecular biology
audience. Treat the topic as a biological system whose boundaries, core
mechanisms, variants, and unresolved points should be made clear to readers who
know the field but are not specialists in this specific process.

The review should be explanatory rather than encyclopedic. Anchor broad claims
in primary literature or authoritative reviews, but keep the focus on how the
system works and how its parts fit together.

Questions To Address

Scope and boundaries
What exactly is included in this biological system?
Which neighboring pathways, organelle processes, complexes, or regulatory
events are often confused with it but should be treated separately?
Are there competing definitions in the literature?
Core mechanism
What is the best current model for the sequence of events?
Which steps are obligatory, which are conditional, and which are accessory?
What molecular assemblies, enzymes, receptors, adaptors, transporters, or
structural units carry out each major step?
Variation
How does the system vary across major evolutionary lineages?
Are there well-supported differences between cell types, tissues,
developmental stages, physiological states, or compartments?
Where are there alternative routes that achieve a similar outcome by
different molecular means?
Conservation and origin
What is the deepest plausible evolutionary origin of the system?
Which parts appear ancient and conserved, and which appear to be later
elaborations, replacements, or lineage-specific losses?
When a protein family has expanded, which family members are the best
representatives for understanding the ancestral role?
Physical and biological constraints
What steps must occur in a particular order?
Which events are mutually exclusive, compartment-specific, cell-type
specific, substrate-specific, or stage-specific?
What evidence rules out otherwise plausible paths through the system?
Evidence and controversy
Which mechanistic claims are strongly supported by experiments?
Where does the literature disagree, rely on indirect evidence, or mix data
from organisms that may not be comparable?
What are the most important open questions?

Output Format

Use the style and structure of a concise review article:

Executive summary
Definition and biological boundaries
Mechanistic overview
Major molecular players and active assemblies
Evolutionary and cell-biological variation
Constraints, dependencies, and failure modes
Controversies and open questions
Key references

Include citations for major claims, preferably PMIDs or DOIs. Be explicit about
uncertainty and avoid overgeneralizing from one organism, cell type, or assay
system to all biology.

Output

De novo Inosine Monophosphate Biosynthesis: A Conserved Ten-Reaction Module with Lineage-Specific Implementations

Review-style synthesis. Search date: 2026-07-25. Citations are given as PubMed IDs (PMID).

1. Executive summary

De novo inosine monophosphate (IMP) biosynthesis is the pathway that builds the purine ring atom-by-atom on 5-phosphoribosyl-1-diphosphate (PRPP), converting a sugar-phosphate and small metabolites (glutamine, glycine, one-carbon units, aspartate, CO₂/bicarbonate, ATP) into IMP, the first complete purine nucleotide and the common precursor of AMP and GMP. The system is best understood not as ten proteins but as ten ordered reaction roles that are conserved across all three domains of life, implemented by a variable set of proteins whose fusion state, cofactor choice and quaternary organization differ by lineage (PMID: 25230797; PMID: 33179964).

Three features organize this review. First, the reaction skeleton is deeply conserved and ancient, plausibly present in the last common ancestor, whereas the protein implementation is plastic: bacteria typically use single-function Pur enzymes, while humans compress the ten reactions into six polypeptides via gene fusions (trifunctional GART; bifunctional PAICS and ATIC) (PMID: 2050105; PMID: 35331738; PMID: 11323713). Second, two reaction positions have genuine alternative routes: step 3 (GAR formylation) can use a folate-dependent transformylase (PurN) or an ATP/formate-dependent transformylase (PurT) acting through a formyl-phosphate intermediate (PMID: 8501063; PMID: 9184151); step 6 (AIR carboxylation) can proceed by a two-enzyme bacterial route (PurK makes N⁵-CAIR, PurE mutase rearranges it to CAIR) or by a direct eukaryotic PurE-class carboxylase that fixes CO₂ onto AIR without an N⁵-CAIR intermediate (PMID: 10574791). Third, in eukaryotes the enzymes reversibly assemble into a channeling metabolon, the purinosome, coupling the reaction positions into high-flux, spatially organized synthesis (PMID: 18388293; PMID: 32299949) — a claim that has been both strongly supported and contested (PMID: 24413256).

The module's boundaries exclude the salvage pathway, PRPP synthesis, folate one-carbon metabolism, and the IMP→AMP and IMP→GMP branches — although one enzyme, PurB/adenylosuccinate lyase, is physiologically shared between the IMP module (step 8) and the IMP→AMP branch, a dual role with direct clinical consequences (PMID: 41053929; PMID: 35133277).

2. Definition and biological boundaries

2.1 What is included

The system comprises the reactions that assemble the purine ring on PRPP up to and including formation of IMP. In the canonical numbering used here:

Committed step — phosphoribosylamine (PRA) formation. Glutamine PRPP amidotransferase (PurF / PPAT / GPATase) transfers the glutamine amide nitrogen to PRPP, displacing pyrophosphate to give 5-phospho-β-D-ribosylamine (PMID: 9514258).
GAR formation. GAR synthetase (PurD) ligates glycine to PRA to form glycinamide ribonucleotide (GAR).
GAR formylation. A GAR transformylase adds a one-carbon (formyl) group to give formyl-GAR (FGAR) — alternative routes PurN vs PurT (PMID: 8501063).
FGAM formation. FGAM synthase (PurL) uses glutamine + ATP to convert FGAR to formylglycinamidine ribonucleotide (FGAM), with ammonia channeling (PMID: 18597481).
AIR formation. AIR synthetase (PurM), an ATP-dependent cyclo-ligase, closes the five-membered imidazole ring to give 5-aminoimidazole ribonucleotide (AIR) (PMID: 3015935).
AIR carboxylation. Carboxylation to 4-carboxy-AIR (CAIR) — alternative routes: PurK+PurE (via N⁵-CAIR) vs direct PurE-class carboxylase (PMID: 10574791).
SAICAR formation. SAICAR synthetase (PurC / PAICS) condenses aspartate onto CAIR to give SAICAR.
AICAR formation. SAICAR lyase (PurB / adenylosuccinate lyase) eliminates fumarate to give AICAR.
FAICAR formation. AICAR transformylase (PurH / ATIC) adds a second one-carbon unit to give formyl-AICAR (FAICAR).
IMP formation. IMP cyclohydrolase (PurH / ATIC) closes the second (pyrimidine) ring to yield IMP (PMID: 11323713).

2.2 What should be treated separately (neighbouring processes commonly conflated)

PRPP synthesis (PRPP synthetase, PRS). PRPP is the substrate, not part of the ring-assembly module, and is shared with pyrimidine, histidine, tryptophan and NAD biosynthesis and with purine salvage. It is an upstream supply node, frequently co-regulated but mechanistically distinct.
Purine salvage (HGPRT, APRT, adenosine kinase). Salvage regenerates nucleotides from preformed bases/nucleosides and is the dominant source in many differentiated tissues; it is a parallel, independent route to the same end nucleotides and is often confused with de novo synthesis in flux discussions.
Folate one-carbon metabolism. 10-formyl-THF (supplied through the MTHFD1/serine-hydroxymethyltransferase network) is the one-carbon donor for the PurN and PurH transformylase steps. It is a cofactor-supply pathway, not part of the ring assembly, though physically linked to the metabolon via MTHFD1 (PMID: 35331738).
IMP→AMP and IMP→GMP branches. Adenylosuccinate synthetase (PurA) + adenylosuccinate lyase (PurB) make AMP; IMP dehydrogenase (IMPDH) + GMP synthase make GMP. These lie downstream of IMP and are outside the module. The one caveat is PurB/ADSL, which physiologically catalyses both step 8 of the IMP module and the S-AMP→AMP reaction of the AMP branch (PMID: 41053929).
The purinosome as an organelle. The metabolon is a reversible, membraneless assembly, not a bounded organelle; treating it as a fixed structure over-states current evidence (see §7).

2.3 Competing definitions

Literature differs on enzyme count ("six enzymes/10 steps" in eukaryotes because of fusions vs "≥10 gene products" in many bacteria) (PMID: 18388293), on whether the purinosome should be counted as part of the "pathway" definition, and on whether the module ends at IMP or is described together with the AMP/GMP branches as "de novo purine biosynthesis." This review treats PRPP→IMP as the module and the branches as adjacent.

3. Mechanistic overview

3.1 Best current model of the sequence of events

The pathway is a strictly ordered assembly line: each enzyme's product is the obligatory substrate of the next, and the purine ring is constructed in a defined atom order (N9→C4/C5→N7→C8→N3→C6→N1→C2). Ordering is enforced both by substrate specificity and by the chemical instability of several intermediates (notably phosphoribosylamine, which is labile at physiological pH, and N⁵-CAIR), which strongly favors direct hand-off (channeling) over free diffusion (PMID: 34547238). The energetic cost is high: multiple steps consume ATP (PurD, PurL, PurM, PurT, PurK), making the pathway responsive to energy and purine status.

3.2 Obligatory, conditional and accessory elements

Obligatory reaction positions: all ten reaction roles are obligatory to reach IMP; none can be skipped because each supplies the next substrate.
Conditional (alternative) implementations: step 3 (PurN vs PurT) and step 6 (PurK/PurE two-enzyme vs direct carboxylase) are the two positions where different molecular means achieve the same transformation. Which is used depends on the organism (and, for step 3, on folate status and formate availability).
Accessory / supply elements: PRPP synthetase, the folate one-carbon network (MTHFD1), and — in eukaryotes — the purinosome scaffold and its regulators are accessory to, but not part of, the core chemistry.

3.3 Molecular assemblies per step

Distinct fold families carry out mechanistically related chemistry. Glutamine amidotransferase chemistry (PurF, PurL) uses a glutaminase domain feeding ammonia through an intramolecular channel to a synthetase domain (PMID: 9514258; PMID: 18597481). ATP-grasp enzymes (PurT, PurK, and mechanistically PurD) activate carboxylate/formate substrates via acyl-phosphate intermediates (PMID: 9184151). PurM defines its own AIR-synthetase fold (PMID: 26515187). The two terminal activities are fused in PurH/ATIC but use two separate active sites ~50 Å apart, with no intramolecular tunnel between them (PMID: 11323713).

4. Major molecular players and active assemblies

Step	Reaction role	Bacterial protein(s)	Human protein (fusion)	Notable mechanism / assembly
1	Committed PRA formation	PurF	PPAT (monofunctional)	Glutamine amidotransferase; AMP feedback at PRPP site; metal-free vs Fe–S subfamilies (PMID: 9514258)
2	GAR formation	PurD	GART (trifunctional, domain 1)	ATP-dependent ligase
3	GAR formylation	PurN or PurT	GART (folate/PurN-type domain)	PurN = folate-dependent; PurT = ATP/formate via formyl-phosphate (PMID: 8501063; PMID: 9184151)
4	FGAM formation	large PurL or smPurL+PurQ+PurS	PFAS/FGAMS (large PurL)	Glutamine amidotransferase; ammonia channel; fused vs multiprotein (PMID: 18597481; PMID: 15301532)
5	AIR formation	PurM	GART (AIRS domain)	ATP-dependent cyclo-ligase; conserved dimer (PMID: 26515187)
6	AIR carboxylation	PurK + PurE (class I mutase) or direct PurE (class II)	PAICS (direct carboxylase)	Two-enzyme N⁵-CAIR route vs direct CO₂ fixation (PMID: 10574791)
7	SAICAR formation	PurC	PAICS (SAICAR synthetase)	ATP-dependent aspartate condensation
8	AICAR formation	PurB	ADSL (monofunctional)	β-elimination of fumarate; also acts in AMP branch (PMID: 41053929)
9	FAICAR formation	PurH	ATIC (transformylase domain)	Folate-dependent transformylase (PMID: 11323713)
10	IMP formation	PurH	ATIC (cyclohydrolase domain)	Ring closure; no tunnel to transformylase site (PMID: 11323713)

Active supramolecular assemblies. In Bacillus subtilis/archaea, step 4 is reconstituted from smPurL, the glutaminase PurQ and the scaffolding PurS in a 2:1:1 PurS:Q:L complex whose assembly is glutamine/ADP-dependent (PMID: 18597481; PMID: 15301532). In eukaryotes, the whole pathway reversibly condenses into the purinosome at the microtubule/mitochondria interface; the bifunctional PAICS is an interaction hub that contacts nearly all other pathway enzymes and MTHFD1 (PMID: 35331738; PMID: 33179964). Single-cell chemical imaging shows nine enzymes channel intermediates, raising flux and tuning the AMP/GMP ratio (PMID: 32299949).

5. Evolutionary and cell-biological variation

5.1 Across evolutionary lineages

Antiquity. Comparative genomics across 1,606 genomes places nucleotide metabolism, including purine biosynthesis, in the last common ancestor of Bacteria, Archaea and Eukarya (PMID: 25230797). The reaction skeleton is therefore the ancient, conserved unit.
Committed step split. The first enzyme (GPATase) exists as a metal-free subfamily (prototype E. coli) and a Fe–S-cluster-containing subfamily (B. subtilis); a common ancestor may have carried an Fe–S cluster (PMID: 9514258).
Step 3 donor choice. Folate-dependent PurN is widespread; formate/ATP-dependent PurT (ATP-grasp, PurK-like) is present in many bacteria and provides redundancy under folate limitation (PMID: 8501063; PMID: 7496533). Eukaryotes generally use only the PurN (folate) chemistry, embedded in GART.
Step 4 architecture. Large single-chain PurL occurs in most Gram-negative bacteria and eukaryotes; small PurL + PurQ + PurS occurs in Gram-positive bacteria and archaea (PMID: 18597481).
Step 6 route. Bacteria/fungi use PurK + PurE (N⁵-CAIR mutase, class I); higher eukaryotes use a direct PurE-class carboxylase (class II) and lack PurK; the mutase-to-carboxylase divergence is a documented lineage-associated transition (PMID: 10574791; PMID: 25230797).
Gene fusions. Humans compress the ten reactions into six polypeptides — trifunctional GART (steps 2,3,5; 21q22.1), bifunctional PAICS (steps 6,7), bifunctional ATIC (steps 9,10), plus monofunctional PPAT, PFAS and ADSL (PMID: 2050105; PMID: 35331738; PMID: 11323713). Bacterial single-function Pur enzymes are the best representatives of the ancestral, unfused reaction roles.

5.2 Across cell types, states and compartments

De novo synthesis is most active in proliferating cells (embryonic tissue, activated lymphocytes, tumors) where salvage cannot meet demand; many differentiated tissues rely more on salvage. Purinosome assembly is inducible by purine depletion or increased demand and has been observed in multiple human lines (HeLa, HepG2, Saos-2, HEK293, fibroblasts, keratinocytes) (PMID: 22180458), and is dynamically regulated with cell state (PMID: 18388293; PMID: 33179964). The pathway is a validated antimicrobial/antifungal and anticancer target: ATIC is essential for growth and virulence in Cryptococcus neoformans (PMID: 36063996), and human ATIC is inhibited by potent antifolates (PMID: 14966129).

6. Constraints, dependencies, and failure modes

Order is fixed by substrate specificity: each enzyme accepts only the prior product. There is no experimentally supported shortcut through the ten positions.
Intermediate instability (phosphoribosylamine; N⁵-CAIR) makes free-diffusion routing costly and selects for channeling — the mechanistic rationale for the purinosome and for the bacterial PurLQS and PurK/PurE couplings (PMID: 34547238).
Mutually exclusive route choices. At step 6, an organism using the direct class II carboxylase does not use PurK/N⁵-CAIR; at step 3, PurN and PurT are redundant but only the double mutant is auxotrophic, showing either alone suffices (PMID: 8501063).
Cofactor dependence. Steps 3 (PurN) and 9 require 10-formyl-THF; folate/one-carbon insufficiency throttles the pathway, linking it to MTHFD1 and B-vitamin status (PMID: 35331738).
Regulation is multi-tier. Bacterial pur genes are transcriptionally co-repressed (PurR regulon; conserved purF/purM operator regions) (PMID: 3015935; PMID: 8501063); the committed enzyme PurF is allosterically feedback-inhibited by end-product mononucleotides at the PRPP site (PMID: 9514258). In eukaryotes an additional tier is metabolon (dis)assembly (PMID: 33179964).
Failure modes with clinical readout. Loss of ADSL (step 8, also AMP branch) causes a neurometabolic disorder (>80 patients) with psychomotor retardation, epilepsy and autistic features; diagnostic accumulation of dephosphorylated SAICAr and S-Ado; patient fibroblasts show 1–4% residual activity and loss of purinosome assembly, with pathology attributed largely to SAICAr toxicity and secondarily to reduced purine supply and impaired ciliogenesis (PMID: 41053929; PMID: 25112391; PMID: 35133277). ATIC/ADSL mutations destabilize purinosome assembly in proportion to clinical severity (PMID: 22180458).

7. Controversies and open questions

Is the purinosome a functional channeling metabolon or an artifact of over-expression? The Benkovic group's live-cell imaging, metabolomics and GCIB-SIMS argue for a genuine, reversible, flux-enhancing metabolon that channels intermediates from PRPP to AMP/GMP (PMID: 18388293; PMID: 32299949; PMID: 33179964). A dissenting view held that fluorescently tagged "purinosome bodies" may correspond to protein aggregation/stress bodies rather than physiological channeling complexes (PMID: 24413256). More recent endogenous-level and single-cell data have shifted the balance toward a real metabolon, but the stoichiometry, condensate nature, and in vivo flux contribution remain incompletely resolved.
Nature of channeling without tunnels. PurH/ATIC has two active sites ~50 Å apart with no connecting tunnel (PMID: 11323713); how intermediates are retained here — by electrostatics, proximity within the metabolon, or transient diffusion — is unsettled.
Regulation of assembly. Candidate kinases and signaling inputs (extensive phosphorylation of pathway enzymes) are proposed to drive purinosome assembly/disassembly, but a definitive signaling circuit is not established (PMID: 33179964).
Organism transferability. Much mechanistic detail comes from E. coli, B. subtilis, Salmonella, Thermotoga and avian/human enzymes; route usage (PurN/PurT, PurK/PurE, large/small PurL) differs by lineage, so conclusions should not be generalized across organisms without checking gene complement.
Moonlighting/branch coupling. The physiological consequences of PurB/ADSL serving two pathways, and proposed non-canonical roles of pathway intermediates (e.g., SAICAR signaling), warrant further, organism-specific study.

Most important open questions: the precise composition and flux stoichiometry of the endogenous purinosome; the signaling logic that assembles it; and whether alternative-route enzymes (PurT, PurK/PurE vs class II) confer condition-specific fitness advantages beyond simple redundancy.

8. Key references

Armenta-Medina D, et al. Comparative genomics of nucleotide metabolism: a tour to the past of the three cellular domains of life. BMC Genomics 2014. PMID: 25230797.
Pareek V, Pedley AM, Benkovic SJ. Human de novo purine biosynthesis. Crit Rev Biochem Mol Biol 2021. PMID: 33179964.
An S, Kumar R, Sheets ED, Benkovic SJ. Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science 2008. PMID: 18388293.
Pareek V, et al. Metabolomics and mass spectrometry imaging reveal channeled de novo purine synthesis in cells. Science 2020. PMID: 32299949.
Pareek V, et al. Metabolic channeling: predictions, deductions, and evidence. Mol Cell 2021. PMID: 34547238.
Zhao H, et al. Revisiting and revising the purinosome. Mol Biosyst 2014. PMID: 24413256.
He J, et al. Multienzyme interactions of PAICS facilitate purinosome formation and metabolic channeling. BMC Biol 2022. PMID: 35331738.
Muchmore CRA, et al. Crystal structure of glutamine PRPP amidotransferase from E. coli. Protein Sci 1998. PMID: 9514258.
Nygaard P, Smith JM. Evidence for a novel GAR transformylase (PurT) in E. coli. J Bacteriol 1993. PMID: 8501063.
Marolewski AE, et al. Formyl phosphate: intermediate in the PurT GAR transformylase reaction. Biochemistry 1997. PMID: 9184151.
Saxild HH, et al. Functional analysis of B. subtilis purT. J Bacteriol 1995. PMID: 7496533.
Morar M, et al. FGAR amidotransferase (PurL) from Thermotoga maritima: complex formation. Biochemistry 2008. PMID: 18597481.
Anand R, et al. A model for the B. subtilis FGAR amidotransferase multiprotein complex. Biochemistry 2004. PMID: 15301532.
Smith JM, Daum HA. Nucleotide sequence of purM (AIR synthetase) of E. coli. J Biol Chem 1986. PMID: 3015935.
Kanagawa M, et al. Crystal structures of PurM from Thermus thermophilus and Geobacillus kaustophilus. Acta Crystallogr F 2016. PMID: 26515187.
Mathews II, et al. Crystal structure of E. coli PurE, an unusual mutase. Structure 1999. PMID: 10574791.
Greasley SE, et al. Crystal structure of the bifunctional transformylase/cyclohydrolase (ATIC). Nat Struct Biol 2001. PMID: 11323713.
Cheong CG, et al. Human ATIC in complex with sulfonyl antifolates. J Biol Chem 2004. PMID: 14966129.
Le Nours J, et al. Structural analyses of ATIC (PurH) from M. tuberculosis. 2011. PMID: 21956117.
Wizrah MSI, et al. ATIC is essential for de novo purine biosynthesis and infection by Cryptococcus neoformans. J Biol Chem 2022. PMID: 36063996.
Gnirke A, et al. Cloning and in vivo expression of the human GART gene. Genomics 1991. PMID: 2050105.
Rousselot-Pailley B, et al. Allopurinol treatment in adenylosuccinate lyase deficiency. 2025. PMID: 41053929.
Dutto I, et al. Pathway-specific effects of ADSL deficiency on neurodevelopment. 2022. PMID: 35133277.
Jurecka A, et al. Adenylosuccinate lyase deficiency. J Inherit Metab Dis 2015. PMID: 25112391.
Baresova V, et al. Mutations of ATIC and ADSL affect purinosome assembly. Hum Mol Genet 2012. PMID: 22180458.

Uncertainty statement. Structural and mechanistic claims are strongest for the individual enzymes (multiple crystal structures across bacteria, archaea and vertebrates). The channeling/purinosome model is well supported in cultured human cells but its endogenous stoichiometry and in vivo flux contribution remain partly inferential, and route usage varies by lineage; readers should not extrapolate a single organism's gene complement or a single cell line's behavior to all biology.

Artifacts

OpenScientist final report (not archived)
OpenScientist final report (not archived)

Citations

PMID:25230797
PMID:33179964
PMID:2050105
PMID:35331738
PMID:11323713
PMID:8501063
PMID:9184151
PMID:10574791
PMID:18388293
PMID:32299949
PMID:24413256
PMID:41053929
PMID:35133277
PMID:9514258
PMID:18597481
PMID:3015935
PMID:34547238
PMID:26515187
PMID:15301532
PMID:7496533
PMID:22180458
PMID:36063996
PMID:14966129
PMID:25112391
PMID:21956117