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HomeMetabolismNucleotide MetabolismPurine nucleotide synthesis
Pathway

Purine nucleotide synthesis

Homo sapiens · Cytosol · 13 reactions

De novo purine synthesis builds the purine ring atom by atom on activated ribose phosphate. The pathway makes IMP, which branches to AMP and GMP. Ring atoms come from glycine, glutamine, aspartate, carbon dioxide, and folate-bound one-carbon units.

REACTOME IDENTIFIERR-HSA-73817View source record ↗

Pathway scope

NETWORK MAP

The pathway branches at IMP and several ring-building reactions are grouped; no single overall stoichiometry is shown.

Overview

EXPLORE BY LEVEL

Purine nucleotide synthesis is a set of connected chemical steps in human cells. De novo purine synthesis builds the purine ring atom by atom on activated ribose phosphate. The makes IMP, which branches to AMP and GMP. Ring atoms come from glycine, glutamine, aspartate, , and folate-bound one-carbon units.

WHY THE FLOW CHANGES

Regulation

Compare fed and fasting

Purine end products provide feedback on new nucleotide synthesis.

Can slow downAMP, GMP, and IMP

Purine nucleotides feed back on early committed steps and help balance the nucleotide pool.

Can speed upPRPP availability

Phosphoribosyl pyrophosphate availability supports de novo purine synthesis.

Context mattersAMP/GMP branch demand

Separate branch-point feedback helps balance adenine and guanine nucleotide production.

How to read this map

This is an instructional map of selected reactions, not a complete inventory of every reaction in the body. Some steps are grouped; transport, alternate routes, tissue differences, or full molecule balances may be summarized. The Research notes explain this map’s specific limits.

Explore the reaction map and enzyme steps

Pathway map

GENERATED FROM STRUCTURED REACTIONS

Select a molecule or enzyme to inspect it. Select a step number to open its full reaction detail.

  1. Ribose activation

    Ribose 5-phosphate is activated to PRPP.

    1. Step 1Irreversible

  2. Purine-ring assembly

    Nitrogen, carbon, glycine, and one-carbon units are added through a sequence of reactions to form IMP.

    1. Step 2Irreversible
    2. Step 3Irreversible · ATP → ADP + Pi
    3. Step 4Irreversible
    4. Step 5Irreversible · ATP → ADP + Pi
    5. Step 6Irreversible · ATP → ADP + Pi
    6. Step 7Irreversible
    7. Step 8Irreversible · ATP → ADP + Pi
    8. Step 9Irreversible
    9. Step 10Irreversible
    10. Step 11Irreversible

  3. AMP and GMP branches

    IMP is converted separately to adenylate or guanylate nucleotides.

      AMP BRANCH
      1. Step 12Irreversible · GTP → GDP

      IMP is converted to AMP through adenylosuccinate; the map groups its two reactions.

      GMP BRANCH
      1. Step 13Irreversible · ATP → AMP + PPi

      IMP is oxidized to XMP and amidated to GMP; the map groups the two reactions.

    Reaction steps

    1PRPP formationRibose 5-phosphate + ATP → 5-Phosphoribosyl 1-pyrophosphate + Adenosine monophosphate + PyrophosphateIrreversible

    PRPP synthetase activates ribose 5-phosphate using ATP.

    REACTION · PER TURN + yields + +
    Enzyme
    EC 2.7.6.1 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Ribose activation
    MECHANISM & CONTEXT

    PRPP is a shared precursor for purine synthesis, pyrimidine synthesis, and salvage pathways.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    2Committed purine nitrogen addition5-Phosphoribosyl 1-pyrophosphate + Glutamine → 5-Phosphoribosylamine + Glutamate + PyrophosphateIrreversible

    Glutamine-PRPP amidotransferase commits PRPP to de novo purine synthesis.

    REACTION · PER TURN + yields + +
    Enzyme
    EC 2.4.2.14 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    This regulated step adds a glutamine-derived nitrogen to the ribose scaffold.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    3Glycine addition5-Phosphoribosylamine + Glycine → Glycinamide ribonucleotideIrreversible

    GAR synthetase adds glycine and uses ATP.

    REACTION · PER TURN + + yields + +
    Enzyme
    EC 6.3.4.13 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    Glycine contributes two carbon atoms and one nitrogen atom to the purine ring.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    4First one-carbon transferGlycinamide ribonucleotide + 10-Formyltetrahydrofolate → Formylglycinamide ribonucleotide + TetrahydrofolateIrreversible

    GAR transformylase transfers a formyl group from 10-formyl-THF.

    REACTION · PER TURN + yields +
    Enzyme
    EC 2.1.2.2 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    The folate-bound carbon becomes one of the purine-ring carbon atoms.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    5Glutamine-dependent nitrogen additionFormylglycinamide ribonucleotide + Glutamine → Formylglycinamidine ribonucleotide + GlutamateIrreversible

    FGAM synthetase supplies another ring nitrogen from glutamine.

    REACTION · PER TURN + + yields + + +
    Enzyme
    EC 6.3.5.3 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    This reaction helps establish the second ring nitrogen in the purine core.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    6Imidazole ring closureFormylglycinamidine ribonucleotide → 5-Aminoimidazole ribonucleotideIrreversible

    AIR synthetase closes the first purine ring.

    REACTION · PER TURN + yields + +
    Enzyme
    EC 6.3.3.1 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    The pathway forms the imidazole portion before adding the second ring.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    7AIR carboxylation5-Aminoimidazole ribonucleotide + Bicarbonate → Carboxyaminoimidazole ribonucleotideIrreversible

    AIR carboxylase adds carbon dioxide to form CAIR.

    REACTION · PER TURN + yields
    Enzyme
    EC 4.1.1.21 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    This reaction forms the carboxylated purine-ring intermediate before aspartate is added.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    8Aspartate additionCarboxyaminoimidazole ribonucleotide + Aspartate → Succinylaminoimidazole carboxamide ribonucleotideIrreversible

    SAICAR synthetase adds aspartate to CAIR using ATP.

    REACTION · PER TURN + + yields + +
    Enzyme
    EC 6.3.4.13 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    Adenylosuccinate lyase then removes fumarate, retaining aspartate-derived atoms in the purine ring.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    9Fumarate releaseSuccinylaminoimidazole carboxamide ribonucleotide → 5-Aminoimidazole-4-carboxamide ribonucleotide + FumarateIrreversible

    Adenylosuccinate lyase activity releases fumarate and forms AICAR.

    REACTION · PER TURNyields +
    Enzyme
    EC 4.3.2.2 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    Fumarate is the carbon skeleton left when aspartate contributes atoms to the purine ring.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    10Second one-carbon transfer5-Aminoimidazole-4-carboxamide ribonucleotide + 10-Formyltetrahydrofolate → Formamidoimidazole carboxamide ribonucleotide + TetrahydrofolateIrreversible

    A second folate-derived formyl group is added to the purine precursor.

    REACTION · PER TURN + yields +
    Enzyme
    EC 2.1.2.3 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    This supplies the final carbon atom needed for the purine ring.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    11IMP ring completionFormamidoimidazole carboxamide ribonucleotide → Inosine monophosphateIrreversible

    ATIC cyclizes FAICAR to produce inosine monophosphate.

    REACTION · PER TURNyields
    Enzyme
    EC 3.5.4.10 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    Purine-ring assembly
    MECHANISM & CONTEXT

    IMP is the first complete purine nucleotide and the branch point for AMP and GMP synthesis.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    12AMP branchInosine monophosphate + Aspartate → Adenosine monophosphate + FumarateIrreversible

    The AMP branch uses aspartate and GTP to make AMP and fumarate.

    REACTION · PER TURN + + yields + +
    Enzyme
    EC 6.3.4.4 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    AMP and GMP branches
    MECHANISM & CONTEXT

    Adenylosuccinate synthetase and adenylosuccinate lyase perform two reactions; the map groups the branch endpoint.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    13GMP branchInosine monophosphate + Glutamine → Guanosine monophosphate + GlutamateIrreversible

    The GMP branch oxidizes IMP to XMP and adds nitrogen from glutamine using ATP.

    REACTION · PER TURN + + yields + + +
    Enzyme
    EC 6.3.5.2 ↗
    Cofactors
    No metal cofactor listed.
    Reversibility
    Irreversible under cellular conditions. This is a control point.
    Runs per ribose 5-phosphate
    Once
    Stage
    AMP and GMP branches
    MECHANISM & CONTEXT

    IMP dehydrogenase and GMP synthetase catalyze the two grouped reactions.

    Evidence for this step: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    Research sources, claims, and curation

    Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)

    Reactome · Homo sapiens · Reviewed Reactome human pathway used for reaction sequence and context.

    Claims

    De novo purine synthesis builds the purine ring atom by atom on activated ribose phosphate. The pathway makes IMP, which branches to AMP and GMP. Ring atoms come from glycine, glutamine, aspartate, carbon dioxide, and folate-bound one-carbon units.

    Curation notes

    • Purine-ring assembly is summarized from the reviewed Reactome pathway; the step descriptions identify where several individual reactions are grouped.
    • AMP and GMP are alternative products of IMP and are displayed as parallel branches.
    • PRPP synthetase uses ATP to AMP and pyrophosphate; the associated phosphate bookkeeping is simplified.