NAD de novo biosynthesis I (from aspartate)

MetaCyc:PYRIDNUCSYN-PWY

NAD de novo biosynthesis I oxidizes L-aspartate to iminosuccinate, condenses iminosuccinate with dihydroxyacetone phosphate to form quinolinate, converts quinolinate through nicotinate beta-D-ribonucleotide to deamido-NAD(+), and amidates deamido-NAD(+) through either an ammonia-dependent or glutamine-dependent NAD(+) synthase.

Pathway type

cofactor biosynthesis

Organism scope

Bacteria NCBITaxon:2

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Pathway network

32 nodes · 48 asserted directed edges

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Reaction / activity
Chemical / cofactor
Other participant
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Bacteria `NCBITaxon:2`	taxon
L-aspartate oxidase `EC:1.4.3.16`	molecular activity
quinolinate synthase `EC:2.5.1.72`	molecular activity
quinolinate phosphoribosyltransferase `EC:2.4.2.19`	molecular activity
nicotinate-nucleotide adenylyltransferase `EC:2.7.7.18`	molecular activity
NAD(+) synthase `EC:6.3.1.5`	molecular activity
NAD(+) synthase (glutamine-hydrolyzing) `EC:6.3.5.1`	molecular activity
L-aspartate `CHEBI:29991`	small molecule
O2 `CHEBI:15379`	small molecule
iminosuccinate `CHEBI:77875`	small molecule
H2O2 `CHEBI:16240`	small molecule
dihydroxyacetone phosphate `CHEBI:57642`	small molecule
quinolinate `CHEBI:29959`	small molecule
phosphate `CHEBI:43474`	small molecule
H2O `CHEBI:15377`	small molecule
H(+) `CHEBI:15378`	small molecule
5-phospho-alpha-D-ribose 1-diphosphate `CHEBI:58017`	small molecule
nicotinate beta-D-ribonucleotide `CHEBI:57502`	small molecule
CO2 `CHEBI:16526`	small molecule
diphosphate `CHEBI:33019`	small molecule
ATP `CHEBI:30616`	small molecule
deamido-NAD(+) `CHEBI:58437`	small molecule
NH4(+) `CHEBI:28938`	small molecule
AMP `CHEBI:456215`	small molecule
NAD(+) `CHEBI:57540`	small molecule
L-glutamine `CHEBI:58359`	small molecule
L-glutamate `CHEBI:29985`	small molecule
L-aspartate oxidase reaction `RHEA:25877`	reaction	left to right
quinolinate synthase reaction `RHEA:25889`	reaction	left to right
quinolinate phosphoribosyltransferase reaction `RHEA:12735`	reaction	right to left
nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	reaction	left to right
ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	reaction	left to right
glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
O2 `CHEBI:15379`	consumes	L-aspartate oxidase reaction `RHEA:25877`	RHEA:25877 Source assertion: Rhea lists CHEBI:15379 on the substrates side of RHEA:25877 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25877']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-aspartate `CHEBI:29991`	consumes	L-aspartate oxidase reaction `RHEA:25877`	RHEA:25877 Source assertion: Rhea lists CHEBI:29991 on the substrates side of RHEA:25877 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25877']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-aspartate oxidase reaction `RHEA:25877`	produces	H2O2 `CHEBI:16240`	RHEA:25877 Source assertion: Rhea lists CHEBI:16240 on the products side of RHEA:25877 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25877']/rh:products; rh:contains/rh:compound/rh:accession`
L-aspartate oxidase reaction `RHEA:25877`	produces	iminosuccinate `CHEBI:77875`	RHEA:25877 Source assertion: Rhea lists CHEBI:77875 on the products side of RHEA:25877 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25877']/rh:products; rh:contains/rh:compound/rh:accession`
dihydroxyacetone phosphate `CHEBI:57642`	consumes	quinolinate synthase reaction `RHEA:25889`	RHEA:25889 Source assertion: Rhea lists CHEBI:57642 on the substrates side of RHEA:25889 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25889']/rh:substrates; rh:contains/rh:compound/rh:accession`
iminosuccinate `CHEBI:77875`	consumes	quinolinate synthase reaction `RHEA:25889`	RHEA:25889 Source assertion: Rhea lists CHEBI:77875 on the substrates side of RHEA:25889 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25889']/rh:substrates; rh:contains/rh:compound/rh:accession`
quinolinate synthase reaction `RHEA:25889`	produces	H2O `CHEBI:15377`	RHEA:25889 Source assertion: Rhea lists CHEBI:15377 on the products side of RHEA:25889 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25889']/rh:products; rh:contains/rh:compound/rh:accession`
quinolinate synthase reaction `RHEA:25889`	produces	H(+) `CHEBI:15378`	RHEA:25889 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:25889 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25889']/rh:products; rh:contains/rh:compound/rh:accession`
quinolinate synthase reaction `RHEA:25889`	produces	quinolinate `CHEBI:29959`	RHEA:25889 Source assertion: Rhea lists CHEBI:29959 on the products side of RHEA:25889 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25889']/rh:products; rh:contains/rh:compound/rh:accession`
quinolinate synthase reaction `RHEA:25889`	produces	phosphate `CHEBI:43474`	RHEA:25889 Source assertion: Rhea lists CHEBI:43474 on the products side of RHEA:25889 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/25889']/rh:products; rh:contains/rh:compound/rh:accession`
H(+) `CHEBI:15378`	consumes	quinolinate phosphoribosyltransferase reaction `RHEA:12735`	RHEA:12735 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:12735 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/12735']/rh:substrates; rh:contains/rh:compound/rh:accession`
quinolinate `CHEBI:29959`	consumes	quinolinate phosphoribosyltransferase reaction `RHEA:12735`	RHEA:12735 Source assertion: Rhea lists CHEBI:29959 on the substrates side of RHEA:12735 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/12735']/rh:substrates; rh:contains/rh:compound/rh:accession`
5-phospho-alpha-D-ribose 1-diphosphate `CHEBI:58017`	consumes	quinolinate phosphoribosyltransferase reaction `RHEA:12735`	RHEA:12735 Source assertion: Rhea lists CHEBI:58017 on the substrates side of RHEA:12735 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/12735']/rh:substrates; rh:contains/rh:compound/rh:accession`
quinolinate phosphoribosyltransferase reaction `RHEA:12735`	produces	CO2 `CHEBI:16526`	RHEA:12735 Source assertion: Rhea lists CHEBI:16526 on the products side of RHEA:12735 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/12735']/rh:products; rh:contains/rh:compound/rh:accession`
quinolinate phosphoribosyltransferase reaction `RHEA:12735`	produces	diphosphate `CHEBI:33019`	RHEA:12735 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:12735 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/12735']/rh:products; rh:contains/rh:compound/rh:accession`
quinolinate phosphoribosyltransferase reaction `RHEA:12735`	produces	nicotinate beta-D-ribonucleotide `CHEBI:57502`	RHEA:12735 Source assertion: Rhea lists CHEBI:57502 on the products side of RHEA:12735 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/12735']/rh:products; rh:contains/rh:compound/rh:accession`
H(+) `CHEBI:15378`	consumes	nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	RHEA:22861 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:22861 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22861']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	RHEA:22861 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:22861 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22861']/rh:substrates; rh:contains/rh:compound/rh:accession`
nicotinate beta-D-ribonucleotide `CHEBI:57502`	consumes	nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	RHEA:22861 Source assertion: Rhea lists CHEBI:57502 on the substrates side of RHEA:22861 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22861']/rh:substrates; rh:contains/rh:compound/rh:accession`
nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	produces	diphosphate `CHEBI:33019`	RHEA:22861 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:22861 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22861']/rh:products; rh:contains/rh:compound/rh:accession`
nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	produces	deamido-NAD(+) `CHEBI:58437`	RHEA:22861 Source assertion: Rhea lists CHEBI:58437 on the products side of RHEA:22861 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22861']/rh:products; rh:contains/rh:compound/rh:accession`
NH4(+) `CHEBI:28938`	consumes	ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	RHEA:21189 Source assertion: Rhea lists CHEBI:28938 on the substrates side of RHEA:21189 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21189']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	RHEA:21189 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:21189 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21189']/rh:substrates; rh:contains/rh:compound/rh:accession`
deamido-NAD(+) `CHEBI:58437`	consumes	ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	RHEA:21189 Source assertion: Rhea lists CHEBI:58437 on the substrates side of RHEA:21189 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21189']/rh:substrates; rh:contains/rh:compound/rh:accession`
ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	produces	H(+) `CHEBI:15378`	RHEA:21189 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:21189 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21189']/rh:products; rh:contains/rh:compound/rh:accession`
ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	produces	diphosphate `CHEBI:33019`	RHEA:21189 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:21189 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21189']/rh:products; rh:contains/rh:compound/rh:accession`
ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	produces	AMP `CHEBI:456215`	RHEA:21189 Source assertion: Rhea lists CHEBI:456215 on the products side of RHEA:21189 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21189']/rh:products; rh:contains/rh:compound/rh:accession`
ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	produces	NAD(+) `CHEBI:57540`	RHEA:21189 Source assertion: Rhea lists CHEBI:57540 on the products side of RHEA:21189 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/21189']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	RHEA:24385 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	RHEA:24385 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-glutamine `CHEBI:58359`	consumes	glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	RHEA:24385 Source assertion: Rhea lists CHEBI:58359 on the substrates side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:substrates; rh:contains/rh:compound/rh:accession`
deamido-NAD(+) `CHEBI:58437`	consumes	glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	RHEA:24385 Source assertion: Rhea lists CHEBI:58437 on the substrates side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:substrates; rh:contains/rh:compound/rh:accession`
glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	produces	H(+) `CHEBI:15378`	RHEA:24385 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:products; rh:contains/rh:compound/rh:accession`
glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	produces	L-glutamate `CHEBI:29985`	RHEA:24385 Source assertion: Rhea lists CHEBI:29985 on the products side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:products; rh:contains/rh:compound/rh:accession`
glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	produces	diphosphate `CHEBI:33019`	RHEA:24385 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:products; rh:contains/rh:compound/rh:accession`
glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	produces	AMP `CHEBI:456215`	RHEA:24385 Source assertion: Rhea lists CHEBI:456215 on the products side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:products; rh:contains/rh:compound/rh:accession`
glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	produces	NAD(+) `CHEBI:57540`	RHEA:24385 Source assertion: Rhea lists CHEBI:57540 on the products side of RHEA:24385 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24385']/rh:products; rh:contains/rh:compound/rh:accession`
L-aspartate oxidase `EC:1.4.3.16`	catalyzes	L-aspartate oxidase reaction `RHEA:25877`	RHEA:25876 Source assertion: Rhea associates EC:1.4.3.16 with the reaction family containing RHEA:25877. Source location `rh:ec`
quinolinate synthase `EC:2.5.1.72`	catalyzes	quinolinate synthase reaction `RHEA:25889`	RHEA:25888 Source assertion: Rhea associates EC:2.5.1.72 with the reaction family containing RHEA:25889. Source location `rh:ec`
quinolinate phosphoribosyltransferase `EC:2.4.2.19`	catalyzes	quinolinate phosphoribosyltransferase reaction `RHEA:12735`	RHEA:12733 Source assertion: Rhea associates EC:2.4.2.19 with the reaction family containing RHEA:12735. Source location `rh:ec`
nicotinate-nucleotide adenylyltransferase `EC:2.7.7.18`	catalyzes	nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	RHEA:22860 Source assertion: Rhea associates EC:2.7.7.18 with the reaction family containing RHEA:22861. Source location `rh:ec`
NAD(+) synthase `EC:6.3.1.5`	catalyzes	ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	RHEA:21188 Source assertion: Rhea associates EC:6.3.1.5 with the reaction family containing RHEA:21189. Source location `rh:ec`
NAD(+) synthase (glutamine-hydrolyzing) `EC:6.3.5.1`	catalyzes	glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	RHEA:24384 Source assertion: Rhea associates EC:6.3.5.1 with the reaction family containing RHEA:24385. Source location `rh:ec`
quinolinate phosphoribosyltransferase reaction `RHEA:12735`	precedes	nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	MetaCyc:PYRIDNUCSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:12735 before RHEA:22861 in this pathway. Shared intermediate: CHEBI:57502. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	precedes	ammonia-dependent NAD(+) synthase reaction `RHEA:21189`	MetaCyc:PYRIDNUCSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:22861 before RHEA:21189 in this pathway. Shared intermediate: CHEBI:58437. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
nicotinate-nucleotide adenylyltransferase reaction `RHEA:22861`	precedes	glutamine-dependent NAD(+) synthase reaction `RHEA:24385`	MetaCyc:PYRIDNUCSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:22861 before RHEA:24385 in this pathway. Shared intermediate: CHEBI:58437. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
L-aspartate oxidase reaction `RHEA:25877`	precedes	quinolinate synthase reaction `RHEA:25889`	MetaCyc:PYRIDNUCSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:25877 before RHEA:25889 in this pathway. Shared intermediate: CHEBI:77875. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
quinolinate synthase reaction `RHEA:25889`	precedes	quinolinate phosphoribosyltransferase reaction `RHEA:12735`	MetaCyc:PYRIDNUCSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:25889 before RHEA:12735 in this pathway. Shared intermediate: CHEBI:29959. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`

References

MetaCyc:PYRIDNUCSYN-PWY MetaCyc NAD de novo biosynthesis I pathway (source version: 22.5)
RHEA:25876 Rhea L-aspartate oxidase reaction (source version: 139)
RHEA:25877 Rhea iminosuccinate-forming direction (source version: 139)
RHEA:25888 Rhea quinolinate synthase reaction (source version: 139)
RHEA:25889 Rhea quinolinate-forming direction (source version: 139)
RHEA:12733 Rhea quinolinate phosphoribosyltransferase reaction (source version: 139)
RHEA:12735 Rhea nicotinate beta-D-ribonucleotide-forming direction (source version: 139)
RHEA:22860 Rhea nicotinate-nucleotide adenylyltransferase reaction (source version: 139)
RHEA:22861 Rhea deamido-NAD-forming direction (source version: 139)
RHEA:21188 Rhea ammonia-dependent NAD synthase reaction (source version: 139)
RHEA:21189 Rhea NAD-forming ammonia-dependent direction (source version: 139)
RHEA:24384 Rhea glutamine-dependent NAD synthase reaction (source version: 139)
RHEA:24385 Rhea NAD-forming glutamine-dependent direction (source version: 139)

Curation history

2026-10-05T06:25:52Z codex
- EDIT — Review causal chemistry and add sourced molecular context
  Reviewed the entire record against MetaCyc 22.5 native pathway XML (including nested pathways), Rhea 139 explicit sides and directions, ENZYME 02-Sep-2026, PubMed records, and reviewed UniProt 2026_03 annotations within the record's taxon scope. Replaced generated structured-source quotations with source_assertion and source_locator. Typed molecular activities and participants. Reaction count 6 to 6; 0 directed-ID corrections; 0 protein annotations, 0 cofactor annotations and 0 sourced locations. All Rhea reaction substrate/product sets checked against independent Rhea authority; native pathway leaf coverage and source exceptions recorded in reports/causal_graph_review/metacyc-review.json. Full source URLs, versions and byte hashes are in metacyc-sources.json. All 50 MetaCyc records passed native schema validation; six targeted chemistry/evidence regression tests passed. Missing protein or cofactor annotations are not treated as biological absence; qualifications and exclusions are preserved in the ledger.
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