ppGpp metabolism

MetaCyc:PPGPPMET-PWY

ppGpp metabolism interconverts GDP, GTP, guanosine 3'-diphosphate 5'-triphosphate, and guanosine 3',5'-bis(diphosphate) through kinase, pyrophosphokinase, and hydrolase reactions.

Pathway type

metabolic regulator biosynthesis

Organism scope

Bacteria NCBITaxon:2

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Pathway network

21 nodes · 41 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
nucleoside-diphosphate kinase `EC:2.7.4.6`	molecular activity
GTP diphosphokinase `EC:2.7.6.5`	molecular activity
guanosine-3',5'-bis(diphosphate) 3'-diphosphatase `EC:3.1.7.2`	molecular activity
guanosine-5'-triphosphate,3'-diphosphate diphosphatase `EC:3.6.1.40`	molecular activity
GDP `CHEBI:58189`	small molecule
ATP `CHEBI:30616`	small molecule
GTP `CHEBI:37565`	small molecule
ADP `CHEBI:456216`	small molecule
guanosine 3'-diphosphate 5'-triphosphate `CHEBI:142410`	small molecule
H2O `CHEBI:15377`	small molecule
diphosphate `CHEBI:33019`	small molecule
H(+) `CHEBI:15378`	small molecule
guanosine 3',5'-bis(diphosphate) `CHEBI:77828`	small molecule
AMP `CHEBI:456215`	small molecule
phosphate `CHEBI:43474`	small molecule
GDP kinase reaction `RHEA:27687`	reaction	left to right
guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	reaction	left to right
GDP pyrophosphokinase reaction `RHEA:28099`	reaction	left to right
GTP pyrophosphokinase reaction `RHEA:22089`	reaction	left to right
ppGpp 3'-diphosphatase reaction `RHEA:14254`	reaction	left to right
pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
ATP `CHEBI:30616`	consumes	GDP kinase reaction `RHEA:27687`	RHEA:27687 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:27687 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27687']/rh:substrates; rh:contains/rh:compound/rh:accession`
GDP `CHEBI:58189`	consumes	GDP kinase reaction `RHEA:27687`	RHEA:27687 Source assertion: Rhea lists CHEBI:58189 on the substrates side of RHEA:27687 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27687']/rh:substrates; rh:contains/rh:compound/rh:accession`
GDP kinase reaction `RHEA:27687`	produces	GTP `CHEBI:37565`	RHEA:27687 Source assertion: Rhea lists CHEBI:37565 on the products side of RHEA:27687 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27687']/rh:products; rh:contains/rh:compound/rh:accession`
GDP kinase reaction `RHEA:27687`	produces	ADP `CHEBI:456216`	RHEA:27687 Source assertion: Rhea lists CHEBI:456216 on the products side of RHEA:27687 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/27687']/rh:products; rh:contains/rh:compound/rh:accession`
guanosine 3'-diphosphate 5'-triphosphate `CHEBI:142410`	consumes	guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	RHEA:33056 Source assertion: Rhea lists CHEBI:142410 on the substrates side of RHEA:33056 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33056']/rh:substrates; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	RHEA:33056 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:33056 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33056']/rh:substrates; rh:contains/rh:compound/rh:accession`
guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	produces	H(+) `CHEBI:15378`	RHEA:33056 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:33056 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33056']/rh:products; rh:contains/rh:compound/rh:accession`
guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	produces	diphosphate `CHEBI:33019`	RHEA:33056 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:33056 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33056']/rh:products; rh:contains/rh:compound/rh:accession`
guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	produces	GTP `CHEBI:37565`	RHEA:33056 Source assertion: Rhea lists CHEBI:37565 on the products side of RHEA:33056 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/33056']/rh:products; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	GDP pyrophosphokinase reaction `RHEA:28099`	RHEA:28099 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:28099 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28099']/rh:substrates; rh:contains/rh:compound/rh:accession`
GDP `CHEBI:58189`	consumes	GDP pyrophosphokinase reaction `RHEA:28099`	RHEA:28099 Source assertion: Rhea lists CHEBI:58189 on the substrates side of RHEA:28099 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28099']/rh:substrates; rh:contains/rh:compound/rh:accession`
GDP pyrophosphokinase reaction `RHEA:28099`	produces	AMP `CHEBI:456215`	RHEA:28099 Source assertion: Rhea lists CHEBI:456215 on the products side of RHEA:28099 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28099']/rh:products; rh:contains/rh:compound/rh:accession`
GDP pyrophosphokinase reaction `RHEA:28099`	produces	guanosine 3',5'-bis(diphosphate) `CHEBI:77828`	RHEA:28099 Source assertion: Rhea lists CHEBI:77828 on the products side of RHEA:28099 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/28099']/rh:products; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	GTP pyrophosphokinase reaction `RHEA:22089`	RHEA:22089 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:22089 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22089']/rh:substrates; rh:contains/rh:compound/rh:accession`
GTP `CHEBI:37565`	consumes	GTP pyrophosphokinase reaction `RHEA:22089`	RHEA:22089 Source assertion: Rhea lists CHEBI:37565 on the substrates side of RHEA:22089 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22089']/rh:substrates; rh:contains/rh:compound/rh:accession`
GTP pyrophosphokinase reaction `RHEA:22089`	produces	guanosine 3'-diphosphate 5'-triphosphate `CHEBI:142410`	RHEA:22089 Source assertion: Rhea lists CHEBI:142410 on the products side of RHEA:22089 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22089']/rh:products; rh:contains/rh:compound/rh:accession`
GTP pyrophosphokinase reaction `RHEA:22089`	produces	AMP `CHEBI:456215`	RHEA:22089 Source assertion: Rhea lists CHEBI:456215 on the products side of RHEA:22089 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/22089']/rh:products; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	ppGpp 3'-diphosphatase reaction `RHEA:14254`	RHEA:14254 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:14254 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14254']/rh:substrates; rh:contains/rh:compound/rh:accession`
guanosine 3',5'-bis(diphosphate) `CHEBI:77828`	consumes	ppGpp 3'-diphosphatase reaction `RHEA:14254`	RHEA:14254 Source assertion: Rhea lists CHEBI:77828 on the substrates side of RHEA:14254 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14254']/rh:substrates; rh:contains/rh:compound/rh:accession`
ppGpp 3'-diphosphatase reaction `RHEA:14254`	produces	H(+) `CHEBI:15378`	RHEA:14254 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:14254 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14254']/rh:products; rh:contains/rh:compound/rh:accession`
ppGpp 3'-diphosphatase reaction `RHEA:14254`	produces	diphosphate `CHEBI:33019`	RHEA:14254 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:14254 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14254']/rh:products; rh:contains/rh:compound/rh:accession`
ppGpp 3'-diphosphatase reaction `RHEA:14254`	produces	GDP `CHEBI:58189`	RHEA:14254 Source assertion: Rhea lists CHEBI:58189 on the products side of RHEA:14254 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/14254']/rh:products; rh:contains/rh:compound/rh:accession`
guanosine 3'-diphosphate 5'-triphosphate `CHEBI:142410`	consumes	pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	RHEA:13074 Source assertion: Rhea lists CHEBI:142410 on the substrates side of RHEA:13074 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13074']/rh:substrates; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	RHEA:13074 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:13074 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13074']/rh:substrates; rh:contains/rh:compound/rh:accession`
pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	produces	H(+) `CHEBI:15378`	RHEA:13074 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:13074 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13074']/rh:products; rh:contains/rh:compound/rh:accession`
pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	produces	phosphate `CHEBI:43474`	RHEA:13074 Source assertion: Rhea lists CHEBI:43474 on the products side of RHEA:13074 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13074']/rh:products; rh:contains/rh:compound/rh:accession`
pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	produces	guanosine 3',5'-bis(diphosphate) `CHEBI:77828`	RHEA:13074 Source assertion: Rhea lists CHEBI:77828 on the products side of RHEA:13074 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/13074']/rh:products; rh:contains/rh:compound/rh:accession`
nucleoside-diphosphate kinase `EC:2.7.4.6`	catalyzes	GDP kinase reaction `RHEA:27687`	RHEA:27686 Source assertion: Rhea associates EC:2.7.4.6 with the reaction family containing RHEA:27687. Source location `rh:ec`
guanosine-3',5'-bis(diphosphate) 3'-diphosphatase `EC:3.1.7.2`	catalyzes	guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	RHEA:33055 Source assertion: Rhea associates EC:3.1.7.2 with the reaction family containing RHEA:33056. Source location `rh:ec`
GTP diphosphokinase `EC:2.7.6.5`	catalyzes	GDP pyrophosphokinase reaction `RHEA:28099`	MetaCyc:PPGPPMET-PWY Source assertion: The native pathway assigns EC:2.7.6.5 activity to the enzymatic step represented by RHEA:28099; this is a component step when the EC definition is an overall reaction. Source location `Pathway/reaction-layout; Reaction/enzymatic-reaction and component-reaction relationships`
GTP diphosphokinase `EC:2.7.6.5`	catalyzes	GTP pyrophosphokinase reaction `RHEA:22089`	RHEA:22088 Source assertion: Rhea associates EC:2.7.6.5 with the reaction family containing RHEA:22089. Source location `rh:ec`
guanosine-3',5'-bis(diphosphate) 3'-diphosphatase `EC:3.1.7.2`	catalyzes	ppGpp 3'-diphosphatase reaction `RHEA:14254`	RHEA:14253 Source assertion: Rhea associates EC:3.1.7.2 with the reaction family containing RHEA:14254. Source location `rh:ec`
guanosine-5'-triphosphate,3'-diphosphate diphosphatase `EC:3.6.1.40`	catalyzes	pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	RHEA:13073 Source assertion: Rhea associates EC:3.6.1.40 with the reaction family containing RHEA:13074. Source location `rh:ec`
pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	precedes	ppGpp 3'-diphosphatase reaction `RHEA:14254`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:13074 before RHEA:14254 in this pathway. Shared intermediate: CHEBI:77828. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
ppGpp 3'-diphosphatase reaction `RHEA:14254`	precedes	GDP kinase reaction `RHEA:27687`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:14254 before RHEA:27687 in this pathway. Shared intermediate: CHEBI:58189. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
ppGpp 3'-diphosphatase reaction `RHEA:14254`	precedes	GDP pyrophosphokinase reaction `RHEA:28099`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:14254 before RHEA:28099 in this pathway. Shared intermediate: CHEBI:58189. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
GTP pyrophosphokinase reaction `RHEA:22089`	precedes	pppGpp 5'-phosphohydrolase reaction `RHEA:13074`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:22089 before RHEA:13074 in this pathway. Shared intermediate: CHEBI:142410. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
GTP pyrophosphokinase reaction `RHEA:22089`	precedes	guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:22089 before RHEA:33056 in this pathway. Shared intermediate: CHEBI:142410. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
GDP kinase reaction `RHEA:27687`	precedes	GTP pyrophosphokinase reaction `RHEA:22089`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:27687 before RHEA:22089 in this pathway. Shared intermediate: CHEBI:37565. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
GDP pyrophosphokinase reaction `RHEA:28099`	precedes	ppGpp 3'-diphosphatase reaction `RHEA:14254`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:28099 before RHEA:14254 in this pathway. Shared intermediate: CHEBI:77828. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction `RHEA:33056`	precedes	GTP pyrophosphokinase reaction `RHEA:22089`	MetaCyc:PPGPPMET-PWY Source assertion: MetaCyc pathway ordering places RHEA:33056 before RHEA:22089 in this pathway. Shared intermediate: CHEBI:37565. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`

References

MetaCyc:PPGPPMET-PWY MetaCyc ppGpp metabolism pathway (source version: 22.5)
RHEA:27686 Rhea GDP kinase reaction (source version: 139)
RHEA:27687 Rhea GTP-forming direction (source version: 139)
RHEA:33055 Rhea guanosine 3'-diphosphate 5'-triphosphate hydrolase reaction (source version: 139)
RHEA:33056 Rhea GTP-forming pppGpp hydrolase direction (source version: 139)
RHEA:28099 Rhea ppGpp-forming GDP pyrophosphokinase direction (source version: 139)
MetaCyc:GDPPYPHOSKIN-RXN MetaCyc GDP pyrophosphokinase reaction (source version: 22.5)
RHEA:22088 Rhea GTP pyrophosphokinase reaction (source version: 139)
RHEA:22089 Rhea pppGpp-forming direction (source version: 139)
RHEA:14253 Rhea ppGpp 3'-diphosphatase reaction (source version: 139)
RHEA:14254 Rhea GDP-forming ppGpp hydrolase direction (source version: 139)
RHEA:13073 Rhea pppGpp 5'-phosphohydrolase reaction (source version: 139)
RHEA:13074 Rhea ppGpp-forming pppGpp hydrolase 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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