Gamma-glutamyl putrescine catabolism to 4-aminobutanoate

A four-reaction route in which putrescine is activated by ATP-dependent gamma-glutamylation, oxidized to a gamma-glutamyl aminoaldehyde, oxidized again to gamma-glutamyl-4-aminobutanoate, and hydrolyzed to release 4-aminobutanoate (GABA) and glutamate. Putrescine supply and import, the parallel non-glutamylated transaminase route, and the downstream GABA shunt are separate modules.

MODULE:gamma_glutamyl_putrescine_catabolismDRAFTCONCRETEMetabolic Pathwaymodules/gamma_glutamyl_putrescine_catabolism.yaml
putrescine catabolic processGO:0009447
GO:0009447
putrescine catabolic process
Defines the substrate-specific catabolic process represented here.
RHEA:13633
glutamate-putrescine ligase reaction
Defines ATP-dependent gamma-glutamylputrescine formation.
RHEA:28414
gamma-glutamylputrescine oxidoreductase reaction
Defines oxidative formation of the gamma-glutamyl aminoaldehyde.
RHEA:28410
NADP-dependent PuuC reaction
Defines one experimentally supported cofactor variant of gamma-glutamyl aminoaldehyde oxidation.
RHEA:42340
NAD-dependent PuuC reaction
Defines the alternative experimentally supported cofactor variant of gamma-glutamyl aminoaldehyde oxidation.
RHEA:19737
gamma-glutamyl-gamma-aminobutyrate hydrolase reaction
Defines hydrolytic release of GABA and glutamate.
PANTHER:PTN000230196
PAINT bacterial PuuD ancestral node
The local PTHR43235 PAINT table assigns GO:0033969 and GO:0006598 to PTN000230196 using experimentally characterized E. coli PuuD P76038 as a seed.
PMID:18495664
gamma-Glutamylputrescine synthetase in the putrescine utilization pathway of Escherichia coli K-12.
Biochemically establishes the PuuA reaction and its distinction from glutamine synthetase activity.
PMID:15590624
A novel putrescine utilization pathway involves gamma-glutamylated intermediates of Escherichia coli K-12.
Defines the sequential PuuA-PuuB-PuuC-PuuD chemistry represented by the module.
PMID:12081945
Functional analysis and regulation of the divergent spuABCDEFGH-spuI operons for polyamine uptake and utilization in Pseudomonas aeruginosa PAO1.
Provides comparative Pseudomonas operon and SpuC transaminase evidence used to set the module boundary.
PMID:18192388
Transcriptome analysis of agmatine and putrescine catabolism in Pseudomonas aeruginosa PAO1.
Establishes the SpuC transaminase route as major and gamma-glutamylation as an alternative Pseudomonas route.
file:projects/P_PUTIDA/deep-research/PSEPK__gamma-glutamyl-putrescine-catabolism__ppu00330-deep-research-openscientist.md
OpenScientist PSEPK gamma-glutamyl putrescine catabolism synthesis
Species-aware retrieval identifies strong KT2440 PuuA, PuuB, and PuuD implementations and PP_2589 as the leading but incompletely resolved PuuC candidate.

KT2440 PuuA candidates are Q88KW1 and Q88C84, with additional glutamylpolyamine synthetases nearby. Q88K44 is the exact PuuB-subfamily candidate. Q88JR0 carries a PuuC/GABA-aldehyde-dehydrogenase CDD assignment and the relevant KEGG orthology, but its UniProt function remains generic; this step is therefore candidate-uncertain in the target organism. PuuD candidates Q88C85, Q88KW0, and Q88GW9 carry exact EC 3.5.1.94 assignments. Comparative P. aeruginosa evidence indicates that SpuC transamination is the major putrescine route, so this module does not imply dominant KT2440 flux.

5Nodes
4Parts
0Variant Sets
0Variants
4Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:gamma_glutamyl_putrescine_catabolism deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

4 gene-function check(s) reflected in core functions · 0 conflict(s) · 14 evidence or coverage gap(s) (18 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
puuA_activity PSEPK PuuA-I
UniProtKB:Q88KW1
Family Representative
glutamate-putrescine ligase activity
GO:0034024
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
puuA_activity PSEPK PuuA-II
UniProtKB:Q88C84
Family Representative
glutamate-putrescine ligase activity
GO:0034024
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
puuA_activity E. coli PuuA
UniProtKB:P78061
Family Representative
glutamate-putrescine ligase activity
GO:0034024
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
puuB_activity PSEPK PuuB
UniProtKB:Q88K44
Family Representative
gamma-glutamylputrescine oxidase activity
No function ID
No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
puuB_activity E. coli PuuB
UniProtKB:P37906
Family Representative
gamma-glutamylputrescine oxidase activity
No function ID
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked. The module function also lacks a GO identifier.
puuB_activity:required_function PSEPK PuuB
UniProtKB:Q88K44
Family Representative
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor
GO:0016641
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
puuB_activity:required_function E. coli PuuB
UniProtKB:P37906
Family Representative
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor
GO:0016641
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
puuC_activity PSEPK PP_2589 candidate
UniProtKB:Q88JR0
Family Representative
aldehyde dehydrogenase [NAD(P)+] activity
GO:0004030
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
puuC_activity E. coli PuuC
UniProtKB:P23883
Family Representative
aldehyde dehydrogenase [NAD(P)+] activity
GO:0004030
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
puuD_activity PSEPK PP_5298
UniProtKB:Q88C85
Family Representative
gamma-glutamyl-gamma-aminobutyrate hydrolase activity
GO:0033969
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
puuD_activity PSEPK SpuA
UniProtKB:Q88KW0
Family Representative
gamma-glutamyl-gamma-aminobutyrate hydrolase activity
GO:0033969
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
puuD_activity PSEPK PP_3598
UniProtKB:Q88GW9
Family Representative
gamma-glutamyl-gamma-aminobutyrate hydrolase activity
GO:0033969
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
puuD_activity E. coli PuuD
UniProtKB:P76038
Family Representative
gamma-glutamyl-gamma-aminobutyrate hydrolase activity
GO:0033969
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
puuA_activity gamma-glutamylputrescine synthetase family
PANTHER:PTHR43785
Family
glutamate-putrescine ligase activity
GO:0034024
Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0034024.
puuB_activity gamma-glutamylputrescine oxidoreductase subfamily
PANTHER:PTHR13847:SF275
Family
gamma-glutamylputrescine oxidase activity
No function ID
No Function Id
The family function has no GO identifier for comparison; prose is not matched.
puuB_activity:required_function gamma-glutamylputrescine oxidoreductase subfamily
PANTHER:PTHR13847:SF275
Family
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor
GO:0016641
Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0016641.
puuC_activity PuuC-like aldehyde dehydrogenases
PANTHER:PTHR11699
Family
aldehyde dehydrogenase [NAD(P)+] activity
GO:0004030
Family Function Unreviewed
Family review leaves GO:0004029 UNRESOLVED. Sound where PAINT scopes it (the PTN000192666 clade minus the ALDH1L branch flagged for pruning), but not safe family-wide and not expressible with the available scoping axes. Not FAMILY_WIDE: the family also holds NADP(+)-preferring members -- the ALDH1L/FDH clade (SF120, SF131), whose intact ALDH domain is strictly NADP+-dependent and whose in-repo rat Aldh1l1 gene review MODIFYs this exact term to GO:0033721, and the subfamily officially named "SUCCINATE-SEMIALDEHYDE DEHYDROGENASE [NADP(+)] 2-RELATED" -- plus CoA-acylating EutE-type enzymes whose chemistry the term does not describe, and the degenerate ALDH16A1. Not RESIDUE_DETERMINED: retention of the catalytic cysteine is necessary but does not determine NAD+ versus NADP+ cofactor specificity, so a residue site alone would over-grant the NAD+-specific term. Not SUBFAMILY_ONLY: the family has ~47 subfamilies, many genuinely NAD+-dependent (ALDH2, ALDH1A1, ALDH1B1, ALDH9A1, yeast and bacterial members), and enumerating every safe subfamily is beyond this review's scope. The practical guidance is per-node, as PAINT already does it: inherit from PTN000192666 (with the ALDH1L branch pruned), and treat as a non-core generic parent for substrate-specialized members such as the ALDH1A branch.
puuD_activity PuuD-like peptidase C26 family
PANTHER:PTHR43235
Family
gamma-glutamyl-gamma-aminobutyrate hydrolase activity
GO:0033969
Family Review Missing
No supported structured family review is available for PANTHER:PTHR43235.

Gene-review completeness (4/11 grounded genes reviewed)

4 complete review(s) · 0 with deep research · 7 missing review · 4 reviewed but lacking deep research

Gene Review Complete Deep research
E. coli PuuC P23883 ✗ — —
E. coli PuuB P37906 ✗ — —
E. coli PuuD P76038 ✗ — —
E. coli PuuA P78061 ✗ — —
PP_2589 Q88JR0 ✓ ✓ ✗
PP_5298 Q88C85 ✓ ✓ ✗
puuA-I Q88KW1 ✓ ✓ ✗
puuB Q88K44 ✓ ✓ ✗
PSEPK PuuA-II Q88C84 ✗ — —
PSEPK PP_3598 Q88GW9 ✗ — —
PSEPK SpuA Q88KW0 ✗ — —

Details

Gamma-glutamyl putrescine catabolism to GABAMetabolic Pathwaygamma_glutamyl_putrescine_catabolism
putrescine catabolic processGO:0009447

Connections

puuA_reaction -> puuB_reaction Provides Input For
puuB_reaction -> puuC_reaction Provides Input For
puuC_reaction -> puuD_reaction Provides Input For
Part 1: putrescine gamma-glutamylation
Putrescine to gamma-glutamylputrescineReactionpuuA_reaction

Annotons

Glutamate-putrescine ligase
puuA_activity
Participant: Family: gamma-glutamylputrescine synthetase family
Family:
gamma-glutamylputrescine synthetase familyPANTHER:PTHR43785
Representative Members: PSEPK PuuA-IUniProtKB:Q88KW1 PSEPK PuuA-IIUniProtKB:Q88C84 E. coli PuuAUniProtKB:P78061
Required Function:
glutamate-putrescine ligase activityGO:0034024

Function

glutamate-putrescine ligase activityGO:0034024
Substrates: putrescine L-glutamate ATP
Products: gamma-L-glutamylputrescine ADP phosphate

Processes

putrescine catabolic processGO:0009447

Committed activation of putrescine by gamma-glutamylation.

Part 2: gamma-glutamylputrescine oxidation
Gamma-glutamylputrescine to gamma-glutamyl aminoaldehydeReactionpuuB_reaction

Annotons

Gamma-glutamylputrescine oxidase
puuB_activity
Participant: Family: gamma-glutamylputrescine oxidoreductase subfamily
Family:
gamma-glutamylputrescine oxidoreductase subfamilyPANTHER:PTHR13847:SF275
Representative Members: PSEPK PuuBUniProtKB:Q88K44 E. coli PuuBUniProtKB:P37906
Required Function:
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptorGO:0016641

Function

gamma-glutamylputrescine oxidase activity
Substrates: gamma-L-glutamylputrescine oxygen water
Products: 4-(gamma-L-glutamylamino)butanal hydrogen peroxide ammonium

Processes

putrescine catabolic processGO:0009447

FAD-family oxidation of the gamma-glutamylated diamine.

Part 3: gamma-glutamyl aminoaldehyde oxidation
Gamma-glutamyl aminoaldehyde to gamma-glutamyl-GABAReactionpuuC_reaction

Annotons

Gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase
puuC_activity
Participant: Family: PuuC-like aldehyde dehydrogenases
Family:
PuuC-like aldehyde dehydrogenasesPANTHER:PTHR11699
Representative Members: PSEPK PP_2589 candidateUniProtKB:Q88JR0 E. coli PuuCUniProtKB:P23883
Required Function:
aldehyde dehydrogenase [NAD(P)+] activityGO:0004030

Function

aldehyde dehydrogenase [NAD(P)+] activityGO:0004030
Substrates: 4-(gamma-L-glutamylamino)butanal NAD+ or NADP+ water
Products: 4-(gamma-L-glutamylamino)butanoate NADH or NADPH protons

Processes

putrescine catabolic processGO:0009447

Oxidizes the gamma-glutamyl aminoaldehyde; the exact KT2440 locus remains candidate-uncertain.

Part 4: gamma-glutamyl-GABA hydrolysis
Gamma-glutamyl-GABA to GABA and glutamateReactionpuuD_reaction

Annotons

Gamma-glutamyl-gamma-aminobutyrate hydrolase
puuD_activity
Participant: Family: PuuD-like peptidase C26 family
Family:
PuuD-like peptidase C26 familyPANTHER:PTHR43235
Representative Members: PSEPK PP_5298UniProtKB:Q88C85 PSEPK SpuAUniProtKB:Q88KW0 PSEPK PP_3598UniProtKB:Q88GW9 E. coli PuuDUniProtKB:P76038
Required Function:
gamma-glutamyl-gamma-aminobutyrate hydrolase activityGO:0033969

Function

gamma-glutamyl-gamma-aminobutyrate hydrolase activityGO:0033969
Substrates: 4-(gamma-L-glutamylamino)butanoate water
Products: 4-aminobutanoate L-glutamate

Processes

putrescine catabolic processGO:0009447

Removes the gamma-glutamyl group and releases GABA for downstream metabolism.