Histidine catabolism to glutamate

A reusable pathway for degradation of L-histidine to L-glutamate. Three conserved reactions convert histidine through trans-urocanate and 4-imidazolone-5-propanoate to N-formimidoyl-L-glutamate. Terminal processing then differs among organisms. A two-step route uses HutF and HutG to release ammonium and formate; a one-step route uses a formimidoylglutamase to release formamide directly. The folate-coupled route instead transfers the formimino group to tetrahydrofolate and feeds it into one-carbon metabolism.

MODULE:histidine_catabolismDRAFTCONCRETEMetabolic Pathwaymodules/histidine_catabolism.yaml
L-histidine catabolic processGO:0006548
GO:0006548
L-histidine catabolic process
GO:0006548 captures degradation of L-histidine represented by the common three-step trunk and alternative terminal routes.
file:modules/histidine_catabolism-deep-research-openscientist.md
OpenScientist research for the reusable histidine catabolism module
The literature synthesis supports the ordered three-reaction trunk and the distinct two-step formate, one-step formamide, and folate-coupled terminal chemistries. It says an organism generally possesses one route, but treats identification of organisms with co-occurring routes as an open question. ONE_OR_MORE therefore avoids encoding an exclusivity constraint that the cited research has not established.
file:projects/P_PUTIDA/deep-research/PSEPK__histidine_catabolism__ppu00340-deep-research-openscientist.md
OpenScientist PSEPK histidine-catabolism satisfiability review
The taxon-specific synthesis supports coverage of the PSEPK route by HutH, HutU, HutI, HutF, and HutG, while explicitly noting that individual enzyme assignments rely mainly on reviewed records and congeneric evidence rather than direct KT2440 biochemistry for every step.
file:PSEPK/hutH/hutH-uniprot.txt
UniProtKB entry for PSEPK HutH
Q88CZ7 is a reviewed histidine ammonia-lyase assigned to Rhea 21232.
file:PSEPK/hutU/hutU-uniprot.txt
UniProtKB entry for PSEPK HutU
Q88CZ6 is a reviewed urocanate hydratase assigned to Rhea 13101.
file:PSEPK/hutI/hutI-uniprot.txt
UniProtKB entry for PSEPK HutI
Q88CZ9 is a reviewed imidazolonepropionase assigned to Rhea 23660.
RHEA:22832
formimidoylglutamate deiminase reaction
Rhea 22832 defines HutF-dependent formation of N-formyl-L-glutamate and ammonium.
RHEA:12476
N-formylglutamate deformylase reaction
Rhea 12476 defines HutG-dependent release of L-glutamate and formate.
RHEA:22492
formimidoylglutamase reaction
Rhea 22492 defines one-step hydrolysis of N-formimidoyl-L-glutamate to L-glutamate and formamide.
UniProtKB:P42068
Bacillus subtilis HutG formimidoylglutamase
The reviewed P42068 entry identifies Bacillus subtilis strain 168 HutG as formimidoylglutamase EC 3.5.3.8, assigns Rhea 22492, and cites PMID:4990470 for function and catalytic activity.
file:interpro/panther/PTHR11358/PTHR11358-entries.csv
PANTHER PTHR11358 member export
The committed PANTHER export classifies P42068 in the function-specific PTHR11358:SF35 FORMIMIDOYLGLUTAMASE subfamily.
InterPro:IPR005923
Formiminoglutamase family
IPR005923 is the function-specific Formiminoglutamase family and maps to formimidoylglutamase activity and histidine catabolism. The PANTHER subfamily complements rather than replaces this functional evidence by providing a locally validated member roster.
PMID:4990470
Urocanase and N-formimino-L-glutamate formiminohydrolase of Bacillus subtilis, two enzymes of the histidine degradation pathway.
Primary enzymology establishes the Bacillus subtilis N-formimino-L-glutamate formiminohydrolase as a histidine-degradation enzyme.
Urocanase and N-formimino-L-glutamate formiminohydrolase of Bacillus subtilis, two enzymes of the histidine degradation pathway.

This document replaces a one-part human-only wrapper. The common chemistry is now exposed as three ordered reaction parts and the terminal route is modeled explicitly as three implementation variants. The Pseudomonas putida KT2440 genes provide concrete exemplars for the two-step formate route, Bacillus subtilis HutG provides an exemplar for the one-step formamide route, and completed human reviews ground the folate-coupled FTCD route. These exemplars do not restrict the taxonomic scope of the route variants. Histidine transport, Hut transcriptional regulation, ammonia reassimilation, and downstream glutamate metabolism and folate one-carbon metabolism beyond the FTCD-intrinsic cyclodeamination are outside the boundary. The OpenScientist synthesis is retained as research provenance: it generally expects one terminal route but leaves coexistence unresolved. ONE_OR_MORE is a conservative relaxation that does not assert either exclusivity or parallel route occurrence.

12Nodes
8Parts
1Variant Sets
3Variants
8Annotons
5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • histidine_catabolism-deep-research-openscientist.md (openscientist)

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

11 gene-function check(s) reflected in core functions · 0 conflict(s) · 8 evidence or coverage gap(s) (20 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
huth_activity HutH (Pseudomonas putida KT2440)
UniProtKB:Q88CZ7
Family Representative 		histidine ammonia-lyase activity
GO:0004397 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
huth_activity HutH (Pseudomonas aeruginosa PAO1)
UniProtKB:Q9HU85
Family Representative 		histidine ammonia-lyase activity
GO:0004397 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
huth_activity HAL (human)
UniProtKB:P42357
Family Representative 		histidine ammonia-lyase activity
GO:0004397 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hutu_activity HutU (Pseudomonas putida KT2440)
UniProtKB:Q88CZ6
Family Representative 		urocanate hydratase activity
GO:0016153 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hutu_activity UROC1 (human)
UniProtKB:Q96N76
Family Representative 		urocanate hydratase activity
GO:0016153 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
huti_activity HutI (Pseudomonas putida KT2440)
UniProtKB:Q88CZ9
Family Representative 		imidazolonepropionase activity
GO:0050480 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
huti_activity AMDHD1 (human)
UniProtKB:Q96NU7
Family Representative 		imidazolonepropionase activity
GO:0050480 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hutf_activity HutF (Pseudomonas putida KT2440)
UniProtKB:Q88CZ3
Family Representative 		formimidoylglutamate deiminase activity
GO:0050416 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hutg_activity HutG (Pseudomonas putida KT2440)
UniProtKB:Q88D00
Family Representative 		N-formylglutamate deformylase activity
GO:0050129 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hutg_formimidoylglutamase_activity HutG (Bacillus subtilis)
UniProtKB:P42068
Family Representative 		formimidoylglutamase activity
GO:0050415 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ftcd_transferase_activity FTCD (human)
UniProtKB:O95954
Family Representative 		glutamate formimidoyltransferase activity
GO:0030409 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ftcd_cyclodeaminase_activity FTCD (human)
UniProtKB:O95954
Family Representative 		formimidoyltetrahydrofolate cyclodeaminase activity
GO:0030412 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
huth_activity histidine ammonia-lyase family
PANTHER:PTHR10362
Family 		histidine ammonia-lyase activity
GO:0004397 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR10362.
hutu_activity urocanate hydratase family
PANTHER:PTHR12216
Family 		urocanate hydratase activity
GO:0016153 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR12216.
huti_activity imidazolonepropionase family
PANTHER:PTHR42752
Family 		imidazolonepropionase activity
GO:0050480 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR42752.
hutf_activity HutF formimidoylglutamate deiminase family
InterPro:IPR010252
Family 		formimidoylglutamate deiminase activity
GO:0050416 		Family Review Missing
No supported structured family review is available for InterPro:IPR010252.
hutg_activity HutG N-formylglutamate deformylase family
InterPro:IPR010247
Family 		N-formylglutamate deformylase activity
GO:0050129 		Family Review Missing
No supported structured family review is available for InterPro:IPR010247.
hutg_formimidoylglutamase_activity formiminoglutamase family
PANTHER:PTHR11358:SF35
Family 		formimidoylglutamase activity
GO:0050415 		Family Supported
Family review supports GO:0050415 for PANTHER:PTHR11358:SF35. HutG (SF35), as histidine_catabolism selects.
ftcd_transferase_activity formimidoyltransferase-cyclodeaminase family
PANTHER:PTHR12234
Family 		glutamate formimidoyltransferase activity
GO:0030409 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR12234.
ftcd_cyclodeaminase_activity formimidoyltransferase-cyclodeaminase family
PANTHER:PTHR12234
Family 		formimidoyltetrahydrofolate cyclodeaminase activity
GO:0030412 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR12234.

Gene-review completeness (10/11 grounded genes reviewed)

10 complete review(s) · 1 with deep research · 1 missing review · 9 reviewed but lacking deep research

Gene Review Complete Deep research
AMDHD1 Q96NU7 ✓ ✓ ✗
FTCD O95954 ✓ ✓ ✗
HAL P42357 ✓ ✓ ✗
hutF Q88CZ3 ✓ ✓ ✗
hutG Q88D00 ✓ ✓ ✗
hutH Q88CZ7 ✓ ✓ ✗
hutH Q9HU85 ✓ ✓ ✗
hutI Q88CZ9 ✓ ✓ ✗
hutU Q88CZ6 ✓ ✓ ✓
HutG (Bacillus subtilis) P42068 ✗ — —
UROC1 Q96N76 ✓ ✓ ✗

Details

Histidine catabolism to glutamateMetabolic Pathwayhistidine_catabolism
L-histidine catabolic processGO:0006548

Connections

The urocanate produced by HutH/HAL is consumed by HutU/UROC1.
The imidazolone intermediate produced by HutU/UROC1 is consumed by HutI/AMDHD1.
N-formimidoyl-L-glutamate produced by HutI/AMDHD1 enters one of the terminal processing routes.
Part 1: histidine deamination
Histidine ammonia-lyase reactionReactionhistidine_to_urocanate

Annotons

HutH/HAL histidine ammonia-lyase activity
huth_activity
Participant: Family: histidine ammonia-lyase family
Family:
histidine ammonia-lyase familyPANTHER:PTHR10362
Representative Members: HutH (Pseudomonas putida KT2440)UniProtKB:Q88CZ7 HutH (Pseudomonas aeruginosa PAO1)UniProtKB:Q9HU85 HAL (human)UniProtKB:P42357

Function

histidine ammonia-lyase activityGO:0004397
Substrates: L-histidine
Products: trans-urocanate ammonium

Processes

L-histidine catabolic processGO:0006548

Commits L-histidine to the urocanate pathway.

Part 2: urocanate hydration
Urocanate hydratase reactionReactionurocanate_to_imidazolonepropanoate

Annotons

HutU/UROC1 urocanate hydratase activity
hutu_activity
Participant: Family: urocanate hydratase family
Family:
urocanate hydratase familyPANTHER:PTHR12216
Representative Members: HutU (Pseudomonas putida KT2440)UniProtKB:Q88CZ6 UROC1 (human)UniProtKB:Q96N76

Function

urocanate hydratase activityGO:0016153
Substrates: trans-urocanate water
Products: 4-imidazolone-5-propanoate

Processes

L-histidine catabolic processGO:0006548

Hydrates urocanate to the cyclic imidazolone intermediate.

Part 3: imidazolone ring opening
Imidazolonepropionase reactionReactionimidazolonepropanoate_to_figlu

Annotons

HutI/AMDHD1 imidazolonepropionase activity
huti_activity
Participant: Family: imidazolonepropionase family
Family:
imidazolonepropionase familyPANTHER:PTHR42752
Representative Members: HutI (Pseudomonas putida KT2440)UniProtKB:Q88CZ9 AMDHD1 (human)UniProtKB:Q96NU7

Function

imidazolonepropionase activityGO:0050480
Substrates: 4-imidazolone-5-propanoate water
Products: N-formimidoyl-L-glutamate

Processes

L-histidine catabolic processGO:0006548

Produces FIGLU, the branch point for terminal processing.

Part 4: terminal FIGLU processing to L-glutamate
Alternative terminal processing of N-formimidoyl-L-glutamateMetabolic Pathwayfiglu_terminal_processing
Variant set: FIGLU terminal-processing routes by formimino-group disposal (One Or More)

A complete pathway realization requires at least one terminal chemistry and may contain parallel routes. The exemplar taxa do not define route boundaries.

Two-step HutF/HutG formate routeMetabolic Pathwaytwo_step_formate_route

Connections

HutF produces the N-formyl-L-glutamate consumed by HutG.
Part 1: FIGLU deimination
HutF-dependent N-formyl-L-glutamate formationReactionhutf_n_formylglutamate_formation

Annotons

HutF formimidoylglutamate deiminase activity
hutf_activity
Participant: Family: HutF formimidoylglutamate deiminase family
Family:
HutF formimidoylglutamate deiminase familyInterPro:IPR010252
Representative Members: HutF (Pseudomonas putida KT2440)UniProtKB:Q88CZ3

Function

formimidoylglutamate deiminase activityGO:0050416
Substrates: N-formimidoyl-L-glutamate water
Products: N-formyl-L-glutamate ammonium

Processes

L-histidine catabolic processGO:0006548

Produces N-formyl-L-glutamate and ammonium.

Part 2: N-formyl-L-glutamate deformylation
HutG-dependent L-glutamate and formate formationReactionhutg_glutamate_formation

Annotons

HutG N-formylglutamate deformylase activity
hutg_activity
Participant: Family: HutG N-formylglutamate deformylase family
Family:
HutG N-formylglutamate deformylase familyInterPro:IPR010247
Representative Members: HutG (Pseudomonas putida KT2440)UniProtKB:Q88D00

Function

N-formylglutamate deformylase activityGO:0050129
Substrates: N-formyl-L-glutamate water
Products: L-glutamate formate

Processes

L-histidine catabolic processGO:0006548

Releases the glutamate and formate outputs.

One-step formimidoylglutamase routeReactionone_step_formamide_route

Annotons

Formimidoylglutamase activity
hutg_formimidoylglutamase_activity
Participant: Family: formiminoglutamase family
Family:
formiminoglutamase familyPANTHER:PTHR11358:SF35
Representative Members: HutG (Bacillus subtilis)UniProtKB:P42068

Function

formimidoylglutamase activityGO:0050415
Substrates: N-formimidoyl-L-glutamate water
Products: L-glutamate formamide

Processes

L-histidine catabolic processGO:0006548

Releases glutamate and formamide directly from FIGLU.

Folate-coupled FTCD routeMetabolic Pathwayfolate_coupled_route

Connections

The 5-formimidoyltetrahydrofolate produced by the transferase reaction is consumed by cyclodeamination.
Part 1: formimino transfer to tetrahydrofolate
FTCD glutamate formimidoyltransferase reactionReactionftcd_formimino_transfer

Annotons

FTCD glutamate formimidoyltransferase activity
ftcd_transferase_activity
Participant: Family: formimidoyltransferase-cyclodeaminase family
Family:
formimidoyltransferase-cyclodeaminase familyPANTHER:PTHR12234
Representative Members: FTCD (human)UniProtKB:O95954

Function

glutamate formimidoyltransferase activityGO:0030409
Substrates: N-formimidoyl-L-glutamate tetrahydrofolate
Products: L-glutamate 5-formimidoyltetrahydrofolate

Processes

L-histidine catabolic processGO:0006548

Releases glutamate and transfers the one-carbon unit to folate.

Part 2: formimino-folate cyclodeamination
FTCD formimidoyltetrahydrofolate cyclodeaminase reactionReactionftcd_cyclodeamination

Annotons

FTCD formimidoyltetrahydrofolate cyclodeaminase activity
ftcd_cyclodeaminase_activity
Participant: Family: formimidoyltransferase-cyclodeaminase family
Family:
formimidoyltransferase-cyclodeaminase familyPANTHER:PTHR12234
Representative Members: FTCD (human)UniProtKB:O95954

Function

formimidoyltetrahydrofolate cyclodeaminase activityGO:0030412
Substrates: 5-formimidoyltetrahydrofolate
Products: 5,10-methenyltetrahydrofolate ammonium

Feeds the histidine-derived one-carbon unit into the folate pool.