Homogentisate catabolism

A reusable three-reaction pathway that opens the aromatic ring of homogentisate to form maleylacetoacetate, isomerizes maleylacetoacetate to fumarylacetoacetate, and hydrolyzes fumarylacetoacetate to fumarate and acetoacetate. This lower pathway accepts homogentisate from multiple upstream aromatic-substrate routes and ends at metabolites that can enter central carbon metabolism.

MODULE:homogentisate_catabolismDRAFTMetabolic Pathwaymodules/homogentisate_catabolism.yaml
homogentisate catabolic processGO:1902000
GO:1902000
homogentisate catabolic process
GO:1902000 defines the biological-process boundary from homogentisate consumption through lower-pathway products.
file:modules/homogentisate_catabolism-deep-research-openscientist.md
OpenScientist research for the reusable homogentisate-catabolism module
The module-level review supports the ordered HmgA-HmgC-HmgB lower pathway and distinguishes its boundaries from upstream aromatic-substrate routes and downstream central metabolism.
file:projects/P_PUTIDA/deep-research/PSEPK__homogentisate_catabolism__ppu00643-deep-research-openscientist.md
OpenScientist PSEPK/ppu00643 homogentisate-catabolism research
The KT2440 pathway review finds all three lower-pathway reactions covered by the contiguous hmgABC genes and identifies peaE and PP_2932 as overview-map artifacts outside the homogentisate module boundary.
file:PSEPK/hmgA/hmgA-ai-review.yaml
PSEPK hmgA gene review
The curated KT2440 review identifies Q88E47 as an iron-dependent homogentisate 1,2-dioxygenase and separates its enzymatic role from misassigned transcription-regulator annotations.
file:PSEPK/hmgC/hmgC-ai-review.yaml
PSEPK hmgC gene review
The curated KT2440 review identifies Q88E49 as the glutathione-dependent maleylacetoacetate isomerase.
file:PSEPK/hmgB/hmgB-ai-review.yaml
PSEPK hmgB gene review
The curated KT2440 review identifies Q88E48 as the terminal fumarylacetoacetase.
file:PSEPK/hmgB/hmgB-uniprot.txt
UniProtKB entry Q88E48 for PSEPK HmgB
UniProt assigns calcium or magnesium as alternative divalent cofactors for the Q88E48 fumarylacetoacetase.
PMID:15262943
The homogentisate pathway: a central catabolic pathway involved in the degradation of L-phenylalanine, L-tyrosine, and 3-hydroxyphenylacetate in Pseudomonas putida.
The organism-specific study identifies HmgA, HmgC, and HmgB as the three enzymes that convert homogentisate to fumarate and acetoacetate.
4Nodes
3Parts
0Variant Sets
0Variants
3Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • homogentisate_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.

Gene-review completeness (3/3 grounded genes reviewed)

3 complete review(s) · 3 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
hmgA Q88E47 ✓ ✓ ✓
hmgB Q88E48 ✓ ✓ ✓
hmgC Q88E49 ✓ ✓ ✓

Details

Homogentisate catabolismMetabolic Pathwayhomogentisate_catabolism
homogentisate catabolic processGO:1902000

The module begins at homogentisate so that phenylalanine, tyrosine, 3-hydroxyphenylacetate, and other upstream routes can connect without being treated as required parts. Exact KT2440 accessions serve as representative members and do not restrict the module to Pseudomonas. A nonenzymatic glutathione-mediated maleylacetoacetate isomerization bypass has been reported in MAAI-deficient mammalian contexts; it is not modeled here as a general enzymatic variant because HmgC is the canonical biological implementation of this step.

Connections

HmgA produces maleylacetoacetate for HmgC.
HmgC produces fumarylacetoacetate for HmgB.
Part 1: homogentisate ring cleavage
Homogentisate oxidative ring cleavageReactionhomogentisate_ring_cleavage

Annotons

Homogentisate 1,2-dioxygenase
homogentisate_dioxygenase
Participant: Family: HmgA homogentisate 1,2-dioxygenases
Family:
HmgA homogentisate 1,2-dioxygenases
Representative Members: PSEPK HmgAUniProtKB:Q88E47

Function

homogentisate 1,2-dioxygenase activityGO:0004411
Substrates: homogentisate dioxygen
Products: maleylacetoacetate
Cofactors: iron ion

Performs oxidative aromatic-ring cleavage to create the open-chain maleylacetoacetate intermediate.

Part 2: maleylacetoacetate isomerization
Maleylacetoacetate isomerizationReactionmaleylacetoacetate_isomerization

Annotons

Maleylacetoacetate isomerase
maleylacetoacetate_isomerase
Participant: Family: HmgC maleylacetoacetate isomerases
Family:
HmgC maleylacetoacetate isomerases
Representative Members: PSEPK HmgCUniProtKB:Q88E49

Function

maleylacetoacetate isomerase activityGO:0016034
Substrates: maleylacetoacetate
Products: fumarylacetoacetate
Cofactors: glutathione

Converts the cis-like maleyl intermediate to the fumaryl intermediate used by HmgB.

Part 3: fumarylacetoacetate hydrolysis
Fumarylacetoacetate hydrolysisReactionfumarylacetoacetate_hydrolysis

Annotons

Fumarylacetoacetase
fumarylacetoacetase
Participant: Family: HmgB fumarylacetoacetases
Family:
HmgB fumarylacetoacetases
Representative Members: PSEPK HmgBUniProtKB:Q88E48

Function

fumarylacetoacetase activityGO:0004334
Substrates: fumarylacetoacetate H2O
Products: fumarate acetoacetate
Cofactors: calcium or magnesium ion

Releases fumarate and acetoacetate for entry into central carbon metabolism.