Reductive pyrimidine degradation

A reusable three-reaction pathway for reductive degradation of uracil and thymine. Dihydropyrimidine dehydrogenase first reduces the pyrimidine ring, dihydropyrimidinase opens the saturated ring, and beta-ureidopropionase releases beta-alanine or beta-aminoisobutyrate, carbon dioxide, and ammonium. The pathway chemistry is conserved, but the first and third enzymes have distinct taxonomic implementations.

MODULE:pyrimidine_degradationDRAFTCONCRETEMetabolic Pathwaymodules/pyrimidine_degradation.yaml

pyrimidine nucleobase catabolic processGO:0006208

GO:0006208

pyrimidine nucleobase catabolic process

GO:0006208 captures degradation of uracil and thymine represented by this three-reaction pathway.

file:PSEPK/pydA/pydA-ai-review.yaml

PSEPK pydA gene review

Q88FQ0 contributes to the heteromeric PydXA dihydropyrimidine dehydrogenase required for uracil and thymine utilization.

file:PSEPK/pydX/pydX-ai-review.yaml

PSEPK pydX gene review

Q88FQ1 is the NADH-oxidizing flavin/iron-sulfur partner subunit of the same PydXA enzyme; its specific flavin remains unresolved.

file:PSEPK/pydB/pydB-ai-review.yaml

PSEPK pydB gene review

A0A140FWK2 is the zinc-dependent dihydropyrimidinase performing the second reaction.

file:PSEPK/hyuC/hyuC-ai-review.yaml

PSEPK hyuC gene review

Q88FQ3 is a candidate terminal beta-ureidopropionase near the PSEPK pyd locus, but beta-ureidopropionate, allantoate, and N-carbamoyl-L-amino-acid specificities remain unresolved.

This revision preserves the previously curated human route while adding the bacterial PydXA and HyuC implementations. The module is drawn with the uracil-to-beta-alanine branch; thymine follows the same three roles to beta-aminoisobutyrate. In PSEPK, Q88FQ3 and PP_0614/Q88Q81 are unresolved candidates for the terminal reaction. PTHR32494 membership alone does not establish beta-ureidopropionase activity, so the bacterial HyuC variant below requires independent function evidence. Pyrimidine nucleotide dephosphorylation, base transport, beta-alanine utilization, CoA synthesis, and fluoropyrimidine pharmacology are outside the core.

8Nodes

3Parts

2Variant Sets

4Variants

5Annotons

2Connections

Derived QC

Recommended-field compliance

55.6% recommended fields populated

module.knowledge_gaps[0] · status (0/1)
module.knowledge_gaps[0] · provenance (0/1)
module.knowledge_gaps[1] · status (0/1)
module.knowledge_gaps[1] · provenance (0/1)

Module deep research

✗ none found

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

Leaf nodes lacking representative members

1 leaf node(s) with no concrete protein grounding:

Candidate bacterial HyuC-family implementation FAMILY

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (6/6 grounded genes reviewed)

6 complete review(s) · 1 with deep research · 0 missing review · 5 reviewed but lacking deep research

Gene	Review	Complete	Deep research
DPYD Q12882	✓	✓	✗
DPYS Q14117	✓	✓	✗
pydA Q88FQ0	✓	✓	✗
pydB A0A140FWK2	✓	✓	✗
pydX Q88FQ1	✓	✓	✓
UPB1 Q9UBR1	✓	✓	✗

Tree

Reductive pyrimidine degradationMetabolic Pathwaypyrimidine_degradation

Parts
1. 1. pyrimidine-ring reduction
2. Alternative dihydropyrimidine dehydrogenase implementationsReactiondihydropyrimidine_formation
  
  Variants
  1. Dihydropyrimidine dehydrogenase implementations by enzyme architecture and nicotinamide cofactor (Exactly One)
    
    Bacterial heteromeric PydXA using NADHReactionbacterial_pydxa_variant
    
    Annotons
    
    PydXA dihydropyrimidine dehydrogenase (NAD+) activity Protein Complex: bacterial PydXA dihydropyrimidine dehydrogenase
    
    Eukaryotic single-chain DPYD using NADPHReactioneukaryotic_dpyd_variant
    
    Annotons
    
    DPYD dihydropyrimidine dehydrogenase (NADP+) activity Family: DPYD family
3. 2. dihydropyrimidine ring opening
4. Dihydropyrimidinase reactionReactionureidopropionate_formation
  
  Annotons
  - PydB/DPYS dihydropyrimidinase activity Family: dihydropyrimidinase family
5. 3. beta-alanine formation
6. Alternative beta-ureidopropionase implementationsReactionbeta_alanine_formation
  
  Variants
  1. Beta-ureidopropionase family variants by enzyme family (Exactly One)
    
    Candidate bacterial HyuC-family implementationReactionbacterial_hyuc_variant
    
    Annotons
    
    Function-constrained HyuC-family beta-ureidopropionase Family: HyuC metal-dependent amidohydrolase family
    
    Eukaryotic nitrilase-family beta-ureidopropionaseReactionnitrilase_upb1_variant
    
    Annotons
    
    UPB1 beta-ureidopropionase activity Family: nitrilase-family beta-ureidopropionase

Details

Reductive pyrimidine degradationMetabolic Pathwaypyrimidine_degradation

pyrimidine nucleobase catabolic processGO:0006208

Connections

dihydropyrimidine_formation -> ureidopropionate_formation Provides Input For

Either first-step implementation produces dihydrouracil for ring opening.

ureidopropionate_formation -> beta_alanine_formation Provides Input For

Dihydropyrimidinase supplies ureidopropionate to either terminal enzyme.

Part 1: pyrimidine-ring reduction

Alternative dihydropyrimidine dehydrogenase implementationsReactiondihydropyrimidine_formation

Variant set: Dihydropyrimidine dehydrogenase implementations by enzyme architecture and nicotinamide cofactor (Exactly One)

Bacterial heteromeric PydXA using NADHReactionbacterial_pydxa_variant

Context

bacteriaNCBITaxon:2

Annotons

PydXA dihydropyrimidine dehydrogenase (NAD+) activity

pydxa_activity

Participant: Protein Complex: bacterial PydXA dihydropyrimidine dehydrogenase

Protein Complex:

bacterial PydXA dihydropyrimidine dehydrogenase

Active units:

PydA iron-sulfur flavoprotein subunit

Participant: Family: PydA dihydropyrimidine dehydrogenase subunit family

Family:

PydA dihydropyrimidine dehydrogenase subunit familyPANTHER:PTHR43073

Representative Members: PydA (Pseudomonas putida KT2440)UniProtKB:Q88FQ0

Required Domain:

dihydroorotate-dehydrogenase-like catalytic domainInterPro:IPR005720

Role: Contributes iron-sulfur redox chemistry to the assembled heteromeric dehydrogenase.

PydX flavin/iron-sulfur partner subunit

Participant: Family: PydX dihydropyrimidine dehydrogenase subunit family

Family:

PydX dihydropyrimidine dehydrogenase subunit familyPANTHER:PTHR43073

Representative Members: PydX (Pseudomonas putida KT2440)UniProtKB:Q88FQ1

Required Domain:

dihydropyrimidine dehydrogenase domain IIInterPro:IPR028261

Role: Transfers reducing equivalents and contributes to catalysis in the assembled enzyme.

Function

dihydropyrimidine dehydrogenase (NAD+) activityGO:0004159

Substrates: uracil NADH

Products: 5,6-dihydrouracil NAD+

Processes

pyrimidine-containing compound catabolic processGO:0072529

Performs NADH-dependent pyrimidine reduction as a heteromer.

Eukaryotic single-chain DPYD using NADPHReactioneukaryotic_dpyd_variant

Context

eukaryotesNCBITaxon:2759

Annotons

DPYD dihydropyrimidine dehydrogenase (NADP+) activity

dpyd_activity

Participant: Family: DPYD family

Family:

DPYD familyPANTHER:PTHR43073

Representative Members: DPYD (human)UniProtKB:Q12882

Function

dihydropyrimidine dehydrogenase (NADP+) activityGO:0017113

Substrates: uracil NADPH

Products: 5,6-dihydrouracil NADP+

Processes

pyrimidine nucleobase catabolic processGO:0006208

Performs NADPH-dependent pyrimidine reduction in one chain.

Part 2: dihydropyrimidine ring opening

Dihydropyrimidinase reactionReactionureidopropionate_formation

Annotons

PydB/DPYS dihydropyrimidinase activity

dpys_pydB_activity

Participant: Family: dihydropyrimidinase family

Family:

dihydropyrimidinase familyPANTHER:PTHR11647

Representative Members: PydB (Pseudomonas putida KT2440)UniProtKB:A0A140FWK2 DPYS (human)UniProtKB:Q14117

Required Domain:

hydantoinase/dihydropyrimidinase domainInterPro:IPR011778

Function

dihydropyrimidinase activityGO:0004157

Substrates: 5,6-dihydrouracil water

Products: 3-(carbamoylamino)propanoate

Processes

pyrimidine nucleobase catabolic processGO:0006208

Opens the reduced pyrimidine ring to form ureidopropionate.

Part 3: beta-alanine formation

Alternative beta-ureidopropionase implementationsReactionbeta_alanine_formation

Variant set: Beta-ureidopropionase family variants by enzyme family (Exactly One)

Candidate bacterial HyuC-family implementationReactionbacterial_hyuc_variant

Context

bacteriaNCBITaxon:2

Annotons

Function-constrained HyuC-family beta-ureidopropionase

hyuc_activity

Participant: Family: HyuC metal-dependent amidohydrolase family

Family:

HyuC metal-dependent amidohydrolase familyPANTHER:PTHR32494

Required Function:

independently supported beta-ureidopropionase activityGO:0003837

Function

beta-ureidopropionase activityGO:0003837

Substrates: 3-(carbamoylamino)propanoate water

Products: beta-alanine ammonium carbon dioxide

Processes

pyrimidine-containing compound catabolic processGO:0072529

Candidate bacterial implementation restricted to PTHR32494 members with beta-ureidopropionase function established independently of family membership.

Eukaryotic nitrilase-family beta-ureidopropionaseReactionnitrilase_upb1_variant

Context

eukaryotesNCBITaxon:2759

Annotons

UPB1 beta-ureidopropionase activity

upb1_activity

Participant: Family: nitrilase-family beta-ureidopropionase

Family:

nitrilase-family beta-ureidopropionasePANTHER:PTHR43674

Representative Members: UPB1 (human)UniProtKB:Q9UBR1

Required Function:

beta-ureidopropionase activityGO:0003837

Function

beta-ureidopropionase activityGO:0003837

Substrates: 3-(carbamoylamino)propanoate water

Products: beta-alanine ammonium carbon dioxide

Processes

pyrimidine nucleobase catabolic processGO:0006208

Completes the route with a nitrilase-family enzyme.