Pyrimidine nucleotide catabolism (5'-nucleotidase/deaminase/phosphorylase -> DPYD -> DPYS -> UPB1)

Pyrimidine nucleotides are degraded through a sequence of dephosphorylation, deamination and phosphorolysis that liberates the free bases uracil and thymine, followed by the three-step reductive ring-opening pathway that converts them to beta-alanine and beta-aminoisobutyrate. Pyrimidine mononucleotides (UMP, CMP) are dephosphorylated to uridine and cytidine by the erythrocyte-enriched cytosolic pyrimidine 5'-nucleotidase NT5C3A. Cytidine (and 2'-deoxycytidine) is deaminated to uridine (2'-deoxyuridine) by cytidine deaminase CDA. Uridine is phosphorolysed to uracil plus ribose-1-phosphate by uridine phosphorylase UPP1 (ubiquitous) or UPP2 (tissue-restricted paralog); thymidine is analogously phosphorolysed to thymine by thymidine phosphorylase TYMP. The liberated uracil and thymine then enter the conserved reductive catabolic pathway: dihydropyrimidine dehydrogenase DPYD reduces them (NADPH) to dihydrouracil/dihydrothymine, dihydropyrimidinase DPYS hydrolyses the ring to N-carbamyl-beta-alanine / N-carbamyl-beta-aminoisobutyrate, and beta-ureidopropionase UPB1 releases beta-alanine / beta-aminoisobutyrate (+ CO2 + NH3). This pathway also governs the activation and inactivation of pyrimidine-analog drugs: NT5C3A/CDA/UPP1/TYMP shape the fluoropyrimidine (5-FU, capecitabine) and cytidine-analog (gemcitabine, cytarabine) response, and DPYD loss-of-function causes severe 5-fluorouracil toxicity. Other deficiencies cause pyrimidine-5'-nucleotidase hemolytic anemia (NT5C3A), MNGIE (TYMP), and dihydropyrimidinuria (DPYD/DPYS/UPB1).

MODULE:pyrimidine_nucleotide_catabolismDRAFTMetabolic Pathwaymodules/pyrimidine_nucleotide_catabolism.yaml
pyrimidine nucleotide catabolic processGO:0006244 uracil catabolic processGO:0006212 beta-alanine biosynthetic processGO:0019483
GO:0006244
pyrimidine nucleotide catabolic process
NT5C3A/CDA/UPP1/UPP2/TYMP degrade pyrimidine nucleotides/nucleosides to free bases (GO:0006244).
GO:0006212
uracil catabolic process
DPYD/DPYS/UPB1 reductively degrade uracil to beta-alanine (GO:0006212).
GO:0019483
beta-alanine biosynthetic process
The reductive branch produces beta-alanine as its end product (GO:0019483).
file:human/NT5C3A/NT5C3A-ai-review.yaml
NT5C3A gene review (human)
Pyrimidine 5'-nucleotidase (UniProtKB:Q9H0P0, GO:0008253) matches the completed human NT5C3A review.
file:human/CDA/CDA-ai-review.yaml
CDA gene review (human)
Cytidine deaminase (UniProtKB:P32320, GO:0004126) matches the completed human CDA review.
file:human/UPP1/UPP1-ai-review.yaml
UPP1 gene review (human)
Uridine phosphorylase 1 (UniProtKB:Q16831, GO:0004850) matches the completed human UPP1 review.
file:human/UPP2/UPP2-ai-review.yaml
UPP2 gene review (human)
Uridine phosphorylase 2 (UniProtKB:O95045, GO:0004850) matches the completed human UPP2 review.
file:human/TYMP/TYMP-ai-review.yaml
TYMP gene review (human)
Thymidine phosphorylase (UniProtKB:P19971, GO:0009032) matches the completed human TYMP review.
file:human/DPYD/DPYD-ai-review.yaml
DPYD gene review (human)
Dihydropyrimidine dehydrogenase (UniProtKB:Q12882, GO:0017113) matches the completed human DPYD review.
file:human/DPYS/DPYS-ai-review.yaml
DPYS gene review (human)
Dihydropyrimidinase (UniProtKB:Q14117, GO:0004157) matches the completed human DPYS review.
file:human/UPB1/UPB1-ai-review.yaml
UPB1 gene review (human)
beta-ureidopropionase (UniProtKB:Q9UBR1, GO:0003837) matches the completed human UPB1 review.
8Nodes
7Parts
0Variant Sets
0Variants
7Annotons
7Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:pyrimidine_nucleotide_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

8 gene-function check(s) reflected in core functions · 0 conflict(s) · 7 evidence or coverage gap(s) (15 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
nt5c3a_activity NT5C3A (human)
UniProtKB:Q9H0P0
Family Representative 		5'-nucleotidase activity
GO:0008253 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cda_activity CDA (human)
UniProtKB:P32320
Family Representative 		cytidine deaminase activity
GO:0004126 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
upp_activity UPP1 (human; ubiquitous)
UniProtKB:Q16831
Family Representative 		uridine phosphorylase activity
GO:0004850 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
upp_activity UPP2 (human; tissue-restricted)
UniProtKB:O95045
Family Representative 		uridine phosphorylase activity
GO:0004850 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tymp_activity TYMP (human)
UniProtKB:P19971
Family Representative 		thymidine phosphorylase activity
GO:0009032 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpyd_activity DPYD (human)
UniProtKB:Q12882
Family Representative 		dihydropyrimidine dehydrogenase (NADP+) activity
GO:0017113 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dpys_activity DPYS (human)
UniProtKB:Q14117
Family Representative 		dihydropyrimidinase activity
GO:0004157 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
upb1_activity UPB1 (human)
UniProtKB:Q9UBR1
Family Representative 		beta-ureidopropionase activity
GO:0003837 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nt5c3a_activity NT5C3 / pyrimidine 5'-nucleotidase family
PANTHER:PTHR13045
Family 		5'-nucleotidase activity
GO:0008253 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR13045.
cda_activity CDA / cytidine deaminase family
PANTHER:PTHR11644
Family 		cytidine deaminase activity
GO:0004126 		Family Scope Restricted
GO:0004126 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Cytidine deaminases (SF2: human CDA, S. cerevisiae CDD1, S. pombe pcd1, fly CG8353), as pyrimidine_salvage selects. SF28 is not characterized.
upp_activity UPP / uridine phosphorylase family
PANTHER:PTHR43691
Family 		uridine phosphorylase activity
GO:0004850 		Family Scope Restricted
GO:0004850 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Asserted by pyrimidine_salvage and pyrimidine_nucleotide_catabolism; accepted by UPP1 and UPP2.
tymp_activity TYMP / thymidine phosphorylase family
PANTHER:PTHR10515
Family 		thymidine phosphorylase activity
GO:0009032 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR10515.
dpyd_activity DPYD / dihydropyrimidine dehydrogenase family
PANTHER:PTHR43073
Family 		dihydropyrimidine dehydrogenase (NADP+) activity
GO:0017113 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0017113.
dpys_activity DPYS / dihydropyrimidinase (amidohydrolase) family
PANTHER:PTHR11647
Family 		dihydropyrimidinase activity
GO:0004157 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0004157.
upb1_activity UPB1 / beta-ureidopropionase (nitrilase) family
PANTHER:PTHR43674
Family 		beta-ureidopropionase activity
GO:0003837 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0003837.

Gene-review completeness (8/8 grounded genes reviewed)

8 complete review(s) · 0 with deep research · 0 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
CDA P32320 ✓ ✓ ✗
DPYD Q12882 ✓ ✓ ✗
DPYS Q14117 ✓ ✓ ✗
NT5C3A Q9H0P0 ✓ ✓ ✗
TYMP P19971 ✓ ✓ ✗
UPB1 Q9UBR1 ✓ ✓ ✗
UPP1 Q16831 ✓ ✓ ✗
UPP2 O95045 ✓ ✓ ✗

Details

Context
cytosolGO:0005829
Pyrimidine nucleotide catabolismMetabolic Pathwaypyrimidine_nucleotide_catabolism
pyrimidine nucleotide catabolic processGO:0006244 uracil catabolic processGO:0006212 beta-alanine biosynthetic processGO:0019483
Context
cytosolGO:0005829

Pyrimidine nucleotide catabolism (GO:0006244 -> GO:0006212 -> GO:0019483), grounded to nine completed human gene reviews (four new: NT5C3A/CDA/UPP1/UPP2; five already-merged cited as nodes: TYMP PTHR10515, DPYD PTHR43073, DPYS PTHR11647, UPB1 PTHR43674). Route: UMP/CMP -> uridine/cytidine (NT5C3A Q9H0P0 PTHR13045, GO:0008253); cytidine -> uridine (CDA P32320 PTHR11644, GO:0004126, Zn2+); uridine -> uracil + R1P (UPP1 Q16831 / UPP2 O95045 PTHR43691, GO:0004850); thymidine -> thymine (TYMP P19971, GO:0009032); then the conserved reductive branch uracil/thymine -> dihydro (DPYD Q12882, GO:0017113, NADPH) -> N-carbamyl-beta- amino acids (DPYS Q14117, GO:0004157) -> beta-alanine/beta-aminoisobutyrate (UPB1 Q9UBR1, GO:0003837). All cytosolic. Curation notes from the new reviews: NT5C3A's two GO:0000215 tRNA-2'-phosphotransferase annotations are legacy mis-mappings (it is a pyrimidine 5'-nucleotidase, not the tRNA-splicing enzyme) -> flagged; CDA's direct substrates are the nucleosides not CMP/dCMP (monophosphate BP terms demoted); obsolete GO:0009972 "cytidine deamination" avoided; UPP2's vimentin/intermediate-filament IDA traces to a UPP1 paper predating UPP2 cloning (paralog mis-attribution, flagged MISCITED). This pathway also drives fluoropyrimidine (5-FU/capecitabine) and cytidine-analog (gemcitabine/cytarabine) drug metabolism; DPYD LOF -> 5-FU toxicity, NT5C3A -> hemolytic anemia, TYMP -> MNGIE, DPYD/DPYS/UPB1 -> dihydropyrimidinuria. GO term ids/labels verified against the local go.db; module passes structural + term-label validation.

Connections

pyrimidine_5nt -> cytidine_deamination Provides Input For
NT5C3A-made cytidine is deaminated by CDA.
pyrimidine_5nt -> uridine_phosphorolysis Provides Input For
NT5C3A-made uridine is phosphorolysed by UPP1/UPP2.
CDA-made uridine is phosphorolysed by UPP1/UPP2.
UPP-liberated uracil enters reductive catabolism at DPYD.
TYMP-liberated thymine enters reductive catabolism at DPYD.
DPYD-made dihydrouracil/dihydrothymine is hydrolysed by DPYS.
DPYS-made N-carbamyl-beta-amino acids are cleaved by UPB1.
Part 1: pyrimidine mononucleotide dephosphorylation (UMP/CMP -> uridine/cytidine)
Pyrimidine 5'-nucleotidase (NT5C3A)Reactionpyrimidine_5nt

Annotons

NT5C3A: pyrimidine 5'-nucleotidase
nt5c3a_activity
Participant: Family: NT5C3 / pyrimidine 5'-nucleotidase family
Family:
NT5C3 / pyrimidine 5'-nucleotidase familyPANTHER:PTHR13045
Representative Members: NT5C3A (human)UniProtKB:Q9H0P0

Function

5'-nucleotidase activityGO:0008253
Substrates: UMP / CMP (Mg2+)
Products: uridine / cytidine phosphate

Locations

cytosolGO:0005829

Dephosphorylate UMP/CMP to uridine/cytidine.

Part 2: cytidine deamination (cytidine -> uridine)
Cytidine deaminase (CDA)Reactioncytidine_deamination

Annotons

CDA: cytidine deaminase
cda_activity
Participant: Family: CDA / cytidine deaminase family
Family:
CDA / cytidine deaminase familyPANTHER:PTHR11644
Representative Members: CDA (human)UniProtKB:P32320

Function

cytidine deaminase activityGO:0004126
Substrates: cytidine / 2'-deoxycytidine (Zn2+)
Products: uridine / 2'-deoxyuridine ammonia

Locations

cytosolGO:0005829

Deaminate cytidine to uridine.

Part 3: uridine phosphorolysis (uridine -> uracil + ribose-1-P)
Uridine phosphorylase (UPP1 / UPP2)Reactionuridine_phosphorolysis

Annotons

UPP1/UPP2: uridine phosphorylase
upp_activity
Participant: Family: UPP / uridine phosphorylase family
Family:
UPP / uridine phosphorylase familyPANTHER:PTHR43691
Representative Members: UPP1 (human; ubiquitous)UniProtKB:Q16831 UPP2 (human; tissue-restricted)UniProtKB:O95045

Function

uridine phosphorylase activityGO:0004850
Substrates: uridine / 2'-deoxyuridine phosphate
Products: uracil (2-deoxy)ribose 1-phosphate

Locations

cytosolGO:0005829

Phosphorolyse uridine to uracil + ribose-1-phosphate.

Part 4: thymidine phosphorolysis (thymidine -> thymine)
Thymidine phosphorylase (TYMP)Reactionthymidine_phosphorolysis

Annotons

TYMP: thymidine phosphorylase
tymp_activity
Participant: Family: TYMP / thymidine phosphorylase family
Family:
TYMP / thymidine phosphorylase familyPANTHER:PTHR10515
Representative Members: TYMP (human)UniProtKB:P19971

Function

thymidine phosphorylase activityGO:0009032
Substrates: thymidine / 2'-deoxyuridine phosphate
Products: thymine / uracil 2-deoxyribose 1-phosphate

Locations

cytosolGO:0005829

Phosphorolyse thymidine to thymine + deoxyribose-1-phosphate.

Part 5: dihydropyrimidine reduction (uracil/thymine -> dihydro)
Dihydropyrimidine dehydrogenase (DPYD)Reactiondihydropyrimidine_reduction

Annotons

DPYD: dihydropyrimidine dehydrogenase
dpyd_activity
Participant: Family: DPYD / dihydropyrimidine dehydrogenase family
Family:
DPYD / dihydropyrimidine dehydrogenase familyPANTHER:PTHR43073
Representative Members: DPYD (human)UniProtKB:Q12882

Function

dihydropyrimidine dehydrogenase (NADP+) activityGO:0017113
Substrates: uracil / thymine NADPH
Products: 5,6-dihydrouracil / 5,6-dihydrothymine

Locations

cytosolGO:0005829

Reduce uracil/thymine to dihydrouracil/dihydrothymine.

Part 6: dihydropyrimidine ring hydrolysis
Dihydropyrimidinase (DPYS)Reactiondihydropyrimidine_hydrolysis

Annotons

DPYS: dihydropyrimidinase
dpys_activity
Participant: Family: DPYS / dihydropyrimidinase (amidohydrolase) family
Family:
DPYS / dihydropyrimidinase (amidohydrolase) familyPANTHER:PTHR11647
Representative Members: DPYS (human)UniProtKB:Q14117

Function

dihydropyrimidinase activityGO:0004157
Substrates: 5,6-dihydrouracil / 5,6-dihydrothymine H2O
Products: N-carbamoyl-beta-alanine / N-carbamoyl-beta-aminoisobutyrate

Locations

cytosolGO:0005829

Hydrolyse the dihydropyrimidine ring to N-carbamyl-beta-amino acids.

Part 7: ureido hydrolysis (-> beta-alanine)
beta-ureidopropionase (UPB1)Reactionureidopropionase

Annotons

UPB1: beta-ureidopropionase
upb1_activity
Participant: Family: UPB1 / beta-ureidopropionase (nitrilase) family
Family:
UPB1 / beta-ureidopropionase (nitrilase) familyPANTHER:PTHR43674
Representative Members: UPB1 (human)UniProtKB:Q9UBR1

Function

beta-ureidopropionase activityGO:0003837
Substrates: N-carbamoyl-beta-alanine / N-carbamoyl-beta-aminoisobutyrate H2O
Products: beta-alanine / beta-aminoisobutyrate CO2 + ammonia

Locations

cytosolGO:0005829

Release beta-alanine/beta-aminoisobutyrate (+ CO2 + NH3).