Galactose catabolism (Leloir pathway)

The four-reaction Leloir pathway converts D-galactose to glucose 1-phosphate. Aldose 1-epimerase supplies alpha-D-galactose, galactokinase forms galactose 1-phosphate, galactose-1-phosphate uridylyltransferase exchanges UMP with UDP-glucose, and UDP-glucose 4-epimerase regenerates UDP-glucose from UDP-galactose. The pathway is catalytic in its UDP-sugar co-substrate and is distinct from nucleotide-sugar biosynthesis or isolated UDP-galactose epimerization in organisms that lack the upstream GalK/GalT reactions.

MODULE:galactose_leloir_pathwayDRAFTMetabolic Pathwaymodules/galactose_leloir_pathway.yaml
beta-D-galactose catabolic process via UDP-galactose, Leloir pathwayGO:0033499 galactose metabolic processGO:0006012
GO:0006012
galactose metabolic process
The module is grounded in the GO galactose metabolic/catabolic process terms (GO:0006012, GO:0019388, and the Leloir-specific GO:0033499); every step is annotated within them.
Reactome:R-HSA-70370
Galactose catabolism
Step order and reaction stoichiometries follow the human Reactome "Galactose catabolism" pathway (R-HSA-70370) and its member reactions (R-HSA-9931853, R-HSA-70355, R-HSA-70361, R-HSA-70369).
file:human/GALM/GALM-ai-review.yaml
GALM gene review (human)
The GALM step grounding (UniProtKB:Q96C23, GO:0004034 aldose 1-epimerase activity) matches the completed human GALM review.
file:human/GALK1/GALK1-ai-review.yaml
GALK1 gene review (human)
The GALK1 step grounding (UniProtKB:P51570, GO:0004335 galactokinase activity, EC 2.7.1.6) matches the completed human GALK1 review.
file:human/GALT/GALT-ai-review.yaml
GALT gene review (human)
The GALT step grounding (UniProtKB:P07902, GO:0008108 UDP-glucose:hexose-1-phosphate uridylyltransferase activity, EC 2.7.7.12) matches the completed human GALT review.
file:human/GALE/GALE-ai-review.yaml
GALE gene review (human)
The GALE step grounding (UniProtKB:Q14376, GO:0003978 UDP-glucose 4-epimerase activity, EC 5.1.3.2) matches the completed human GALE review.
file:interpro/panther/panther-members.tsv
Curated UniProt-to-PANTHER membership index
The local index verifies the bacterial and human representative members against the declared GalM, GalK, GalT, and GalE PANTHER families.
file:projects/P_PUTIDA/deep-research/PSEPK__galactose_leloir_pathway__ppu00052-deep-research-openscientist.md
PSEPK Leloir module/pathway/taxon deep research
OpenScientist research found no identifiable GalK or GalT in KT2440 and independently classified the focused catabolic Leloir route as unsatisfiable; PP_1165 remained substrate-uncertain and GalE alone did not establish catabolic pathway coverage.
5Nodes
4Parts
0Variant Sets
0Variants
4Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:galactose_leloir_pathway 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.

Gene-review completeness (5/9 grounded genes reviewed)

5 complete review(s) · 2 with deep research · 4 missing review · 3 reviewed but lacking deep research

Gene Review Complete Deep research
GALE Q14376 ✓ ✓ ✗
galE Q88I72 ✓ ✓ ✓
GALK1 P51570 ✓ ✓ ✗
GALM Q96C23 ✓ ✓ ✗
GALT P07902 ✓ ✓ ✓
GalE (Escherichia coli K-12) P09147 ✗ — —
GalT (Escherichia coli K-12) P09148 ✗ — —
GalK (Escherichia coli K-12) P0A6T3 ✗ — —
GalM (Escherichia coli K-12) P0A9C3 ✗ — —

Details

Galactose catabolism (Leloir pathway)Metabolic Pathwaygalactose_leloir_pathway
beta-D-galactose catabolic process via UDP-galactose, Leloir pathwayGO:0033499 galactose metabolic processGO:0006012

Four-reaction Leloir pathway grounded with reviewed bacterial and human exemplars, exact reactions, and locally verified PAINT nodes. PSEPK GalE Q88I72 is included as a concrete epimerase exemplar, but an isolated GalE does not satisfy the module without GalK and GalT.

Connections

galm_step -> galk1_step Provides Input For
alpha-D-galactose from GALM is the substrate phosphorylated by GALK1.
galk1_step -> galt_step Provides Input For
alpha-D-galactose 1-phosphate from GALK1 is the substrate of GALT.
galt_step -> gale_step Provides Input For
UDP-galactose produced by GALT is epimerised by GALE to UDP-glucose.
gale_step -> galt_step Provides Input For
UDP-glucose regenerated by GALE is the co-substrate GALT requires, closing the UDP-sugar recycling loop that makes the pathway catalytic in UDP-glucose.
Part 1: anomer preparation (mutarotation)
beta-D-galactose to alpha-D-galactoseReactiongalm_step

Annotons

GALM: galactose mutarotase / aldose 1-epimerase
galm_activity
Participant: Family: Galactose mutarotase subfamily (GALM)
Family:
Galactose mutarotase subfamily (GALM)PANTHER:PTHR10091:SF0 Reviewed E. coli and human GalM proteins share the exact galactose-mutarotase subfamily. The unresolved PSEPK aldose 1-epimerase candidate is not used as a specificity exemplar.
Representative Members: GalM (Escherichia coli K-12)UniProtKB:P0A9C3 GALM (human)UniProtKB:Q96C23

Function

aldose 1-epimerase activityGO:0004034
Substrates: beta-D-galactose
Products: alpha-D-galactose

Accelerates the anomeric equilibration of D-galactose to supply the alpha-anomer required by galactokinase.

Part 2: phosphorylation (committed step)
alpha-D-galactose + ATP to alpha-D-galactose 1-phosphate + ADPReactiongalk1_step

Annotons

GALK1: galactokinase
galk1_activity
Participant: Family: Galactokinase subfamily (GalK/GALK1)
Family:
Galactokinase subfamily (GalK/GALK1)PANTHER:PTHR10457:SF7 The reviewed bacterial and human galactokinases both resolve to PTHR10457:SF7; the official historical label is retained.
Representative Members: GalK (Escherichia coli K-12)UniProtKB:P0A6T3 GALK1 (human)UniProtKB:P51570

Function

galactokinase activityGO:0004335
Substrates: alpha-D-galactose ATP
Products: alpha-D-galactose 1-phosphate ADP

First committed step: ATP-dependent phosphorylation of galactose to galactose 1-phosphate.

Part 3: uridylyl transfer (central step)
alpha-D-galactose 1-phosphate + UDP-glucose to glucose-1-phosphate + UDP-galactoseReactiongalt_step

Annotons

GALT: galactose-1-phosphate uridylyltransferase
galt_activity
Participant: Family: Galactose-1-phosphate uridylyltransferase subfamily (GalT/GALT)
Family:
Galactose-1-phosphate uridylyltransferase subfamily (GalT/GALT)PANTHER:PTHR11943:SF1
Representative Members: GalT (Escherichia coli K-12)UniProtKB:P09148 GALT (human)UniProtKB:P07902

Function

UDP-glucose:hexose-1-phosphate uridylyltransferase activityGO:0008108
Substrates: alpha-D-galactose 1-phosphate UDP-glucose
Products: glucose-1-phosphate UDP-galactose

Converts galactose 1-phosphate to glucose 1-phosphate while producing UDP-galactose for the epimerase reaction.

Part 4: UDP-sugar recycling (regenerates UDP-glucose for GALT)
UDP-galactose to UDP-glucose (reversible)Reactiongale_step

Annotons

GALE: UDP-galactose-4-epimerase
gale_activity
Participant: Family: UDP-glucose 4-epimerase family (GALE)
Family:
UDP-glucose 4-epimerase family (GALE)PANTHER:PTHR43725 E. coli and human GalE resolve to SF47, whereas PSEPK GalE is currently classified in heterogeneous SF53. The verified parent family, exact reaction, and protein records preserve cross-species coverage without a false subfamily claim.
Representative Members: GalE (Escherichia coli K-12)UniProtKB:P09147 GALE (human)UniProtKB:Q14376 GalE (Pseudomonas putida KT2440)UniProtKB:Q88I72

Function

UDP-glucose 4-epimerase activityGO:0003978
Substrates: UDP-galactose NAD+ (tightly bound cofactor)
Products: UDP-glucose

NAD+-dependent epimerization that regenerates the UDP-glucose consumed by GALT. UDP-glucose 4-epimerases also serve nucleotide- sugar biosynthesis outside Leloir catabolism.