UDP-glucose and UDP-galactose biosynthesis

Bacterial module for de novo production of UDP-glucose from the central glucose 6-phosphate pool and its reversible interconversion with UDP-galactose. Three reactions make up the module: phosphoglucomutase isomerizes glucose 6-phosphate to alpha-D-glucose 1-phosphate, UTP--glucose-1-phosphate uridylyltransferase (GalU) activates glucose 1-phosphate as UDP-glucose, and NAD-dependent UDP-glucose 4-epimerase (GalE) interconverts UDP-glucose and UDP-galactose. The phosphoglucomutase step is supplied by non-homologous or distantly related enzyme families that differ between lineages: a PGM1-type phosphoglucomutase (Escherichia coli Pgm), a PGM2-type phosphoglucomutase (Bacillus subtilis PgcA), or a bifunctional phosphomannomutase/phosphoglucomutase (Pseudomonas aeruginosa AlgC). The activated hexoses feed lipopolysaccharide core, teichoic acid and glycolipid anchors, capsular and exopolysaccharides, trehalose and other glycoconjugates; those consuming pathways, and galactose uptake and catabolism, are outside this module.

MODULE:udp_glucose_and_udp_galactose_biosynthesisCOMPLETECONCRETEMetabolic Pathwaymodules/udp_glucose_and_udp_galactose_biosynthesis.yaml
UDP-alpha-D-glucose biosynthetic processGO:0120530 UDP-galactose biosynthetic processGO:0052574
PMID:7961613
Overproduction and characterization of recombinant UDP-glucose pyrophosphorylase from Escherichia coli K-12.
Recombinant E. coli GalU purified to homogeneity catalyzes Mg2+-dependent synthesis and pyrophosphorolysis of UDP-glucose, and the cloned gene complements a galU mutant; the prokaryotic enzyme is structurally unrelated to eukaryotic UDP-glucose pyrophosphorylases.
PMID:14216423
Purified E. coli phosphoglucomutase interconverts glucose 1-phosphate and glucose 6-phosphate (Mg2+-dependent; UniProt P36938 catalytic activity evidence).
PMID:14235524
E. coli UDP-galactose 4-epimerase interconverts UDP-galactose and UDP-glucose and is specific for these two nucleotide sugars (UniProt P09147 function evidence).
PMID:8050998
P. aeruginosa AlgC is a bifunctional enzyme with both phosphomannomutase and phosphoglucomutase activities (UniProt P26276 catalytic activity evidence).
PMID:15640167
B. subtilis PgcA interconverts glucose 6-phosphate and glucose 1-phosphate as the first step of glucolipid and UDP-glucose-dependent envelope polymer synthesis (UniProt P18159 function evidence).
file:PSEPK/galU/galU-uniprot.txt
UniProtKB entry for Pseudomonas putida KT2440 galU
P. putida KT2440 Q88GA4 carries the UDPGP type 2 (GalU) family signature and the RHEA:19889 reaction, and is retained as a Pseudomonas exemplar alongside the E. coli enzymes.

Taxonomic scope. The three reactions are conserved across Bacteria, so the module is written species-neutrally with E. coli K-12 (Pgm, GalU, GalE), B. subtilis 168 (PgcA) and P. aeruginosa PAO1 (AlgC) as experimentally characterized exemplars and P. putida KT2440 (Pgm/PP_3578, AlgC/PP_5288, GalU/PP_3821, GalE/PP_3129) kept as a homology-grounded exemplar. The module is scoped to Bacteria rather than all life because the UDP-glucose pyrophosphorylase step is family-specific: bacterial GalU belongs to the prokaryotic UDPGP type 2 family (PANTHER PTHR43197), whereas eukaryotic UGP1/UGP2 belong to a structurally distinct UDPGP type 1 family; the eukaryotic route is better modelled separately. Phosphoglucomutase family choice. E. coli Pgm (PTHR22573:SF57) and B. subtilis PgcA / P. putida Pgm (PTHR45745:SF1) are both dedicated phosphoglucomutases but sit in different PANTHER families of the alpha-D-phosphohexomutase superfamily, so they are modelled as separate variants rather than one family descriptor. The bifunctional AlgC-type route (PTHR43771:SF2) can coexist with a dedicated Pgm; in P. aeruginosa AlgC supplies glucose 1-phosphate for LPS core synthesis, while in P. putida the in-vivo flux split between Pgm and AlgC has not been measured. P. putida CpsG/PP_1777 is excluded because current evidence supports phosphomannomutase rather than phosphoglucomutase activity. GalE grounding. The epimerase is grounded on two PTHR43725 subfamilies: E. coli GalE is in SF47 and P. putida GalE in SF53. SF53's PANTHER name (UDP-ARABINOSE 4-EPIMERASE 1) does not describe the bacterial members, which are UDP-glucose 4-epimerases; a single-subfamily grounding would exclude one exemplar, and the whole-family id would also cover the plant UDP-arabinose 4-epimerase subfamilies (SF33, SF38) to which the activity does not apply. Out of scope. Glucose kinase, aldose mutarotation, galactose uptake and Leloir catabolism (modules/galactose_leloir_pathway.yaml), glycogen synthesis, and downstream polymer assembly are separate modules.

7Nodes
3Parts
1Variant Sets
3Variants
5Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • udp_glucose_and_udp_galactose_biosynthesis-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.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • phosphoglucomutase_step → galu_udp_glucose_step [NOT_CHECKED]
  • galu_udp_glucose_step → gale_udp_glucose_epimerase_step [NOT_CHECKED]

Function consistency and core coverage

9 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 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
pgm1_type_phosphoglucomutase pgm (Escherichia coli K-12)
UniProtKB:P36938
Family Representative 		phosphoglucomutase activity
GO:0004614 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pgm2_type_phosphoglucomutase pgcA (Bacillus subtilis 168)
UniProtKB:P18159
Family Representative 		phosphoglucomutase activity
GO:0004614 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pgm2_type_phosphoglucomutase pgm (Pseudomonas putida KT2440)
UniProtKB:Q88GY7
Family Representative 		phosphoglucomutase activity
GO:0004614 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
algc_phosphoglucomutase algC (Pseudomonas aeruginosa PAO1)
UniProtKB:P26276
Family Representative 		phosphoglucomutase activity
GO:0004614 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
algc_phosphoglucomutase algC (Pseudomonas putida KT2440)
UniProtKB:Q88C93
Family Representative 		phosphoglucomutase activity
GO:0004614 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
galu_uridylyltransferase galU (Escherichia coli K-12)
UniProtKB:P0AEP3
Family Representative 		UTP:glucose-1-phosphate uridylyltransferase activity
GO:0003983 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
galu_uridylyltransferase galU (Pseudomonas putida KT2440)
UniProtKB:Q88GA4
Family Representative 		UTP:glucose-1-phosphate uridylyltransferase activity
GO:0003983 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gale_udp_glucose_4_epimerase galE (Escherichia coli K-12)
UniProtKB:P09147
Family Representative 		UDP-glucose 4-epimerase activity
GO:0003978 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gale_udp_glucose_4_epimerase galE (Pseudomonas putida KT2440)
UniProtKB:Q88I72
Family Representative 		UDP-glucose 4-epimerase activity
GO:0003978 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pgm1_type_phosphoglucomutase bacterial PGM1-type phosphoglucomutase subfamily
PANTHER:PTHR22573:SF57
Family 		phosphoglucomutase activity
GO:0004614 		Family Supported
Family review supports GO:0004614 FAMILY_WIDE. This is the defining activity of the bacterial, fungal, animal and plant PGMs. The five modules that use this family assert it with catalytic representatives (yeast PGM1/PGM2, S. pombe SPBC32F12.10, human PGM1): dolichol_phosphate_sugar_donor_supply, emp_glycolysis, galactose_leloir_pathway, glycogenolysis, and glycogen_metabolism_fungal (as SF2). The vertebrate PGM5 clade (SF27) is the exception, and PAINT already excludes it with an IKR.
pgm2_type_phosphoglucomutase bacterial PGM2-type phosphoglucomutase subfamily
PANTHER:PTHR45745:SF1
Family 		phosphoglucomutase activity
GO:0004614 		Family Supported
Family review supports GO:0004614 for PANTHER:PTHR45745:SF1. The established physiological activity of the bacterial SF1 members (B. subtilis PgcA, by mutant enzyme assays and genetics), asserted for SF1 by the udp_glucose_and_udp_galactose_biosynthesis module with B. subtilis PgcA and P. putida Pgm. Vertebrate PGM2 (SF3) retains weaker phosphoglucomutase activity and PGM2L1 (SF2) little; yeast Pgm3 in SF1 is mainly a phosphoribomutase. PAINT places no phosphoglucomutase IBD in this family.
algc_phosphoglucomutase bifunctional phosphomannomutase/phosphoglucomutase subfamily
PANTHER:PTHR43771:SF2
Family 		phosphoglucomutase activity
GO:0004614 		Family Supported
Family review supports GO:0004614 for PANTHER:PTHR43771:SF2. Shown biochemically and genetically for the SF2 archetype P. aeruginosa AlgC (purified enzyme; PGM activity lost in algC mutants), and asserted for SF2 members by the udp_glucose_and_udp_galactose_biosynthesis module (P. aeruginosa and P. putida AlgC). PAINT places no phosphoglucomutase IBD in this family, and SF1 members are not established here as phosphoglucomutases.
galu_uridylyltransferase bacterial UTP--glucose-1-phosphate uridylyltransferase (GalU) subfamily
PANTHER:PTHR43197:SF1
Family 		UTP:glucose-1-phosphate uridylyltransferase activity
GO:0003983 		Family Supported
Family review supports GO:0003983 FAMILY_WIDE. The defining activity of the family, seeded across Gram-negative and Gram-positive bacteria. Asserted by the udp_glucose_and_udp_galactose_biosynthesis module with E. coli GalU and P. putida GalU (SF1). GalF (SF2) has only residual activity but is not catalytically dead.
gale_udp_glucose_4_epimerase bacterial GalE UDP-glucose 4-epimerase subfamilies of PTHR43725
PANTHER:PTHR43725:SF47
Family 		UDP-glucose 4-epimerase activity
GO:0003978 		Family Supported
Family review supports GO:0003978 for PANTHER:PTHR43725:SF47. Asserted by galactose_leloir_pathway (on SF47, with E. coli GalE, human GALE and the yeast GAL10/gal10 epimerase domains) and by udp_glucose_and_udp_galactose_biosynthesis (on SF47 and SF53, with E. coli and P. putida GalE); accepted by GALE, GAL10, gal10, E. coli galE and P. putida galE. The plant UDP-arabinose 4-epimerase subfamilies (SF33, SF38) and the CSP41 subfamilies (SF6, SF8) are excluded.
gale_udp_glucose_4_epimerase bacterial GalE UDP-glucose 4-epimerase subfamilies of PTHR43725
PANTHER:PTHR43725:SF53
Family 		UDP-glucose 4-epimerase activity
GO:0003978 		Family Supported
Family review supports GO:0003978 for PANTHER:PTHR43725:SF53. Asserted by galactose_leloir_pathway (on SF47, with E. coli GalE, human GALE and the yeast GAL10/gal10 epimerase domains) and by udp_glucose_and_udp_galactose_biosynthesis (on SF47 and SF53, with E. coli and P. putida GalE); accepted by GALE, GAL10, gal10, E. coli galE and P. putida galE. The plant UDP-arabinose 4-epimerase subfamilies (SF33, SF38) and the CSP41 subfamilies (SF6, SF8) are excluded.

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

9 complete review(s) · 4 with deep research · 0 missing review · 5 reviewed but lacking deep research

Gene Review Complete Deep research
algC P26276 ✓ ✓ ✗
algC Q88C93 ✓ ✓ ✓
galE P09147 ✓ ✓ ✗
galE Q88I72 ✓ ✓ ✓
galU P0AEP3 ✓ ✓ ✗
galU Q88GA4 ✓ ✓ ✓
pgcA P18159 ✓ ✓ ✗
pgm P36938 ✓ ✓ ✗
pgm Q88GY7 ✓ ✓ ✓

Details

Context
bacteriaNCBITaxon:2
UDP-glucose and UDP-galactose biosynthesisMetabolic Pathwayudp_glucose_and_udp_galactose_biosynthesis

Glucose 6-phosphate to glucose 1-phosphate to UDP-glucose, with reversible epimerization of UDP-glucose to UDP-galactose.

UDP-alpha-D-glucose biosynthetic processGO:0120530 UDP-galactose biosynthetic processGO:0052574
Context
bacteriaNCBITaxon:2

Connections

Glucose 1-phosphate made by phosphoglucomutase is the GalU substrate.
UDP-glucose made by GalU is the GalE substrate for UDP-galactose formation.
Part 1: glucose 1-phosphate formation
Phosphoglucomutase reactionReactionphosphoglucomutase_step

Alternative enzyme solutions supply this reaction. A dedicated PGM1-type or PGM2-type phosphoglucomutase, or a bifunctional AlgC-type phosphomannomutase/phosphoglucomutase, may provide glucose 1-phosphate; an organism needs at least one and may carry several.

Variant set: Glucose 1-phosphate enzyme route by phosphoglucomutase enzyme family (One Or More)
Dedicated PGM1-type phosphoglucomutase routeReactionpgm1_type_pgm_variant

Annotons

Pgm (PGM1-type): phosphoglucomutase
pgm1_type_phosphoglucomutase
Participant: Family: bacterial PGM1-type phosphoglucomutase subfamily
Family:
bacterial PGM1-type phosphoglucomutase subfamilyPANTHER:PTHR22573:SF57
Representative Members: pgm (Escherichia coli K-12)UniProtKB:P36938

Function

phosphoglucomutase activityGO:0004614
Substrates: alpha-D-glucose 6-phosphate
Products: alpha-D-glucose 1-phosphate
Cofactors: Mg2+

Processes

UDP-alpha-D-glucose biosynthetic processGO:0120530

Provides glucose 1-phosphate from the central glucose 6-phosphate pool.

Dedicated PGM2-type phosphoglucomutase routeReactionpgm2_type_pgm_variant

Annotons

PgcA/Pgm (PGM2-type): phosphoglucomutase
pgm2_type_phosphoglucomutase
Participant: Family: bacterial PGM2-type phosphoglucomutase subfamily
Family:
bacterial PGM2-type phosphoglucomutase subfamilyPANTHER:PTHR45745:SF1
Representative Members: pgcA (Bacillus subtilis 168)UniProtKB:P18159 pgm (Pseudomonas putida KT2440)UniProtKB:Q88GY7

Function

phosphoglucomutase activityGO:0004614
Substrates: alpha-D-glucose 6-phosphate
Products: alpha-D-glucose 1-phosphate
Cofactors: Mg2+

Processes

UDP-alpha-D-glucose biosynthetic processGO:0120530

Provides glucose 1-phosphate from the central glucose 6-phosphate pool in lineages that use a PGM2-type enzyme.

Bifunctional AlgC routeReactionbifunctional_algc_variant

Annotons

AlgC: phosphoglucomutase
algc_phosphoglucomutase
Participant: Family: bifunctional phosphomannomutase/phosphoglucomutase subfamily
Family:
bifunctional phosphomannomutase/phosphoglucomutase subfamilyPANTHER:PTHR43771:SF2
Representative Members: algC (Pseudomonas aeruginosa PAO1)UniProtKB:P26276 algC (Pseudomonas putida KT2440)UniProtKB:Q88C93

Function

phosphoglucomutase activityGO:0004614
Substrates: alpha-D-glucose 6-phosphate
Products: alpha-D-glucose 1-phosphate
Cofactors: Mg2+

Processes

UDP-alpha-D-glucose biosynthetic processGO:0120530

Provides glucose 1-phosphate through a bifunctional enzyme that also supplies mannose 1-phosphate for GDP-mannose; in P. aeruginosa this activity feeds LPS core synthesis.

Part 2: UDP-glucose formation
UTP--glucose-1-phosphate uridylyltransferase reactionReactiongalu_udp_glucose_step

Annotons

GalU: UTP--glucose-1-phosphate uridylyltransferase
galu_uridylyltransferase
Participant: Family: bacterial UTP--glucose-1-phosphate uridylyltransferase (GalU) subfamily
Family:
bacterial UTP--glucose-1-phosphate uridylyltransferase (GalU) subfamilyPANTHER:PTHR43197:SF1
Representative Members: galU (Escherichia coli K-12)UniProtKB:P0AEP3 galU (Pseudomonas putida KT2440)UniProtKB:Q88GA4

Function

UTP:glucose-1-phosphate uridylyltransferase activityGO:0003983
Substrates: UTP alpha-D-glucose 1-phosphate
Products: UDP-alpha-D-glucose diphosphate
Cofactors: Mg2+

Processes

UDP-alpha-D-glucose biosynthetic processGO:0120530

Activates glucose 1-phosphate as UDP-glucose.

Part 3: UDP-galactose formation and interconversion
UDP-glucose 4-epimerase reactionReactiongale_udp_glucose_epimerase_step

Annotons

GalE: UDP-glucose 4-epimerase
gale_udp_glucose_4_epimerase
Participant: Family: bacterial GalE UDP-glucose 4-epimerase subfamilies of PTHR43725
Family:
bacterial GalE UDP-glucose 4-epimerase subfamilies of PTHR43725
Representative Members: galE (Escherichia coli K-12)UniProtKB:P09147 galE (Pseudomonas putida KT2440)UniProtKB:Q88I72

Function

UDP-glucose 4-epimerase activityGO:0003978
Substrates: UDP-alpha-D-glucose
Products: UDP-alpha-D-galactose
Cofactors: NAD+

Processes

UDP-galactose biosynthetic processGO:0052574

Reversibly interconverts UDP-glucose and UDP-galactose to supply both activated hexose pools.