Entner-Doudoroff glycolysis and gluconeogenesis module

A taxon-neutral module for bacterial hexose-phosphate central carbon metabolism in organisms that route glucose through the Entner-Doudoroff pathway rather than relying on a complete forward Embden-Meyerhof-Parnas glycolytic route. The module separates the upper Entner-Doudoroff branch from shared lower glycolytic reactions and from gluconeogenic bypass reactions that regenerate hexose phosphate from pyruvate, phosphoenolpyruvate, or triose phosphate precursors.

MODULE:entner_doudoroff_and_gluconeogenesisDRAFTMetabolic Pathwaymodules/entner_doudoroff_and_gluconeogenesis.yaml

glycolytic process via Entner-Doudoroff PathwayGO:0061678 gluconeogenesisGO:0006094

GO:0061678

Entner-Doudoroff pathway

GO:0061678 grounds both the module and its committed 6-phosphogluconate branch. The route-specific terms GO:0061688 (glycolytic process via Entner-Doudoroff Pathway) and GO:0009255 (Entner-Doudoroff pathway through 6-phosphogluconate) were obsoleted in GO release 2026-05-19 (replaced_by GO:0006096 and GO:0061678 respectively); the variant distinction is carried by the module structure rather than by the term.

GO:0006094

gluconeogenesis

The reverse/anabolic route from lower central-carbon intermediates to hexose phosphates is grounded in the gluconeogenesis process term.

file:modules/entner_doudoroff_and_gluconeogenesis-deep-research-falcon.md

Falcon module research for Entner-Doudoroff glycolysis and gluconeogenesis

Module-level research supports splitting ED-centered bacterial glucose catabolism from canonical EMP glycolysis and treating gluconeogenic bypasses as part of the same central-carbon module.

file:projects/P_PUTIDA/deep-research/PSEPK__entner_doudoroff_and_gluconeogenesis__ppu00010-deep-research-falcon.md

Falcon PSEPK ppu00010 pathway satisfiability review

PSEPK-specific pathway research found that KEGG ppu00010 includes only a subset of the KT2440 ED/gluconeogenesis candidates and that core ED genes must be pulled from the neighboring pentose-phosphate boundary.

25Nodes

20Parts

2Variant Sets

4Variants

17Annotons

4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

entner_doudoroff_and_gluconeogenesis-deep-research-falcon.md (falcon)

Leaf nodes lacking representative members

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

Glucose phosphorylation ANY_WITH_FUNCTION
Glucose 6-phosphate dehydrogenase ANY_WITH_FUNCTION
6-phosphogluconolactonase ANY_WITH_FUNCTION
6-phosphogluconate dehydratase ANY_WITH_FUNCTION
KDPG aldolase ANY_WITH_FUNCTION
Triose-phosphate isomerase ANY_WITH_FUNCTION
Glyceraldehyde-3-phosphate dehydrogenase ANY_WITH_FUNCTION
Phosphoglycerate kinase ANY_WITH_FUNCTION
Phosphoglycerate mutase ANY_WITH_FUNCTION
Enolase ANY_WITH_FUNCTION
Pyruvate kinase ANY_WITH_FUNCTION
Phosphoenolpyruvate synthase route ANY_WITH_FUNCTION
GTP-dependent PEP carboxykinase ANY_WITH_FUNCTION
ATP-dependent PEP carboxykinase ANY_WITH_FUNCTION
Fructose-bisphosphate aldolase ANY_WITH_FUNCTION
Fructose 1,6-bisphosphatase ANY_WITH_FUNCTION
Glucose-6-phosphate isomerase ANY_WITH_FUNCTION

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.

glucokinase_step → glucose_6_phosphate_to_6_phosphogluconate [NOT_CHECKED]
glucose_6_phosphate_to_6_phosphogluconate → entner_doudoroff_branch [NOT_CHECKED]
lower_emp_trunk → gluconeogenic_bypasses [NOT_CHECKED]

Function consistency and core coverage

0 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (17 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.

Annoton	Participant	Function	Assessment
glucokinase_activity	ANY_WITH_FUNCTION Gene	glucokinase activity GO:0004340	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
glucose_6_phosphate_dehydrogenase_activity	ANY_WITH_FUNCTION Gene	glucose-6-phosphate dehydrogenase activity GO:0004345	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
phosphogluconolactonase_activity	ANY_WITH_FUNCTION Gene	6-phosphogluconolactonase activity GO:0017057	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
phosphogluconate_dehydratase_activity	ANY_WITH_FUNCTION Gene	phosphogluconate dehydratase activity GO:0004456	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
kdpg_aldolase_activity	ANY_WITH_FUNCTION Gene	2-dehydro-3-deoxy-phosphogluconate aldolase activity GO:0008675	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
triose_phosphate_isomerase_activity	ANY_WITH_FUNCTION Gene	triose-phosphate isomerase activity GO:0004807	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
gapdh_activity	ANY_WITH_FUNCTION Gene	glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity GO:0004365	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
phosphoglycerate_kinase_activity	ANY_WITH_FUNCTION Gene	phosphoglycerate kinase activity GO:0004618	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
phosphoglycerate_mutase_activity	ANY_WITH_FUNCTION Gene	phosphoglycerate mutase activity GO:0004619	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
enolase_activity	ANY_WITH_FUNCTION Gene	phosphopyruvate hydratase activity GO:0004634	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
pyruvate_kinase_activity	ANY_WITH_FUNCTION Gene	pyruvate kinase activity GO:0004743	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
pep_synthase_activity	ANY_WITH_FUNCTION Gene	pyruvate, water dikinase activity GO:0008986	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
gtp_pepck_activity	ANY_WITH_FUNCTION Gene	phosphoenolpyruvate carboxykinase (GTP) activity GO:0004613	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
atp_pepck_activity	ANY_WITH_FUNCTION Gene	phosphoenolpyruvate carboxykinase (ATP) activity GO:0004612	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
fructose_bisphosphate_aldolase_activity	ANY_WITH_FUNCTION Gene	fructose-bisphosphate aldolase activity GO:0004332	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
fructose_bisphosphatase_activity	ANY_WITH_FUNCTION Gene	fructose 1,6-bisphosphate 1-phosphatase activity GO:0042132	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
glucose_6_phosphate_isomerase_activity	ANY_WITH_FUNCTION Gene	glucose-6-phosphate isomerase activity GO:0004347	Participant Unchecked No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.

Gene-review completeness (0/0 grounded genes reviewed)

No concrete UniProt-grounded genes in this module.

Tree

Entner-Doudoroff glycolysis and gluconeogenesisMetabolic Pathwayentner_doudoroff_and_gluconeogenesis

Parts
1. 1. glucose to glucose 6-phosphate
2. Glucose phosphorylationReactionglucokinase_step
  
  Annotons
  - Glucokinase Any With Function: glucokinase activity
3. 2. glucose 6-phosphate oxidation
4. Glucose 6-phosphate to 6-phosphogluconateMetabolic Pathwayglucose_6_phosphate_to_6_phosphogluconate
  
  Parts
  1. 1. glucose 6-phosphate dehydrogenase step
  2. Glucose 6-phosphate dehydrogenaseReactionglucose_6_phosphate_dehydrogenase_step
    
    Annotons
    
    Glucose-6-phosphate dehydrogenase Any With Function: glucose-6-phosphate dehydrogenase activity
  3. 2. 6-phosphogluconolactonase step
  4. 6-phosphogluconolactonaseReactionphosphogluconolactonase_step
    
    Annotons
    
    6-phosphogluconolactonase Any With Function: 6-phosphogluconolactonase activity
5. 3. Entner-Doudoroff committed branch
6. 6-phosphogluconate to pyruvate and glyceraldehyde 3-phosphateMetabolic Pathwayentner_doudoroff_branch
  
  Parts
  1. 1. phosphogluconate dehydratase step
  2. 6-phosphogluconate dehydrataseReactionphosphogluconate_dehydratase_step
    
    Annotons
    
    Phosphogluconate dehydratase Any With Function: phosphogluconate dehydratase activity
  3. 2. KDPG aldolase step
  4. KDPG aldolaseReactionkdpg_aldolase_step
    
    Annotons
    
    2-dehydro-3-deoxy-phosphogluconate aldolase Any With Function: 2-dehydro-3-deoxy-phosphogluconate aldolase activity
7. 4. shared lower EMP trunk
8. Shared lower EMP reactionsMetabolic Pathwaylower_emp_trunk
  
  Parts
  1. 1. triose-phosphate interconversion
  2. Triose-phosphate isomeraseReactiontriose_phosphate_isomerase_step
    
    Annotons
    
    Triose-phosphate isomerase Any With Function: triose-phosphate isomerase activity
  3. 2. glyceraldehyde-3-phosphate dehydrogenase step
  4. Glyceraldehyde-3-phosphate dehydrogenaseReactiongapdh_step
    
    Annotons
    
    NAD-dependent phosphorylating GAPDH Any With Function: glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activity
  5. 3. phosphoglycerate kinase step
  6. Phosphoglycerate kinaseReactionphosphoglycerate_kinase_step
    
    Annotons
    
    Phosphoglycerate kinase Any With Function: phosphoglycerate kinase activity
  7. 4. phosphoglycerate mutase step
  8. Phosphoglycerate mutaseReactionphosphoglycerate_mutase_step
    
    Annotons
    
    Phosphoglycerate mutase Any With Function: phosphoglycerate mutase activity
  9. 5. enolase step
  10. EnolaseReactionenolase_step
    
    Annotons
    
    Phosphopyruvate hydratase Any With Function: phosphopyruvate hydratase activity
  11. 6. pyruvate kinase step
  12. Pyruvate kinaseReactionpyruvate_kinase_step
    
    Annotons
    
    Pyruvate kinase Any With Function: pyruvate kinase activity
9. 5. gluconeogenic bypasses and hexose-phosphate regeneration
10. Gluconeogenic bypass reactionsMetabolic Pathwaygluconeogenic_bypasses
  
  Parts
  1. 1. pyruvate to phosphoenolpyruvate
  2. Pyruvate to phosphoenolpyruvateReactionpyruvate_to_pep_bypass
    
    Variants
    
    Pyruvate-to-PEP enzyme chemistry by enzyme chemistry (One Or More)
    
    Phosphoenolpyruvate synthase routeReactionpep_synthase_variant
    
    Annotons
    
    Phosphoenolpyruvate synthase Any With Function: pyruvate, water dikinase activity
    
    Oxaloacetate-dependent PEP carboxykinase routeReactionpep_carboxykinase_variant
    
    Variants
    
    PEP carboxykinase energy donor variants by energy donor (Exactly One)
    
    GTP-dependent PEP carboxykinaseReactiongtp_pepck_variant
    
    Annotons
    
    GTP-dependent phosphoenolpyruvate carboxykinase Any With Function: phosphoenolpyruvate carboxykinase (GTP) activity
    
    ATP-dependent PEP carboxykinaseReactionatp_pepck_variant
    
    Annotons
    
    ATP-dependent phosphoenolpyruvate carboxykinase Any With Function: phosphoenolpyruvate carboxykinase (ATP) activity
  3. 2. fructose bisphosphate formation and hydrolysis
  4. Fructose 1,6-bisphosphate to fructose 6-phosphateMetabolic Pathwayfructose_bisphosphate_bypass
    
    Parts
    
    1. fructose-bisphosphate aldolase step
    
    Fructose-bisphosphate aldolaseReactionfructose_bisphosphate_aldolase_step
    
    Annotons
    
    Fructose-bisphosphate aldolase Any With Function: fructose-bisphosphate aldolase activity
    
    2. fructose-1,6-bisphosphatase step
    
    Fructose 1,6-bisphosphataseReactionfructose_bisphosphatase_step
    
    Annotons
    
    Fructose 1,6-bisphosphate 1-phosphatase Any With Function: fructose 1,6-bisphosphate 1-phosphatase activity
  5. 3. fructose 6-phosphate to glucose 6-phosphate
  6. Glucose-6-phosphate isomeraseReactionglucose_6_phosphate_isomerase_step
    
    Annotons
    
    Glucose-6-phosphate isomerase Any With Function: glucose-6-phosphate isomerase activity

Details

Context

cytosolGO:0005829

Entner-Doudoroff glycolysis and gluconeogenesisMetabolic Pathwayentner_doudoroff_and_gluconeogenesis

glycolytic process via Entner-Doudoroff PathwayGO:0061678 gluconeogenesisGO:0006094

Context

cytosolGO:0005829

This module deliberately does not model periplasmic glucose oxidation, gluconate/2-ketogluconate loops, or pentose-phosphate recycling as required core parts. Those routes are organism-specific entry or recycling branches that feed 6-phosphogluconate and should be added in a species-specific realization when supported. For P. putida KT2440, KEGG ppu00010 alone is an incomplete satisfiability boundary: the ED branch is satisfied by edd/Q88P43, zwfA/Q88P31, pgl/Q88P30, and eda/Q88P29 even though those genes are assigned through neighboring pentose-phosphate or glutathione-metabolism buckets. Other PSEPK exemplars include glk/Q88P42, gapA/Q88P44 and/or gapB/Q88KZ0, pgk/Q88D64, gpmI/Q88CX4, eno/Q88MF9, pykA/Q88N54 and/or pyk/Q88EZ9, ppsA/Q88L53, fba/Q88D67, fbp/Q88CY9, and pgi1/Q88LW9 plus pgi2/Q88DW7. The PEP synthase route can satisfy pyruvate-to-PEP in KT2440 without requiring a PEP carboxykinase variant.

Connections

glucokinase_step -> glucose_6_phosphate_to_6_phosphogluconate Precedes

glucose_6_phosphate_to_6_phosphogluconate -> entner_doudoroff_branch Precedes

entner_doudoroff_branch -> lower_emp_trunk Provides Input For

The ED branch generates glyceraldehyde 3-phosphate that can enter the lower EMP trunk; it also directly produces pyruvate.

lower_emp_trunk -> gluconeogenic_bypasses Precedes

Lower EMP reactions are reversible or near-reversible except for the terminal pyruvate kinase step; gluconeogenic bypasses regenerate PEP and fructose 6-phosphate when carbon flows toward hexose phosphate.

Part 1: glucose to glucose 6-phosphate

Glucose phosphorylationReactionglucokinase_step

Phosphorylative glucose uptake branches convert D-glucose to D-glucose 6-phosphate before oxidation to 6-phosphogluconate.

Annotons

Glucokinase

glucokinase_activity

Participant: Any With Function: glucokinase activity

Required Function:

glucokinase activityGO:0004340

Function

glucokinase activityGO:0004340

Substrates: D-glucose ATP

Products: D-glucose 6-phosphate ADP

Part 2: glucose 6-phosphate oxidation

Glucose 6-phosphate to 6-phosphogluconateMetabolic Pathwayglucose_6_phosphate_to_6_phosphogluconate

Oxidation of glucose 6-phosphate to 6-phosphogluconate via the glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase steps.

Part 1: glucose 6-phosphate dehydrogenase step

Glucose 6-phosphate dehydrogenaseReactionglucose_6_phosphate_dehydrogenase_step

Annotons

Glucose-6-phosphate dehydrogenase

glucose_6_phosphate_dehydrogenase_activity

Participant: Any With Function: glucose-6-phosphate dehydrogenase activity

Required Function:

glucose-6-phosphate dehydrogenase activityGO:0004345

Function

glucose-6-phosphate dehydrogenase activityGO:0004345

Substrates: D-glucose 6-phosphate NADP+

Products: 6-phospho-D-glucono-1,5-lactone NADPH

Part 2: 6-phosphogluconolactonase step

6-phosphogluconolactonaseReactionphosphogluconolactonase_step

Annotons

6-phosphogluconolactonase

phosphogluconolactonase_activity

Participant: Any With Function: 6-phosphogluconolactonase activity

Required Function:

6-phosphogluconolactonase activityGO:0017057

Function

6-phosphogluconolactonase activityGO:0017057

Substrates: 6-phospho-D-glucono-1,5-lactone

Products: 6-phospho-D-gluconate

Part 3: Entner-Doudoroff committed branch

6-phosphogluconate to pyruvate and glyceraldehyde 3-phosphateMetabolic Pathwayentner_doudoroff_branch

Entner-Doudoroff pathway through 6-phosphogluconateGO:0061678

Part 1: phosphogluconate dehydratase step

6-phosphogluconate dehydrataseReactionphosphogluconate_dehydratase_step

Annotons

Phosphogluconate dehydratase

phosphogluconate_dehydratase_activity

Participant: Any With Function: phosphogluconate dehydratase activity

Required Function:

phosphogluconate dehydratase activityGO:0004456

Function

phosphogluconate dehydratase activityGO:0004456

Substrates: 6-phospho-D-gluconate

Products: 2-dehydro-3-deoxy-6-phospho-D-gluconate

Part 2: KDPG aldolase step

KDPG aldolaseReactionkdpg_aldolase_step

Annotons

2-dehydro-3-deoxy-phosphogluconate aldolase

kdpg_aldolase_activity

Participant: Any With Function: 2-dehydro-3-deoxy-phosphogluconate aldolase activity

Required Function:

2-dehydro-3-deoxy-phosphogluconate aldolase activityGO:0008675

Function

2-dehydro-3-deoxy-phosphogluconate aldolase activityGO:0008675

Substrates: 2-dehydro-3-deoxy-6-phospho-D-gluconate

Products: pyruvate D-glyceraldehyde 3-phosphate

Part 4: shared lower EMP trunk

Shared lower EMP reactionsMetabolic Pathwaylower_emp_trunk

pyruvate kinase activityGO:0004743

Part 5: gluconeogenic bypasses and hexose-phosphate regeneration

Gluconeogenic bypass reactionsMetabolic Pathwaygluconeogenic_bypasses

gluconeogenesisGO:0006094

Part 1: pyruvate to phosphoenolpyruvate

Pyruvate to phosphoenolpyruvateReactionpyruvate_to_pep_bypass

Variant set: Pyruvate-to-PEP enzyme chemistry by enzyme chemistry (One Or More)

Phosphoenolpyruvate synthase routeReactionpep_synthase_variant

Annotons

Phosphoenolpyruvate synthase

pep_synthase_activity

Participant: Any With Function: pyruvate, water dikinase activity

Required Function:

pyruvate, water dikinase activityGO:0008986

Function

pyruvate, water dikinase activityGO:0008986

Oxaloacetate-dependent PEP carboxykinase routeReactionpep_carboxykinase_variant

Some organisms route pyruvate-derived carbon through oxaloacetate and phosphoenolpyruvate carboxykinase.

Variant set: PEP carboxykinase energy donor variants by energy donor (Exactly One)

GTP-dependent PEP carboxykinaseReactiongtp_pepck_variant

Annotons

GTP-dependent phosphoenolpyruvate carboxykinase

gtp_pepck_activity

Participant: Any With Function: phosphoenolpyruvate carboxykinase (GTP) activity

Required Function:

phosphoenolpyruvate carboxykinase (GTP) activityGO:0004613

Function

phosphoenolpyruvate carboxykinase (GTP) activityGO:0004613

ATP-dependent PEP carboxykinaseReactionatp_pepck_variant

Annotons

ATP-dependent phosphoenolpyruvate carboxykinase

atp_pepck_activity

Participant: Any With Function: phosphoenolpyruvate carboxykinase (ATP) activity

Required Function:

phosphoenolpyruvate carboxykinase (ATP) activityGO:0004612

Function

phosphoenolpyruvate carboxykinase (ATP) activityGO:0004612

Part 2: fructose bisphosphate formation and hydrolysis

glucose-6-phosphate isomerase activityGO:0004347