Glycolysis II — payoff phase (glyceraldehyde-3-phosphate → pyruvate); PGK/PGAM/enolase/PK deficiencies

The payoff (energy-yielding) phase of glycolysis is the second half of the cytosolic pathway, converting each glyceraldehyde-3-phosphate produced in the investment phase into pyruvate while generating ATP and NADH. Five steps: glyceraldehyde-3-phosphate dehydrogenase (GAPDH) oxidises and phosphorylates glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, reducing NAD+ to NADH; phosphoglycerate kinase (PGK1) transfers a phosphate from 1,3-bisphosphoglycerate to ADP, forming 3-phosphoglycerate and the first ATP (substrate-level phosphorylation); phosphoglycerate mutase (muscle PGAM2) isomerises 3-phosphoglycerate to 2-phosphoglycerate; enolase (muscle ENO3) dehydrates 2-phosphoglycerate to phosphoenolpyruvate; and pyruvate kinase (liver/RBC PKLR, or muscle/other PKM) transfers the phosphate of phosphoenolpyruvate to ADP, forming pyruvate and the second ATP. Per glucose (two trioses) the payoff phase yields 4 ATP and 2 NADH, for a net glycolytic gain of 2 ATP + 2 NADH + 2 pyruvate. Because mature erythrocytes rely entirely on glycolytic ATP, defects here characteristically cause hereditary nonspherocytic hemolytic anemia, often combined with tissue-specific features: PGK1 deficiency (X-linked hemolytic anemia + myopathy + CNS disease); PGAM2 deficiency = glycogen storage disease type X (muscle); ENO3 deficiency = GSD type XIII (muscle); and PKLR deficiency = pyruvate kinase deficiency, the commonest glycolytic cause of hemolytic anemia.

MODULE:glycolysis_payoff_phaseDRAFTMetabolic Pathwaymodules/glycolysis_payoff_phase.yaml
glycolytic processGO:0006096
GO:0006096
glycolytic process
The module is grounded in the GO glycolytic process (GO:0006096); it covers the payoff-phase steps from glyceraldehyde-3-phosphate to pyruvate.
Reactome:R-HSA-70171
Glycolysis
Step order and reaction stoichiometries follow the human Reactome "Glycolysis" reactions R-HSA-70449 (GAPDH), R-HSA-71850 (PGK1), R-HSA-71654 (PGAM), R-HSA-71660 (enolase) and R-HSA-71670 (pyruvate kinase).
file:human/GAPDH/GAPDH-ai-review.yaml
GAPDH gene review (human)
The glyceraldehyde-3-phosphate dehydrogenase step (UniProtKB:P04406, GO:0004365) matches the previously completed human GAPDH review (already on main).
file:human/PGK1/PGK1-ai-review.yaml
PGK1 gene review (human)
The phosphoglycerate kinase step (UniProtKB:P00558, GO:0004618) matches the completed human PGK1 review.
file:human/PGAM2/PGAM2-ai-review.yaml
PGAM2 gene review (human)
The phosphoglycerate mutase step (UniProtKB:P15259, GO:0004619) matches the completed human PGAM2 review.
file:human/ENO3/ENO3-ai-review.yaml
ENO3 gene review (human)
The enolase step (UniProtKB:P13929, GO:0004634) matches the completed human ENO3 review.
file:human/PKLR/PKLR-ai-review.yaml
PKLR gene review (human)
The pyruvate kinase step (UniProtKB:P30613, GO:0004743) matches the completed human PKLR review.
file:human/PKM/PKM-ai-review.yaml
PKM gene review (human)
The muscle/other pyruvate kinase isozyme of the final step (UniProtKB:P14618, GO:0004743) matches the previously completed human PKM review (already on main).
6Nodes
5Parts
0Variant Sets
0Variants
5Annotons
4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:glycolysis_payoff_phase 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 (6/6 grounded genes reviewed)

6 complete review(s) · 2 with deep research · 0 missing review · 4 reviewed but lacking deep research

Gene Review Complete Deep research
ENO3 P13929 ✓ ✓ ✗
GAPDH P04406 ✓ ✓ ✓
PGAM2 P15259 ✓ ✓ ✗
PGK1 P00558 ✓ ✓ ✗
PKLR P30613 ✓ ✓ ✗
PKM P14618 ✓ ✓ ✓

Details

Context
cytosolGO:0005829
Glycolysis (payoff phase)Metabolic Pathwayglycolysis_payoff_phase
glycolytic processGO:0006096
Context
cytosolGO:0005829

Five-step payoff phase of glycolysis grounded to the human enzymes GAPDH (UniProtKB:P04406, GO:0004365), phosphoglycerate kinase PGK1 (P00558, GO:0004618), phosphoglycerate mutase PGAM2 (P15259, GO:0004619), beta-enolase ENO3 (P13929, GO:0004634) and pyruvate kinase PKLR (P30613) / PKM (P14618) (GO:0004743). GO molecular-function terms were taken from the human GOA records; Reactome reaction ids and titles were verified against the local reactome cache. Each step uses a PANTHER family selector generic over the tissue isozymes and orthologs (PGAM node covers PGAM1/PGAM2/BPGM; enolase node ENO1/ENO2/ENO3; pyruvate-kinase node PKLR + PKM). GAPDH and PKM were reviewed previously (already on main) and are cross-linked via file: evidence; PGK1/PGAM2/ENO3/PKLR are the reviews new in this batch. Upstream, the two glyceraldehyde-3-phosphate molecules come from the glycolysis investment phase (hexokinase -> GPI -> PFK -> aldolase -> TPI); downstream, pyruvate feeds the pyruvate-metabolism module (PDC/PC) and lactate fermentation (LDHA/LDHB, a separate module), while the reverse reactions (except the PFK/PK/hexokinase committed steps) serve gluconeogenesis. Moonlighting roles (GAPDH; PGK1 extracellular reductase; PKM2 nuclear/protein-kinase) are captured non-core in the individual gene reviews. Disorders: PGK1 (X-linked hemolytic anemia + myopathy + CNS); PGAM2 (GSD X); ENO3 (GSD XIII); PKLR (pyruvate kinase deficiency, hemolytic anemia).

Connections

gapdh_step -> pgk_step Provides Input For
1,3-bisphosphoglycerate from GAPDH is the substrate for PGK1.
pgk_step -> pgam_step Provides Input For
3-phosphoglycerate from PGK1 is isomerised by PGAM.
pgam_step -> enolase_step Provides Input For
2-phosphoglycerate from PGAM is dehydrated by enolase.
enolase_step -> pk_step Provides Input For
Phosphoenolpyruvate from enolase is converted to pyruvate by pyruvate kinase.
Part 1: oxidative phosphorylation of the triose (NAD+ reduction)
D-glyceraldehyde-3-phosphate + NAD+ + Pi to 1,3-bisphosphoglycerate + NADHReactiongapdh_step

Annotons

GAPDH: glyceraldehyde-3-phosphate dehydrogenase
gapdh_activity
Participant: Family: Glyceraldehyde-3-phosphate dehydrogenase family (GAPDH/GAPDHS)
Family:
Glyceraldehyde-3-phosphate dehydrogenase family (GAPDH/GAPDHS)PANTHER:PTHR10836
Representative Members: GAPDH (human)UniProtKB:P04406

Function

glyceraldehyde-3-phosphate dehydrogenase (NAD+) (phosphorylating) activityGO:0004365
Substrates: D-glyceraldehyde 3-phosphate NAD+ phosphate
Products: 1,3-bisphospho-D-glycerate NADH

Locations

cytosolGO:0005829

Couples oxidation of glyceraldehyde-3-phosphate to formation of the high-energy acyl-phosphate 1,3-bisphosphoglycerate and reduction of NAD+ to NADH (reviewed previously; also a well-known moonlighting protein).

Part 2: first substrate-level ATP generation
1,3-bisphosphoglycerate + ADP to 3-phosphoglycerate + ATPReactionpgk_step

Annotons

PGK1/PGK2: phosphoglycerate kinase
pgk_activity
Participant: Family: Phosphoglycerate kinase family (PGK1/PGK2)
Family:
Phosphoglycerate kinase family (PGK1/PGK2)PANTHER:PTHR11406
Representative Members: PGK1 (human, somatic)UniProtKB:P00558

Function

phosphoglycerate kinase activityGO:0004618
Substrates: 1,3-bisphospho-D-glycerate ADP
Products: 3-phospho-D-glycerate ATP

Locations

cytosolGO:0005829

Generates the first ATP of glycolysis by substrate-level phosphorylation (reverse direction in gluconeogenesis). X-linked PGK1 deficiency causes hemolytic anemia with myopathy and CNS disease; PGK2 is testis-specific.

Part 3: phosphoglycerate isomerisation
3-phosphoglycerate to 2-phosphoglycerateReactionpgam_step

Annotons

PGAM1/PGAM2: phosphoglycerate mutase
pgam_activity
Participant: Family: Cofactor-dependent phosphoglycerate mutase family (PGAM1/PGAM2/BPGM)
Family:
Cofactor-dependent phosphoglycerate mutase family (PGAM1/PGAM2/BPGM)PANTHER:PTHR11931
Representative Members: PGAM2 (human, muscle isozyme)UniProtKB:P15259

Function

phosphoglycerate mutase activityGO:0004619
Substrates: 3-phospho-D-glycerate
Products: 2-phospho-D-glycerate

Locations

cytosolGO:0005829

Interconverts 3- and 2-phosphoglycerate (dimer of the muscle PGAM2/M and brain PGAM1/B subunits; muscle = PGAM2 homodimer). PGAM2 deficiency = GSD type X (exercise intolerance, myoglobinuria).

Part 4: dehydration to the high-energy enol phosphate
2-phosphoglycerate to phosphoenolpyruvate + H2OReactionenolase_step

Annotons

ENO1/ENO2/ENO3: enolase (phosphopyruvate hydratase)
enolase_activity
Participant: Family: Enolase family (ENO1/ENO2/ENO3)
Family:
Enolase family (ENO1/ENO2/ENO3)PANTHER:PTHR11902
Representative Members: ENO3 (human, muscle beta-enolase)UniProtKB:P13929

Function

phosphopyruvate hydratase activityGO:0004634
Substrates: 2-phospho-D-glycerate
Products: phosphoenolpyruvate water

Locations

cytosolGO:0005829

Mg2+-dependent dehydration of 2-phosphoglycerate to phosphoenolpyruvate. Tissue isozymes ENO1 (alpha, ubiquitous), ENO2 (gamma, neuronal), ENO3 (beta, muscle); ENO3 deficiency = GSD type XIII.

Part 5: second substrate-level ATP generation (final, committed)
phosphoenolpyruvate + ADP to pyruvate + ATPReactionpk_step

Annotons

PKM/PKLR: pyruvate kinase
pk_activity
Participant: Family: Pyruvate kinase family (PKM/PKLR)
Family:
Pyruvate kinase family (PKM/PKLR)PANTHER:PTHR11817
Representative Members: PKLR (human, liver/red-cell isozyme)UniProtKB:P30613 PKM (human, muscle/M1-M2 isozyme)UniProtKB:P14618

Function

pyruvate kinase activityGO:0004743
Substrates: phosphoenolpyruvate ADP
Products: pyruvate ATP

Locations

cytosolGO:0005829

Final, essentially irreversible glycolytic step generating the second ATP; homotetramer, Mg2+/K+-dependent, allosterically activated by fructose-1,6-bisphosphate. PKLR (liver/RBC) deficiency = pyruvate kinase deficiency (commonest glycolytic hemolytic anemia); PKM = muscle/other.