Pentose phosphate pathway — non-oxidative branch + PRPP synthesis; transaldolase/RPIA deficiency, PRPS1 disorders

The non-oxidative branch of the pentose phosphate pathway is a set of reversible sugar-phosphate rearrangements that interconvert the five-carbon sugar ribulose-5-phosphate (from the oxidative branch) with ribose-5-phosphate for nucleotide synthesis and with the glycolytic intermediates fructose-6-phosphate and glyceraldehyde-3-phosphate — allowing cells to balance their demand for NADPH versus ribose-5-phosphate. Ribose-5-phosphate isomerase (RPIA) interconverts ribulose-5-phosphate and ribose-5-phosphate; ribulose-5-phosphate 3-epimerase (RPE) interconverts ribulose-5-phosphate and xylulose-5-phosphate; transketolase (TKT, thiamine-diphosphate-dependent) transfers two-carbon units, converting xylulose-5-phosphate + ribose-5-phosphate to sedoheptulose-7-phosphate + glyceraldehyde-3-phosphate (and, in a second reaction, xylulose-5-phosphate + erythrose-4-phosphate to fructose-6-phosphate + glyceraldehyde-3-phosphate); and transaldolase (TALDO1) transfers a three-carbon unit, converting sedoheptulose-7-phosphate + glyceraldehyde-3-phosphate to erythrose-4-phosphate + fructose-6-phosphate. Finally, phosphoribosyl pyrophosphate synthetase (PRPS1) uses ribose-5-phosphate + ATP to make 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) + AMP — the activated precursor that commits pentose carbon to de novo and salvage synthesis of purine, pyrimidine and pyridine (NAD) nucleotides. Inherited defects: transaldolase (TALDO1) deficiency causes liver disease and hemolytic anemia; ribose-5-phosphate isomerase (RPIA) deficiency is an extremely rare progressive leukoencephalopathy; and PRPS1 loss-of-function causes Arts syndrome / CMTX5 / DFN2 while gain-of-function (superactivity) causes purine overproduction with gout.

MODULE:pentose_phosphate_nonoxidative_branchDRAFTMetabolic Pathwaymodules/pentose_phosphate_nonoxidative_branch.yaml
pentose-phosphate shunt, non-oxidative branchGO:0009052
GO:0009052
pentose-phosphate shunt, non-oxidative branch
The module is grounded in the GO pentose-phosphate shunt, non-oxidative branch (GO:0009052), plus the PRPP-synthesis exit to nucleotide metabolism.
Reactome:R-HSA-71336
Pentose phosphate pathway
Reactions follow the human Reactome "Pentose phosphate pathway" (R-HSA-71336): R-HSA-177784 (RPIA), R-HSA-71303 (RPE), R-HSA-71324 (TKT), R-HSA-71334 (TALDO1) and R-HSA-73580 (PRPS1).
file:human/RPIA/RPIA-ai-review.yaml
RPIA gene review (human)
The ribose-5-phosphate isomerase step (UniProtKB:P49247, GO:0004751) matches the completed human RPIA review.
file:human/RPE/RPE-ai-review.yaml
RPE gene review (human)
The ribulose-5-phosphate 3-epimerase step (UniProtKB:Q96AT9, GO:0004750) matches the completed human RPE review.
file:human/TKT/TKT-ai-review.yaml
TKT gene review (human)
The transketolase step (UniProtKB:P29401, GO:0004802) matches the completed human TKT review.
file:human/TALDO1/TALDO1-ai-review.yaml
TALDO1 gene review (human)
The transaldolase step (UniProtKB:P37837, GO:0004801) matches the completed human TALDO1 review.
file:human/PRPS1/PRPS1-ai-review.yaml
PRPS1 gene review (human)
The PRPP-synthesis exit step (UniProtKB:P60891, GO:0004749) matches the completed human PRPS1 review.
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:pentose_phosphate_nonoxidative_branch 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 (5/5 grounded genes reviewed)

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

Gene Review Complete Deep research
PRPS1 P60891 ✓ ✓ ✗
RPE Q96AT9 ✓ ✓ ✗
RPIA P49247 ✓ ✓ ✗
TALDO1 P37837 ✓ ✓ ✗
TKT P29401 ✓ ✓ ✗

Details

Context
cytosolGO:0005829
Pentose phosphate pathway (non-oxidative branch + PRPP)Metabolic Pathwaypentose_phosphate_nonoxidative_branch
pentose-phosphate shunt, non-oxidative branchGO:0009052
Context
cytosolGO:0005829

Non-oxidative branch of the pentose phosphate pathway plus the PRPP-synthesis exit, grounded to the human enzymes RPIA (UniProtKB:P49247, GO:0004751, EC 5.3.1.6), RPE (Q96AT9, GO:0004750, EC 5.1.3.1), transketolase TKT (P29401, GO:0004802, EC 2.2.1.1), transaldolase TALDO1 (P37837, GO:0004801, EC 2.2.1.2) and PRPP synthetase PRPS1 (P60891, GO:0004749, EC 2.7.6.1). 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 paralogs/orthologs; e.g. TKT family includes TKTL1/TKTL2, PRPS family includes PRPS2). These reactions are reversible and non-linear: ribulose-5-phosphate from the oxidative branch (G6PD/PGLS/PGD module) is split by RPIA (-> ribose-5-P) and RPE (-> xylulose-5-P) into the transketolase/transaldolase carbon shuffle that regenerates glycolytic fructose-6-phosphate and glyceraldehyde-3-phosphate; transketolase also runs a second reaction (xylulose-5-P + erythrose-4-P <-> fructose-6-P + glyceraldehyde-3-P), not modelled as a separate node. PRPS1 is the committed exit that channels ribose-5-phosphate to PRPP for purine/pyrimidine/NAD synthesis and salvage (the PRPP used by HPRT1/APRT of the purine_salvage_and_catabolism module). Disorders: TALDO1 -> transaldolase deficiency (hepatopathy + hemolysis); RPIA -> leukoencephalopathy (very rare); PRPS1 -> Arts syndrome / CMTX5 / DFN2 (loss) and PRPP synthetase superactivity / gout (gain); TKT indexes thiamine status; RPE has no common Mendelian disease.

Connections

rpia_step -> tkt_step Provides Input For
Ribose-5-phosphate from RPIA is a transketolase substrate.
rpe_step -> tkt_step Provides Input For
Xylulose-5-phosphate from RPE is the other transketolase substrate.
tkt_step -> taldo1_step Provides Input For
Sedoheptulose-7-phosphate + glyceraldehyde-3-phosphate from transketolase are the transaldolase substrates.
rpia_step -> prps1_step Provides Input For
Ribose-5-phosphate from RPIA is committed to nucleotide synthesis by PRPS1 (PRPP).
Part 1: ribulose-5-P / ribose-5-P isomerisation
D-ribulose-5-phosphate to D-ribose-5-phosphateReactionrpia_step

Annotons

RPIA: ribose-5-phosphate isomerase
rpia_activity
Participant: Family: Ribose-5-phosphate isomerase family (RPIA)
Family:
Ribose-5-phosphate isomerase family (RPIA)PANTHER:PTHR11934
Representative Members: RPIA (human)UniProtKB:P49247

Function

ribose-5-phosphate isomerase activityGO:0004751
Substrates: D-ribulose 5-phosphate
Products: D-ribose 5-phosphate

Locations

cytosolGO:0005829

Interconverts ribulose-5-phosphate and ribose-5-phosphate, supplying ribose-5-phosphate for nucleotide synthesis (via PRPS1). Deficiency causes a very rare progressive leukoencephalopathy.

Part 2: ribulose-5-P / xylulose-5-P epimerisation
D-ribulose-5-phosphate to D-xylulose-5-phosphateReactionrpe_step

Annotons

RPE: ribulose-5-phosphate 3-epimerase
rpe_activity
Participant: Family: Ribulose-phosphate 3-epimerase family (RPE)
Family:
Ribulose-phosphate 3-epimerase family (RPE)PANTHER:PTHR11749
Representative Members: RPE (human)UniProtKB:Q96AT9

Function

D-ribulose-phosphate 3-epimerase activityGO:0004750
Substrates: D-ribulose 5-phosphate
Products: D-xylulose 5-phosphate

Locations

cytosolGO:0005829

Interconverts ribulose-5-phosphate and xylulose-5-phosphate, supplying the xylulose-5-phosphate substrate for transketolase. No common Mendelian disease.

Part 3: two-carbon transfer (transketolase)
D-xylulose-5-P + D-ribose-5-P to sedoheptulose-7-P + D-glyceraldehyde-3-PReactiontkt_step

Annotons

TKT: transketolase
tkt_activity
Participant: Family: Transketolase family (TKT/TKTL1/TKTL2)
Family:
Transketolase family (TKT/TKTL1/TKTL2)PANTHER:PTHR43195
Representative Members: TKT (human)UniProtKB:P29401

Function

transketolase activityGO:0004802
Substrates: D-xylulose 5-phosphate D-ribose 5-phosphate
Products: sedoheptulose 7-phosphate D-glyceraldehyde 3-phosphate

Locations

cytosolGO:0005829

Thiamine-diphosphate-dependent enzyme transferring 2-carbon units; links the pentose phosphate pathway to glycolysis (fructose-6-P, glyceraldehyde-3-P). Erythrocyte TKT activity indexes thiamine (B1) status.

Part 4: three-carbon transfer (transaldolase)
sedoheptulose-7-P + D-glyceraldehyde-3-P to D-erythrose-4-P + D-fructose-6-PReactiontaldo1_step

Annotons

TALDO1: transaldolase
taldo1_activity
Participant: Family: Transaldolase family (TALDO1)
Family:
Transaldolase family (TALDO1)PANTHER:PTHR10683
Representative Members: TALDO1 (human)UniProtKB:P37837

Function

transaldolase activityGO:0004801
Substrates: sedoheptulose 7-phosphate D-glyceraldehyde 3-phosphate
Products: D-erythrose 4-phosphate D-fructose 6-phosphate

Locations

cytosolGO:0005829

Transfers a 3-carbon unit, completing the reversible connection of pentose phosphates to glycolytic fructose-6-phosphate and generating erythrose-4-phosphate. Deficiency causes transaldolase deficiency (liver cirrhosis, hemolytic anemia).

Part 5: exit to nucleotide synthesis (PRPP)
D-ribose-5-phosphate + ATP to PRPP + AMPReactionprps1_step

Annotons

PRPS1: phosphoribosyl pyrophosphate synthetase 1
prps1_activity
Participant: Family: Ribose-phosphate diphosphokinase family (PRPS1/PRPS2)
Family:
Ribose-phosphate diphosphokinase family (PRPS1/PRPS2)PANTHER:PTHR10210
Representative Members: PRPS1 (human)UniProtKB:P60891

Function

ribose phosphate diphosphokinase activityGO:0004749
Substrates: D-ribose 5-phosphate ATP
Products: 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) AMP

Locations

cytosolGO:0005829

Makes PRPP from ribose-5-phosphate + ATP — the activated precursor committing pentose carbon to de novo/salvage purine, pyrimidine and NAD nucleotide synthesis (the substrate of HGPRT/APRT). Loss = Arts/CMTX5/DFN2; gain = superactivity/gout.