Cytosolic NADPH regeneration in Drosophila melanogaster

NADPH supplies reducing power for fatty acid synthesis and for antioxidant systems such as glutathione and thioredoxin reduction. In Drosophila, as in other animals, it is regenerated outside mitochondria by three sets of NADP-dependent dehydrogenases. The oxidative branch of the pentose phosphate pathway produces two NADPH per glucose 6-phosphate through glucose-6-phosphate dehydrogenase (G6pd, Zw) and 6-phosphogluconate dehydrogenase (Pgd). NADP-dependent isocitrate dehydrogenase (Idh) oxidizes isocitrate to 2-oxoglutarate, and NADP-dependent malic enzyme (Men) decarboxylates malate to pyruvate, each reducing NADP+. Studies of fly mutants and allozyme variants link these enzymes to lipid accumulation.

MODULE:dmel_cytosolic_nadph_regenerationDRAFTCONCRETEMetabolic Pathwaymodules/dmel_cytosolic_nadph_regeneration.yaml
NADPH regenerationGO:0006740
FB:FBgg0002243
FlyBase gene group NADPHRE: Nadph regeneration
FlyBase release FB2026_03 groups 5 D. melanogaster genes as nadph regeneration (NADPHRE); this module models that group.
GO:0006740
NADPH regeneration
GO term grounding the module as NADPH regeneration.

Boundary. The module covers the five FlyBase NADPH regeneration enzymes. The three parts are parallel sources of NADPH and are not linked by connections. The 6-phosphogluconolactonase step between G6pd and Pgd is not a FlyBase member and is not modelled. Mitochondrial NADPH sources (for example nicotinamide nucleotide transhydrogenase) are outside the module. FlyBase groups realized by this module: NADPHRE (FBgg0002243). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_cytosolic_nadph_regeneration.yaml. Member genes with a gene review in this repository: G6pd, Idh, Men, Men-b, Pgd.

6Nodes
5Parts
0Variant Sets
0Variants
5Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_cytosolic_nadph_regeneration 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.

Function consistency and core coverage

4 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (4 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
g6p_dehydrogenation_g6pd G6pd
UniProtKB:P12646
Gene
glucose-6-phosphate dehydrogenase activity
GO:0004345
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
phosphogluconate_decarboxylation_pgd Pgd
UniProtKB:P41572
Gene
phosphogluconate dehydrogenase (decarboxylating) activity
GO:0004616
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
isocitrate_oxidation_idh Idh
UniProtKB:B7Z0E0
Gene
isocitrate dehydrogenase (NADP+) activity
GO:0004450
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
malate_decarboxylation_men Men
UniProtKB:Q9VG31
Gene
malate dehydrogenase (decarboxylating) (NADP+) activity
GO:0004473
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).

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

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

Gene Review Complete Deep research
G6pd P12646 ✓ ✓ ✓
Idh B7Z0E0 ✓ ✓ ✓
Men Q9VG31 ✓ ✓ ✓
Men-b E1JIZ4 ✓ ✓ ✓
Pgd P41572 ✓ ✓ ✓

Details

Context
Drosophila melanogasterNCBITaxon:7227
Cytosolic NADPH regenerationMetabolic Pathwaydmel_cytosolic_nadph_regeneration

NADPH regeneration by the oxidative pentose phosphate pathway (G6pd, Pgd), NADP-isocitrate dehydrogenase (Idh) and malic enzymes (Men, Men-b).

NADPH regenerationGO:0006740
Context
Drosophila melanogasterNCBITaxon:7227
Part 1: glucose 6-phosphate to ribulose 5-phosphate with two NADPH
Oxidative pentose phosphate pathwayMetabolic Pathwayoxidative_pentose_phosphate

Connections

6-phosphogluconate, formed from the G6pd product by lactonase, is oxidized by Pgd.
Part 1: glucose 6-phosphate to 6-phosphogluconolactone
Glucose 6-phosphate dehydrogenationMetabolic Pathwayg6p_dehydrogenation

Annotons

G6pd Glucose 6-phosphate dehydrogenation
g6p_dehydrogenation_g6pd
Participant: Gene Product: G6pd
Gene Product:

Function

glucose-6-phosphate dehydrogenase activityGO:0004345
Part 2: 6-phosphogluconate to ribulose 5-phosphate
6-Phosphogluconate oxidative decarboxylationMetabolic Pathwayphosphogluconate_decarboxylation

Annotons

Pgd 6-Phosphogluconate oxidative decarboxylation
phosphogluconate_decarboxylation_pgd
Participant: Gene Product: Pgd
Gene Product:

Function

phosphogluconate dehydrogenase (decarboxylating) activityGO:0004616
Part 2: isocitrate to 2-oxoglutarate with NADPH
NADP-isocitrate oxidationMetabolic Pathwayisocitrate_oxidation

Annotons

Idh NADP-isocitrate oxidation
isocitrate_oxidation_idh
Participant: Gene Product: Idh
Gene Product:

Function

isocitrate dehydrogenase (NADP+) activityGO:0004450
Part 3: malate to pyruvate with NADPH
NADP-malic enzyme decarboxylationMetabolic Pathwaymalate_decarboxylation

Men is the main NADP-malic enzyme; Men-b is a paralog whose activity has not been characterized.

Annotons

Men NADP-malic enzyme decarboxylation
malate_decarboxylation_men
Participant: Gene Product: Men
Gene Product:

Function

malate dehydrogenase (decarboxylating) (NADP+) activityGO:0004473
Men-b NADP-malic enzyme decarboxylation
malate_decarboxylation_men_b
Participant: Gene Product: Men-b
Gene Product: