Flavin cofactor biosynthesis (riboflavin -> FMN -> FAD; RFK + FLAD1)

Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the redox cofactors of the flavoproteins — respiratory Complex I and II, the acyl-CoA dehydrogenases of fatty-acid oxidation, MTHFR, PNPO, kynurenine 3-monooxygenase and hundreds of others. Because humans cannot make the riboflavin (vitamin B2) ring de novo, dietary riboflavin is converted intracellularly to its active cofactor forms in two committed steps. Riboflavin kinase (RFK) first phosphorylates riboflavin with ATP (and a divalent metal) to FMN. FAD synthase (FLAD1, an FMN adenylyltransferase) then adenylylates FMN with ATP to FAD; human FLAD1 has isoforms differing in an N-terminal molybdopterin-binding/KH region and additionally shows FAD-diphosphatase (FAD-hydrolysing) activity that reverses the last step and can act as a flavin chaperone for apo-flavoproteins. The pathway is the sole supply of flavin cofactors: inherited FLAD1 deficiency causes a lipid-storage myopathy with combined respiratory-chain / multiple-acyl-CoA-dehydrogenase deficiency, part of which is riboflavin-responsive.

MODULE:flavin_cofactor_biosynthesisDRAFTMetabolic Pathwaymodules/flavin_cofactor_biosynthesis.yaml
FAD biosynthetic processGO:0006747 FMN biosynthetic processGO:0009398
GO:0006747
FAD biosynthetic process
The pathway carries out FAD biosynthesis (GO:0006747) from riboflavin.
GO:0009398
FMN biosynthetic process
RFK carries out FMN biosynthesis (GO:0009398), the first committed step.
file:human/RFK/RFK-ai-review.yaml
RFK gene review (human)
The riboflavin->FMN step (UniProtKB:Q969G6, GO:0008531) matches the completed human RFK review.
file:human/FLAD1/FLAD1-ai-review.yaml
FLAD1 gene review (human)
The FMN->FAD step (UniProtKB:Q8NFF5, GO:0003919) matches the completed human FLAD1 review.
3Nodes
2Parts
0Variant Sets
0Variants
2Annotons
1Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:flavin_cofactor_biosynthesis 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 (2/2 grounded genes reviewed)

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

Gene Review Complete Deep research
FLAD1 Q8NFF5 ✓ ✓ ✗
RFK Q969G6 ✓ ✓ ✗

Details

Context
cytosolGO:0005829
Flavin cofactor biosynthesis (riboflavin -> FMN -> FAD)Metabolic Pathwayflavin_cofactor_biosynthesis
FAD biosynthetic processGO:0006747 FMN biosynthetic processGO:0009398
Context
cytosolGO:0005829

Flavin cofactor biosynthesis (GO:0006747 FAD; GO:0009398 FMN) from dietary riboflavin, grounded to the completed human gene reviews: RFK (Q969G6, GO:0008531 riboflavin kinase + ATP/metal — humans do not synthesise the riboflavin ring, so its riboflavin-biosynthesis IEAs were corrected to riboflavin metabolic process) and the bifunctional FLAD1 (Q8NFF5, GO:0003919 FMN adenylyltransferase + a second FAD-diphosphatase/chaperone activity). Both are (largely) cytosolic; some FLAD1 isoforms are mitochondrial. FMN and FAD are the cofactors of the flavoenzymes curated across these modules — respiratory Complex I (NDUFV1) and II (SDHA), the acyl-CoA dehydrogenases (GCDH), PRODH, KMO, PNPO, FOXRED1, MTHFR and others. GO term ids/labels verified against the local go.db. Disorders: FLAD1 deficiency — lipid-storage myopathy with combined respiratory-chain/multiple-acyl-CoA-dehydrogenase deficiency (partly riboflavin-responsive); dietary riboflavin deficiency broadly impairs flavoenzyme function.

Connections

riboflavin_to_fmn -> fmn_to_fad Provides Input For
The FMN produced by RFK is the substrate for FLAD1, which adenylylates it to FAD.
Part 1: riboflavin phosphorylation to FMN
Riboflavin kinase (RFK)Reactionriboflavin_to_fmn

Annotons

RFK: riboflavin kinase
rfk_activity
Participant: Family: RFK / riboflavin kinase family
Family:
RFK / riboflavin kinase familyPANTHER:PTHR22749
Representative Members: RFK (human)UniProtKB:Q969G6

Function

riboflavin kinase activityGO:0008531
Substrates: riboflavin (vitamin B2) ATP (with Zn2+/Mg2+)
Products: FMN (flavin mononucleotide)

Locations

cytosolGO:0005829

Phosphorylates riboflavin to FMN.

Part 2: FMN adenylylation to FAD
FAD synthase (FLAD1)Reactionfmn_to_fad

Annotons

FLAD1: FAD synthase (FMN adenylyltransferase)
flad1_activity
Participant: Family: FLAD1 / FAD synthase family
Family:
FLAD1 / FAD synthase familyPANTHER:PTHR23293
Representative Members: FLAD1 (human)UniProtKB:Q8NFF5

Function

FMN adenylyltransferase activityGO:0003919
Substrates: FMN ATP (with Mg2+)
Products: FAD (flavin adenine dinucleotide) diphosphate

Locations

cytosolGO:0005829

Adenylylates FMN to FAD (final step; also a flavin chaperone).