Folate one-carbon carrier-state interconversionMetabolic Pathwayfolate_one_carbon_interconversion
The module is organized by carrier-state chemistry rather than by one particular multidomain protein or species. Molecular-function terms are on leaf annotons. PANTHER families and selective UniProt representatives orient enzyme architecture and cofactor variants; exact PTNs are used only where the local canonical PAINT file carries the corresponding IBD assertion. Cofactor variants are defined by verified reaction and architecture rather than by taxonomic kingdom. The core dehydrogenase and cyclohydrolase operations are required, while the MTHFR and Fau branches are independently optional in concrete realizations. Formate ligation/release is treated as one-carbon loading or unloading and is excluded with SHMT and glycine-cleavage input. Purine, thymidylate, and methionine synthesis are consumers and are also outside the module.
Connections
5,10-methenyl-THF produced by the dehydrogenase reaction is the cyclohydrolase substrate; the two activities are often fused but are chemically distinct.
Salvaged 5,10-methenyl-THF rejoins the methenyl/formyl carrier-state interconversion.
Part: Required core 5,10-methylene-THF and 5,10-methenyl-THF redox interconversion
5,10-methylene-THF to 5,10-methenyl-THF redoxReactionmethylene_methenyl_redox
Reversible pyridine-nucleotide-linked oxidation of 5,10-methylene-THF to 5,10-methenyl-THF. Organisms and compartments use NADP+- or NAD+-linked members of the FolD/MTHFD family.
Variant set: Pyridine-nucleotide-linked dehydrogenase variants by redox cofactor and enzyme architecture (Exactly One)
NADP-linked bifunctional FolD reactionReactionbacterial_fold_nadp_methylene_methenyl_variant
Annotons
Bacterial FolD NADP-linked dehydrogenase
bacterial_fold_nadp_methylene_methenyl_activity
Participant: Family: bifunctional FolD enzymes
Function
methylenetetrahydrofolate dehydrogenase (NADP+) activityGO:0004488 Bifunctional FolD implements the NADP-linked reaction together with the separately modeled cyclohydrolase activity in the same polypeptide.
NADP-linked monofunctional MtdA reactionReactionmonofunctional_mtda_nadp_methylene_methenyl_variant
Annotons
Monofunctional MtdA NADP-linked dehydrogenase
monofunctional_mtda_nadp_methylene_methenyl_activity
Participant: Ortholog Of: MtdA (Methylorubrum extorquens AM1)
Orthologs of experimentally characterized P55818 that retain its dual-carrier NADP-dependent dehydrogenase function; its two InterPro records describe domains and are not alternative family selectors.
Function
methylenetetrahydrofolate dehydrogenase (NADP+) activityGO:0004488 MtdA provides a monofunctional NADP-linked dehydrogenase architecture. It requires a separate cyclohydrolase such as FchA for the coupled core and primarily acts on H4MPT; only its experimentally observed THF reaction is in scope.
NADP-linked cytosolic MTHFD1 reactionReactioncytosolic_mthfd1_nadp_methylene_methenyl_variant
Annotons
Cytosolic MTHFD1 NADP-linked dehydrogenase
cytosolic_mthfd1_nadp_methylene_methenyl_activity
Participant: Family: eukaryotic cytosolic MTHFD1 enzymes
Function
methylenetetrahydrofolate dehydrogenase (NADP+) activityGO:0004488 Eukaryotic cytosolic MTHFD1 implements the same NADP-linked reaction in a larger multidomain C1-THF synthase.
NAD-linked MTHFD2 reactionReactionnad_methylene_methenyl_variant
Annotons
NAD-linked methylenetetrahydrofolate dehydrogenase
nad_methylene_methenyl_activity
Participant: Family: mitochondrial MTHFD2 enzymes
Function
methylenetetrahydrofolate dehydrogenase (NAD+) activityGO:0004487 Locations
Mitochondrial MTHFD2-family enzymes implement the NAD-linked version in metazoans and related lineages.
Part: Required core 5,10-methenyl-THF and 10-formyl-THF hydrolytic interconversion
Part: Optional 5,10-methylene-THF reduction to 5-methyl-THF branch (optional)
5,10-methylene-THF to 5-methyl-THF reductionReactionmethylene_methyl_reduction
FAD-dependent methylenetetrahydrofolate reductases use different pyridine-nucleotide cofactors in different enzyme architectures. Cofactor specificity is not inferred from organismal kingdom. The carrier-state product is modeled here; methionine synthase consumption of 5-methyl-THF is downstream.
Variant set: Methylenetetrahydrofolate reductase cofactor variants by pyridine-nucleotide specificity and enzyme architecture (Exactly One)
NADH-linked compact MetF reactionReactionnadh_mthfr_variant
Annotons
NADH-linked methylenetetrahydrofolate reductase
nadh_mthfr_activity
Participant: Family: compact bacterial MetF enzymes
Family:
compact bacterial MetF enzymesInterPro:IPR004620
Function
methylenetetrahydrofolate reductase (NADH) activityGO:0106312 Compact MetF proteins Q88D51 and P0AEZ1 exemplify this verified NADH-linked implementation; taxon alone is not a cofactor selector.
NADH-linked regulatory MTHFR reactionReactionregulatory_nadh_mthfr_variant
Annotons
Regulatory-architecture NADH methylenetetrahydrofolate reductase
regulatory_nadh_mthfr_activity
Participant: Ortholog Of: MTHFR2 (Arabidopsis thaliana)
Orthologs of experimentally characterized O80585 whose NADH dependence is established independently; the catalytic and SAM-binding InterPro domains specify architecture but not pyridine-nucleotide preference.
Function
methylenetetrahydrofolate reductase (NADH) activityGO:0106312 Arabidopsis O80585 demonstrates that an MTHFR with the eukaryotic catalytic and regulatory architecture can use NADH; neither cofactor nor architecture follows from kingdom alone.
NADPH-linked regulatory MTHFR reactionReactionnadph_mthfr_variant
Annotons
NADPH-linked methylenetetrahydrofolate reductase
nadph_mthfr_activity
Participant: Ortholog Of: MTHFR (human)
Orthologs of experimentally characterized P42898 whose NADPH dependence is established independently; broad MTHFR family and regulatory-domain records do not select this cofactor specificity.
Function
methylenetetrahydrofolate reductase (NADPH) activityGO:0106313 Human P42898 exemplifies an NADPH-linked implementation with a regulatory domain; this architecture is not used as a kingdom-wide cofactor rule.
Part: Optional 5-formyl-THF salvage to 5,10-methenyl-THF branch (optional)