Component

Methionine synthase reductase / MTRR

Dual-flavin reductase supporting reactivation of methionine synthase.

8 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Purified recombinant human MTRR contained equimolar FAD and FMN, identifying two distinct flavin cofactors in the same reductase.

    Methionine synthase reductase / MTRR → FAD source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B2-derived flavins form part of the B12-reactivation machinery.
    evidence_location
    Abstract
    experimental_model
    Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
    exposure
    Purified-enzyme assay
    limitations
    Biochemical evidence does not establish a dietary threshold or supplementation benefit.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    MTRR uses both B2-derived cofactors.
    primary_references
    [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
    tissue_or_cell_type
    Purified recombinant enzyme; no intact tissue

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1094–1106

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft

    ### b2-mtrr-dual-flavins Purified recombinant human MTRR contained equimolar FAD and FMN, identifying two distinct flavin cofactors in the same reductase. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: MTRR uses both B2-derived cofactors. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-derived flavins form part of the B12-reactivation machinery. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
    Complete structured claim and evidence

  2. Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase.

    Methionine synthase reductase / MTRR → Cobalamin-dependent methionine synthase / MTR source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism.
    evidence_location
    Abstract
    experimental_model
    Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
    exposure
    Purified-enzyme assay
    limitations
    Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    The flavin reductase helps restore an enzyme that uses B12 and methylfolate.
    primary_references
    [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
    tissue_or_cell_type
    Purified recombinant enzyme; no intact tissue

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1122–1134

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft

    ### b2-mtrr-mtr-reactivation Reconstituted assays showed human MTRR sufficient to support NADPH-dependent activity of cobalamin-dependent methionine synthase. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin reductase helps restore an enzyme that uses B12 and methylfolate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Reconstituted biochemistry; the accessible abstract identifies human MTRR but not the target MTR species. No dietary B2/B12 synergy was tested. exposure: Purified-enzyme assay cross_nutrient: B2 flavins support reactivation of B12-dependent folate/homocysteine metabolism. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
    Complete structured claim and evidence

  3. Recombinant human MTRR with NADPH supported MMACHC-bound cyanocobalamin conversion to cob(II)alamin; free cyanocobalamin was not detectably reduced without MMACHC.

    Methionine synthase reductase / MTRR → Human MMACHC / cobalamin-processing protein CblC source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Results: Figure 4; Materials and Methods: Decyanation of CNCbl
    experimental_model
    Human purified-protein anaerobic reconstitution
    exposure
    4 micromolar reductase, 20 micromolar MMACHC/CNCbl, 200 micromolar NADPH
    limitations
    Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    This flavoprotein can pass reducing power into B12 processing.
    primary_references
    [kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
    tissue_or_cell_type
    Cell-free assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 683–695

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human purified-protein anaerobic reconstitution · source_derived_draft · unverified_draft

    ### b12-mtrr-mmachc-electrons Recombinant human MTRR with NADPH supported MMACHC-bound cyanocobalamin conversion to cob(II)alamin; free cyanocobalamin was not detectably reduced without MMACHC. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This flavoprotein can pass reducing power into B12 processing. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Human purified-protein anaerobic reconstitution limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: 4 micromolar reductase, 20 micromolar MMACHC/CNCbl, 200 micromolar NADPH cross_nutrient: true evidence_location: Results: Figure 4; Materials and Methods: Decyanation of CNCbl [kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
    Complete structured claim and evidence

  4. Purified human MTRR coupled cob(II)alamin reduction to MMAB-dependent adenosylcobalamin synthesis in vitro.

    Methionine synthase reductase / MTRR → Human ATP:cob(I)alamin adenosyltransferase / MMAB source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Indexed primary abstract
    experimental_model
    Purified human proteins
    exposure
    Purified MTRR plus MMAB and reductants
    limitations
    MTRR coupling in vitro does not identify the physiological mitochondrial electron donor.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Human MTRR supported B12 activation in a test-tube system; this does not establish its mitochondrial role.
    primary_references
    [leal-2004-human-mmab] Human ATP:Cob(I)alamin adenosyltransferase and its interaction with methionine synthase reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/15347655/ DOI: 10.1074/jbc.m405449200
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 991–1003

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human proteins · source_derived_draft · unverified_draft

    ### mtrr-supports-mmab-in-vitro Purified human MTRR coupled cob(II)alamin reduction to MMAB-dependent adenosylcobalamin synthesis in vitro. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human MTRR supported B12 activation in a test-tube system; this does not establish its mitochondrial role. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: MTRR coupling in vitro does not identify the physiological mitochondrial electron donor. exposure: Purified MTRR plus MMAB and reductants cross_nutrient: true evidence_location: Indexed primary abstract [leal-2004-human-mmab] Human ATP:Cob(I)alamin adenosyltransferase and its interaction with methionine synthase reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/15347655/ DOI: 10.1074/jbc.m405449200
    Complete structured claim and evidence

  5. Human MTRR stabilized apo-MTR and enhanced holoenzyme formation from methylcobalamin in the presence of NADPH.

    Methionine synthase reductase / MTRR → Cobalamin-dependent methionine synthase / MTR source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Flavin-dependent MTRR supports B12-enzyme assembly.
    experimental_model
    Human MTR/MTRR expressed in insect cells; purified enzymes and extracts.
    limitations
    In-vitro assembly.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    MTRR also helps MTR acquire its cofactor.
    primary_references
    [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
    tissue_or_cell_type
    Human proteins expressed in insect cells

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 494–504

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. · source_derived_draft · unverified_draft

    ### folate-methyl-mtrr-apoenzyme Human MTRR stabilized apo-MTR and enhanced holoenzyme formation from methylcobalamin in the presence of NADPH. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: MTRR also helps MTR acquire its cofactor. organism: Homo sapiens tissue_or_cell_type: Human proteins expressed in insect cells experimental_model: Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. limitations: In-vitro assembly. cross_nutrient: Flavin-dependent MTRR supports B12-enzyme assembly. [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
    Complete structured claim and evidence

  6. Human MTRR sustained human MTR, whereas bacterial flavodoxin/flavodoxin reductase did not significantly support the human enzyme.

    Methionine synthase reductase / MTRR → Cobalamin-dependent methionine synthase / MTR source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human MTR/MTRR expressed in insect cells; purified enzymes and extracts.
    limitations
    Bacterial proteins are assay comparators.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    The electron-donor partners were species selective.
    primary_references
    [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
    tissue_or_cell_type
    Purified proteins

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 506–515

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. · source_derived_draft · unverified_draft

    ### folate-methyl-mtrr-species-recognition Human MTRR sustained human MTR, whereas bacterial flavodoxin/flavodoxin reductase did not significantly support the human enzyme. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The electron-donor partners were species selective. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. limitations: Bacterial proteins are assay comparators. [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
    Complete structured claim and evidence

What acts on it

  1. NADPH reduction of purified MTRR generated an air-stable flavin semiquinone detected spectroscopically.

    NADPH → Methionine synthase reductase / MTRR source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Nicotinamide-containing NADPH supplies electrons to B2-derived flavins.
    evidence_location
    Abstract
    experimental_model
    Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution.
    exposure
    Purified-enzyme assay
    limitations
    Biochemical evidence does not establish a dietary threshold or supplementation benefit.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    NADPH provides electrons to the flavin-containing reductase.
    primary_references
    [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
    tissue_or_cell_type
    Purified recombinant enzyme; no intact tissue

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1108–1120

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. · source_derived_draft · unverified_draft

    ### b2-mtrr-nadph-reduction NADPH reduction of purified MTRR generated an air-stable flavin semiquinone detected spectroscopically. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NADPH provides electrons to the flavin-containing reductase. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human MTRR purification, flavin analysis, NADPH spectroscopy and methionine-synthase reconstitution. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: Nicotinamide-containing NADPH supplies electrons to B2-derived flavins. evidence_location: Abstract [olteanu2001] Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. (2001). https://pubmed.ncbi.nlm.nih.gov/11466310/ DOI: 10.1074/jbc.m103707200
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Human MMACHC converted bound cyanocobalamin to cob(II)alamin during NADPH-supported reductive decyanation; EPR identified the product in a base-off coordination state.

    Human MMACHC / cobalamin-processing protein CblC → Cyanocobalamin source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Results: Figure 4; Materials and Methods: Decyanation of CNCbl
    experimental_model
    Purified human MMACHC with human flavoprotein donor
    exposure
    Anaerobic CNCbl/MMACHC, NADPH and MTRR or NDOR1
    limitations
    Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Processing removes the cyano group and leaves a reduced B12 intermediate.
    primary_references
    [kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
    tissue_or_cell_type
    Cell-free assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 669–681

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC with human flavoprotein donor · source_derived_draft · unverified_draft

    ### b12-mmachc-decyanation Human MMACHC converted bound cyanocobalamin to cob(II)alamin during NADPH-supported reductive decyanation; EPR identified the product in a base-off coordination state. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Processing removes the cyano group and leaves a reduced B12 intermediate. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC with human flavoprotein donor limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: Anaerobic CNCbl/MMACHC, NADPH and MTRR or NDOR1 cross_nutrient: true evidence_location: Results: Figure 4; Materials and Methods: Decyanation of CNCbl [kim-2008-decyanation] Decyanation of vitamin B12 by a trafficking chaperone (2008). https://pubmed.ncbi.nlm.nih.gov/18779575/ DOI: 10.1073/pnas.0805989105
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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