Component

Methylcobalamin

Methylated cobalamin form participating in methionine synthase catalysis.

13 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. Melatonin rhythm amplitude before the light exposure was smaller during the B12 condition.

    Methylcobalamin → Amplitude of endogenous melatonin rhythm source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"}
    experimental_model
    Single-blind crossover light-response experiment
    exposure
    Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours
    limitations
    Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production.
    nutrient_topic
    Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
    organism
    Eight young men
    plain_language
    A lower amplitude and a shifted clock are separate measurements.
    primary_references
    [melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
    tissue_or_cell_type
    Circadian melatonin rhythm

    Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 812–823

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind crossover light-response experiment · source_derived_draft · unverified_draft

    ### melatonin-b12-amplitude Melatonin rhythm amplitude before the light exposure was smaller during the B12 condition. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower amplitude and a shifted clock are separate measurements. organism: Eight young men tissue_or_cell_type: Circadian melatonin rhythm experimental_model: Single-blind crossover light-response experiment limitations: Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production. exposure: Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours evidence_span: {"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"} [melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
    Complete structured claim and evidence

  2. The morning bright-light exposure advanced melatonin phase significantly during the B12 condition but not placebo.

    Methylcobalamin → Circadian phase shift after bright-light exposure source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"}
    experimental_model
    Single-blind crossover light-response experiment
    exposure
    Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours
    limitations
    Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production.
    nutrient_topic
    Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
    organism
    Eight young men
    plain_language
    A vitamin-related intervention affected timing of the signal rather than simply increasing its amount.
    primary_references
    [melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
    tissue_or_cell_type
    Circadian melatonin rhythm

    Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 799–810

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-blind crossover light-response experiment · source_derived_draft · unverified_draft

    ### melatonin-b12-phase-response The morning bright-light exposure advanced melatonin phase significantly during the B12 condition but not placebo. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin-related intervention affected timing of the signal rather than simply increasing its amount. organism: Eight young men tissue_or_cell_type: Circadian melatonin rhythm experimental_model: Single-blind crossover light-response experiment limitations: Small pharmacological B12 study, not B12-deficient participants. Does not establish a routine sleep treatment or increased melatonin production. exposure: Methylcobalamin IV 0.5 mg/day for 11 days then oral 6 mg/day for seven; morning 2500-lux light for three hours evidence_span: {"source_cache": "artifacts/melatonin-research/8981490.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792", "start_char": 0, "end_char": 895, "text_sha256": "d0079778f8efe44c1538b9c85d56b12a3a766b734aab19660419fd461ec22792"} [melatonin-p8981490] Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. (1996). https://pubmed.ncbi.nlm.nih.gov/8981490/ DOI: 10.1016/s0304-3940(96)13247-x
    Complete structured claim and evidence

  3. At 27 months, groups did not differ significantly in change in Clinical Dementia Rating or neuropsychological test z-scores.

    Methylcobalamin → Clinical Dementia Rating score source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    experimental_model
    Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L.
    exposure
    Oral methylcobalamin 1000 micrograms/day versus placebo for 27 months.
    limitations
    More smokers were randomized to active treatment; excluding smokers did not change the reported result.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Better markers did not establish protection from cognitive decline in this group.
    primary_references
    [b12-kwok2017] A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12 (2017). https://pubmed.ncbi.nlm.nih.gov/27823800/ DOI: 10.1016/j.clnu.2016.10.018
    tissue_or_cell_type
    Human blood or whole-person endpoints
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1573–1583

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L. · source_derived_draft · unverified_draft

    ### b12-methylcobalamin-diabetes-cognition At 27 months, groups did not differ significantly in change in Clinical Dementia Rating or neuropsychological test z-scores. Condition category: biomarker_context nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Better markers did not establish protection from cognitive decline in this group. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L. limitations: More smokers were randomized to active treatment; excluding smokers did not change the reported result. exposure: Oral methylcobalamin 1000 micrograms/day versus placebo for 27 months. [b12-kwok2017] A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12 (2017). https://pubmed.ncbi.nlm.nih.gov/27823800/ DOI: 10.1016/j.clnu.2016.10.018
    Complete structured claim and evidence

  4. MMA and homocysteine were significantly lower with methylcobalamin than placebo at months 9 and 27.

    Methylcobalamin → Methylmalonic acid source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    experimental_model
    Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L.
    exposure
    Oral methylcobalamin 1000 micrograms/day versus placebo for 27 months.
    limitations
    No direct cellular flux measurement and no head-to-head form comparison.
    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 B12 form improved the measured metabolic markers.
    primary_references
    [b12-kwok2017] A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12 (2017). https://pubmed.ncbi.nlm.nih.gov/27823800/ DOI: 10.1016/j.clnu.2016.10.018
    tissue_or_cell_type
    Human blood or whole-person endpoints
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1561–1571

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L. · source_derived_draft · unverified_draft

    ### b12-methylcobalamin-diabetes-metabolites MMA and homocysteine were significantly lower with methylcobalamin than placebo at months 9 and 27. Condition category: biomarker_context nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B12 form improved the measured metabolic markers. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Randomized placebo-controlled trial: 271 nondemented diabetic outpatients aged at least 70, plasma B12 150–300 pmol/L. limitations: No direct cellular flux measurement and no head-to-head form comparison. exposure: Oral methylcobalamin 1000 micrograms/day versus placebo for 27 months. [b12-kwok2017] A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12 (2017). https://pubmed.ncbi.nlm.nih.gov/27823800/ DOI: 10.1016/j.clnu.2016.10.018
    Complete structured claim and evidence

What acts on it

  1. Bovine aortic endothelial cells converted cobalt-57-labeled adenosylcobalamin into labeled methylcobalamin during metabolic labeling.

    5'-Deoxyadenosylcobalamin → Methylcobalamin source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Abstract; indexed Methods: Assessment of dealkylation; Discussion
    experimental_model
    Bovine aortic endothelial cell metabolic labeling
    exposure
    0.125 nM labeled alkylcobalamin; 48-hour processing assay protected from light
    limitations
    Cellular conversion supports processing but does not by itself identify every enzyme or establish a human supplement hierarchy.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Bos taurus
    plain_language
    These bovine cells could rework one active B12 form into the other.
    primary_references
    [hannibal-2009-cell-processing] Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product (2009). https://pubmed.ncbi.nlm.nih.gov/19447654/ DOI: 10.1016/j.ymgme.2009.04.005
    tissue_or_cell_type
    Aortic endothelium

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 795–807

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine aortic endothelial cell metabolic labeling · source_derived_draft · unverified_draft

    ### b12-bovine-ado-to-methyl Bovine aortic endothelial cells converted cobalt-57-labeled adenosylcobalamin into labeled methylcobalamin during metabolic labeling. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: These bovine cells could rework one active B12 form into the other. organism: Bos taurus tissue_or_cell_type: Aortic endothelium experimental_model: Bovine aortic endothelial cell metabolic labeling limitations: Cellular conversion supports processing but does not by itself identify every enzyme or establish a human supplement hierarchy. exposure: 0.125 nM labeled alkylcobalamin; 48-hour processing assay protected from light cross_nutrient: false evidence_location: Abstract; indexed Methods: Assessment of dealkylation; Discussion [hannibal-2009-cell-processing] Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product (2009). https://pubmed.ncbi.nlm.nih.gov/19447654/ DOI: 10.1016/j.ymgme.2009.04.005
    Complete structured claim and evidence

  2. Human MMACHC transfers the methyl group from methylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 11.7 +/- 0.2 per hour at 20 C.

    Human MMACHC / cobalamin-processing protein CblC → Methylcobalamin source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Primary abstract; indexed article Introduction/Figure 1
    experimental_model
    Purified human MMACHC substrate chemistry
    exposure
    Specified alkylcobalamin plus GSH; kinetic temperature 20 C
    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
    Glutathione receives the side group removed from this B12 form.
    primary_references
    [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
    tissue_or_cell_type
    Cell-free assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 711–723

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

    ### b12-mmachc-methyl-dealkylation Human MMACHC transfers the methyl group from methylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 11.7 +/- 0.2 per hour at 20 C. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione receives the side group removed from this B12 form. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC substrate chemistry limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: Specified alkylcobalamin plus GSH; kinetic temperature 20 C cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
    Complete structured claim and evidence

  3. MMADHC expression/translation-reinitiation experiments in cblD patient fibroblasts indicated that sequence after Met116 was sufficient to support methylcobalamin synthesis.

    Human MMADHC segment after Met116 → Methylcobalamin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Abstract
    experimental_model
    Human cblD fibroblast construct-rescue study
    exposure
    MMADHC constructs changing stop codons or downstream translation starts
    limitations
    Abstract-level domain inference; no claim of an independently purified physiological isoform.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    The later portion of MMADHC could support the methyl-B12 branch in these cells.
    primary_references
    [stucki-2012-mmad-routing] Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22156578/ DOI: 10.1093/hmg/ddr579
    tissue_or_cell_type
    Patient fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 851–863

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cblD fibroblast construct-rescue study · source_derived_draft · unverified_draft

    ### b12-mmad-after116-methyl MMADHC expression/translation-reinitiation experiments in cblD patient fibroblasts indicated that sequence after Met116 was sufficient to support methylcobalamin synthesis. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The later portion of MMADHC could support the methyl-B12 branch in these cells. organism: Homo sapiens tissue_or_cell_type: Patient fibroblasts experimental_model: Human cblD fibroblast construct-rescue study limitations: Abstract-level domain inference; no claim of an independently purified physiological isoform. exposure: MMADHC constructs changing stop codons or downstream translation starts cross_nutrient: false evidence_location: Abstract [stucki-2012-mmad-routing] Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22156578/ DOI: 10.1093/hmg/ddr579
    Complete structured claim and evidence

  4. In cblD-MMA/HC fibroblasts, an MMADHC construct with improved mitochondrial targeting decreased methylcobalamin formation relative to the targeting comparator.

    MMADHC with enhanced mitochondrial targeting sequence → Methylcobalamin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Abstract
    experimental_model
    Human cblD-MMA/HC fibroblast transfection
    exposure
    Engineered mitochondrial leader sequence
    limitations
    Abstract-level construct experiment; effect in isolated cblD-MMA lines depended on mutation and endogenous expression.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Redirecting MMADHC toward mitochondria decreased production of this B12 cofactor.
    primary_references
    [stucki-2012-mmad-routing] Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22156578/ DOI: 10.1093/hmg/ddr579
    tissue_or_cell_type
    Patient fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 837–849

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cblD-MMA/HC fibroblast transfection · source_derived_draft · unverified_draft

    ### b12-mmad-mito-target-methylcobalamin In cblD-MMA/HC fibroblasts, an MMADHC construct with improved mitochondrial targeting decreased methylcobalamin formation relative to the targeting comparator. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Redirecting MMADHC toward mitochondria decreased production of this B12 cofactor. organism: Homo sapiens tissue_or_cell_type: Patient fibroblasts experimental_model: Human cblD-MMA/HC fibroblast transfection limitations: Abstract-level construct experiment; effect in isolated cblD-MMA lines depended on mutation and endogenous expression. exposure: Engineered mitochondrial leader sequence cross_nutrient: false evidence_location: Abstract [stucki-2012-mmad-routing] Molecular mechanisms leading to three different phenotypes in the cblD defect of intracellular cobalamin metabolism (2012). https://pubmed.ncbi.nlm.nih.gov/22156578/ DOI: 10.1093/hmg/ddr579
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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

  2. Fibroblasts from three cblC patients had little or no conversion of cobalt-57-labeled propylcobalamin into adenosylcobalamin and methylcobalamin, whereas control skin fibroblasts converted the probe.

    Human MMACHC gene → Propylcobalamin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Abstract; indexed Methods: Assessment of dealkylation; Discussion
    experimental_model
    Human control and cblC patient fibroblast labeling
    exposure
    0.125 nM cobalt-57 propylcobalamin for 48 hours
    limitations
    Propylcobalamin is a synthetic C3 probe; patients and genotypes differ and this comparison does not quantify every natural vitamer response.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    A synthetic B12 probe exposed the processing defect in patient cells.
    primary_references
    [hannibal-2009-cell-processing] Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product (2009). https://pubmed.ncbi.nlm.nih.gov/19447654/ DOI: 10.1016/j.ymgme.2009.04.005
    tissue_or_cell_type
    Skin fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 809–821

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human control and cblC patient fibroblast labeling · source_derived_draft · unverified_draft

    ### b12-cblc-propyl-probe Fibroblasts from three cblC patients had little or no conversion of cobalt-57-labeled propylcobalamin into adenosylcobalamin and methylcobalamin, whereas control skin fibroblasts converted the probe. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A synthetic B12 probe exposed the processing defect in patient cells. organism: Homo sapiens tissue_or_cell_type: Skin fibroblasts experimental_model: Human control and cblC patient fibroblast labeling limitations: Propylcobalamin is a synthetic C3 probe; patients and genotypes differ and this comparison does not quantify every natural vitamer response. exposure: 0.125 nM cobalt-57 propylcobalamin for 48 hours cross_nutrient: false evidence_location: Abstract; indexed Methods: Assessment of dealkylation; Discussion [hannibal-2009-cell-processing] Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product (2009). https://pubmed.ncbi.nlm.nih.gov/19447654/ DOI: 10.1016/j.ymgme.2009.04.005
    Complete structured claim and evidence

  3. Human MMADHC delta123 carrying T182N showed strongly reduced complex formation with full-length human MMACHC after MeCbl/GSH incubation, compared with matched delta123 MMADHC.

    Human MMADHC delta123 T182N → Human MMACHC / cobalamin-processing protein CblC source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Results: Figure 5D; Experimental Procedures
    experimental_model
    Recombinant human proteins; blue-native PAGE
    exposure
    T182N versus matched delta123 comparator, MMACHC, MeCbl and GSH
    limitations
    Functional assay used human proteins; mouse MMADHC was used for the separate crystal structure. Truncation may affect full-length behavior.
    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 variant disrupted the two processing proteins’ association.
    primary_references
    [froese-2015-complex] Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking (2015). https://pubmed.ncbi.nlm.nih.gov/26483544/ DOI: 10.1074/jbc.M115.683268
    tissue_or_cell_type
    Cell-free assay
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 865–877

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

    ### b12-mmad-t182n-complex Human MMADHC delta123 carrying T182N showed strongly reduced complex formation with full-length human MMACHC after MeCbl/GSH incubation, compared with matched delta123 MMADHC. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant disrupted the two processing proteins’ association. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Recombinant human proteins; blue-native PAGE limitations: Functional assay used human proteins; mouse MMADHC was used for the separate crystal structure. Truncation may affect full-length behavior. exposure: T182N versus matched delta123 comparator, MMACHC, MeCbl and GSH cross_nutrient: false evidence_location: Results: Figure 5D; Experimental Procedures [froese-2015-complex] Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking (2015). https://pubmed.ncbi.nlm.nih.gov/26483544/ DOI: 10.1074/jbc.M115.683268
    Complete structured claim and evidence

  4. Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF.

    Cobalamin-dependent methionine synthase / MTR → L-Methionine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Folate methyl transfer requires B12.
    experimental_model
    Human MTR/MTRR expressed in insect cells; purified enzymes and extracts.
    limitations
    Chemistry, not dietary response.
    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
    B12-dependent MTR recycles both homocysteine and folate.
    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 protein

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 482–492

    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-mtr-methyl-transfer Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: B12-dependent MTR recycles both homocysteine and folate. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. limitations: Chemistry, not dietary response. cross_nutrient: Folate methyl transfer requires B12. [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

  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

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