Component

Human methylmalonyl-CoA mutase / MMUT

Human methylmalonyl-CoA mutase / MMUT

14 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. Adenosylcobalamin-loaded human MMUT converts (R)-methylmalonyl-CoA to succinyl-CoA in the coupled enzyme assay.

    Human methylmalonyl-CoA mutase / MMUT → (R)-Methylmalonyl-CoA source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods
    experimental_model
    Purified human proteins
    exposure
    AdoCbl-loaded MMUT and methylmalonyl-CoA; thiokinase-coupled readout
    limitations
    Product formation is a coupled assay; cellular net flux was not measured.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Purified human MMUT used activated B12 to make succinyl-CoA from the matching methylmalonyl-CoA epimer.
    primary_references
    [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1103–1115

    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

    ### mmut-isomerizes-r-methylmalonyl-coa Adenosylcobalamin-loaded human MMUT converts (R)-methylmalonyl-CoA to succinyl-CoA in the coupled enzyme assay. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Purified human MMUT used activated B12 to make succinyl-CoA from the matching methylmalonyl-CoA epimer. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Product formation is a coupled assay; cellular net flux was not measured. exposure: AdoCbl-loaded MMUT and methylmalonyl-CoA; thiokinase-coupled readout cross_nutrient: false evidence_location: Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
    Complete structured claim and evidence

What acts on it

  1. Itaconyl-CoA inactivated purified human MMUT by forming a stable adduct with the B12-derived deoxyadenosyl moiety.

    Itaconyl-CoA → Human methylmalonyl-CoA mutase / MMUT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Primary abstract; indexed Results and Figure 3E
    experimental_model
    Purified human MMUT; inhibitor-product spectroscopy and analysis
    exposure
    Itaconyl-CoA exposure in the purified-enzyme assay
    limitations
    Mechanism-based inhibitor is distinct from physiological methylmalonyl-CoA; no human dietary effect inferred.
    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 itaconyl-CoA experiment trapped B12 radical chemistry and stopped the purified human enzyme.
    primary_references
    [ruetz-2019-itaconyl-radical] Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. (2019). https://pubmed.ncbi.nlm.nih.gov/31672889/ DOI: 10.1126/science.aay0934
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1384–1396

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

    ### itaconyl-coa-inactivates-human-mmut Itaconyl-CoA inactivated purified human MMUT by forming a stable adduct with the B12-derived deoxyadenosyl moiety. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The itaconyl-CoA experiment trapped B12 radical chemistry and stopped the purified human enzyme. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human MMUT; inhibitor-product spectroscopy and analysis limitations: Mechanism-based inhibitor is distinct from physiological methylmalonyl-CoA; no human dietary effect inferred. exposure: Itaconyl-CoA exposure in the purified-enzyme assay cross_nutrient: false evidence_location: Primary abstract; indexed Results and Figure 3E [ruetz-2019-itaconyl-radical] Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. (2019). https://pubmed.ncbi.nlm.nih.gov/31672889/ DOI: 10.1126/science.aay0934
    Complete structured claim and evidence

  2. Human MMAA G188R retained basal GTPase activity but lost the detected MMUT interaction.

    Human MMAA p.Gly188Arg → Human methylmalonyl-CoA mutase / MMUT source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Indexed primary abstract; indexed Results
    experimental_model
    Human MMAA G188R functional assays
    exposure
    G188R patient variant versus wild type
    limitations
    Interaction defect in experimental assays; residual tissue-specific function was not quantified.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    In the human-protein experiment, this MMAA variant still hydrolyzed GTP but failed to bind MMUT normally.
    primary_references
    [froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717
    tissue_or_cell_type
    Purified protein assay
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1061–1073

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MMAA G188R functional assays · source_derived_draft · unverified_draft

    ### mmaa-g188r-loses-mmut-interaction Human MMAA G188R retained basal GTPase activity but lost the detected MMUT interaction. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In the human-protein experiment, this MMAA variant still hydrolyzed GTP but failed to bind MMUT normally. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Human MMAA G188R functional assays limitations: Interaction defect in experimental assays; residual tissue-specific function was not quantified. exposure: G188R patient variant versus wild type cross_nutrient: false evidence_location: Indexed primary abstract; indexed Results [froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717
    Complete structured claim and evidence

  3. Human MMAA formed a stable complex preferentially with apo-MMUT and with GMPPNP rather than GDP.

    Human MMAA GTPase → Human methylmalonyl-CoA mutase / MMUT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Indexed primary abstract; indexed Results
    experimental_model
    Purified human proteins
    exposure
    Apo versus holo-MMUT; GMPPNP versus GDP
    limitations
    GMPPNP is a GTP analogue; stable-complex abundance is not cofactor transfer rate.
    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 purified human proteins assembled differently depending on MMUT cofactor occupancy and nucleotide state.
    primary_references
    [froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1047–1059

    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

    ### mmaa-prefers-apo-mmut-complex Human MMAA formed a stable complex preferentially with apo-MMUT and with GMPPNP rather than GDP. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The purified human proteins assembled differently depending on MMUT cofactor occupancy and nucleotide state. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: GMPPNP is a GTP analogue; stable-complex abundance is not cofactor transfer rate. exposure: Apo versus holo-MMUT; GMPPNP versus GDP cross_nutrient: false evidence_location: Indexed primary abstract; indexed Results [froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717
    Complete structured claim and evidence

  4. Adding human MMAA at reaction initiation protected recombinant human MMUT against catalytic inactivation.

    Human MMAA GTPase → Human methylmalonyl-CoA mutase / MMUT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Indexed primary abstract
    experimental_model
    Purified human proteins
    exposure
    MMAA added at reaction initiation
    limitations
    Biochemical reconstitution; does not determine cellular rate or dietary requirement.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    MMAA helped purified human MMUT remain active during the tested reaction.
    primary_references
    [takahashi-2010-mmaa-repair] Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein. (2011). https://pubmed.ncbi.nlm.nih.gov/21138732/ DOI: 10.1016/j.bbrc.2010.11.141
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1075–1087

    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

    ### mmaa-protects-mmut-activity Adding human MMAA at reaction initiation protected recombinant human MMUT against catalytic inactivation. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: MMAA helped purified human MMUT remain active during the tested reaction. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Biochemical reconstitution; does not determine cellular rate or dietary requirement. exposure: MMAA added at reaction initiation cross_nutrient: false evidence_location: Indexed primary abstract [takahashi-2010-mmaa-repair] Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein. (2011). https://pubmed.ncbi.nlm.nih.gov/21138732/ DOI: 10.1016/j.bbrc.2010.11.141
    Complete structured claim and evidence

  5. Adding MMAA after 60 minutes restored activity in an inactivated human MMUT reaction through GTP hydrolysis.

    Human MMAA GTPase → Human methylmalonyl-CoA mutase / MMUT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Indexed primary abstract
    experimental_model
    Purified human proteins
    exposure
    MMAA added after 60-minute catalytic inactivation
    limitations
    In-vitro reactivation; abstract interprets damaged-cofactor exchange rather than measuring every intermediate.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    MMAA restarted an inactive purified human MMUT reaction in a GTP-dependent assay.
    primary_references
    [takahashi-2010-mmaa-repair] Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein. (2011). https://pubmed.ncbi.nlm.nih.gov/21138732/ DOI: 10.1016/j.bbrc.2010.11.141
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1089–1101

    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

    ### mmaa-reactivates-mmut Adding MMAA after 60 minutes restored activity in an inactivated human MMUT reaction through GTP hydrolysis. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: MMAA restarted an inactive purified human MMUT reaction in a GTP-dependent assay. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: In-vitro reactivation; abstract interprets damaged-cofactor exchange rather than measuring every intermediate. exposure: MMAA added after 60-minute catalytic inactivation cross_nutrient: false evidence_location: Indexed primary abstract [takahashi-2010-mmaa-repair] Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein. (2011). https://pubmed.ncbi.nlm.nih.gov/21138732/ DOI: 10.1016/j.bbrc.2010.11.141
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. ADP binding protected cob(II)alamin on human MMUT from air oxidation by stabilizing a solvent-shielded conformation.

    Adenosine diphosphate → Overoxidation of human MMUT-bound cob(II)alamin source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Full text Results; Figures 2-3, Table 3
    experimental_model
    Purified human proteins
    exposure
    ADP added to MMUT-bound cob(II)alamin under air
    limitations
    Structural/biochemical protection does not establish regulation by cellular energy charge.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    ADP helped preserve an inactive B12 cofactor for repair in the human-protein assay.
    primary_references
    [gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1398–1410

    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

    ### adp-protects-mmut-cofactor-redox ADP binding protected cob(II)alamin on human MMUT from air oxidation by stabilizing a solvent-shielded conformation. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: ADP helped preserve an inactive B12 cofactor for repair in the human-protein assay. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Structural/biochemical protection does not establish regulation by cellular energy charge. exposure: ADP added to MMUT-bound cob(II)alamin under air cross_nutrient: false evidence_location: Full text Results; Figures 2-3, Table 3 [gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120
    Complete structured claim and evidence

  2. Under anaerobic conditions, ADP reduced the rate of cob(II)alamin transfer from human MMUT to MMAB in the MMAA repair system.

    Adenosine diphosphate → Cob(II)alamin off-loading from human MMUT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Full text Results; Figures 2-3, Table 3
    experimental_model
    Purified human proteins
    exposure
    Anaerobic cofactor-transfer assay with ADP
    limitations
    Transfer rate differs from oxidation protection; methylmalonyl-CoA reversed ADP inhibition in this assay.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    When oxidation was excluded, ADP slowed transfer of inactive B12 between the purified human proteins.
    primary_references
    [gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1412–1424

    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

    ### adp-slows-mmut-cob-ii-offloading Under anaerobic conditions, ADP reduced the rate of cob(II)alamin transfer from human MMUT to MMAB in the MMAA repair system. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: When oxidation was excluded, ADP slowed transfer of inactive B12 between the purified human proteins. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Transfer rate differs from oxidation protection; methylmalonyl-CoA reversed ADP inhibition in this assay. exposure: Anaerobic cofactor-transfer assay with ADP cross_nutrient: false evidence_location: Full text Results; Figures 2-3, Table 3 [gouda-2023-adp-repair] Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair. (2023). https://pubmed.ncbi.nlm.nih.gov/36888659/ DOI: 10.1073/pnas.2220677120
    Complete structured claim and evidence

  3. Human MCEE interconverts methylmalonyl-CoA epimers, supplying the (R) form for MMUT; MCEE expression increased coupled succinate production.

    Human methylmalonyl-CoA epimerase / MCEE → (S)-Methylmalonyl-CoA source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Full text Methods 2.6 and Results 3.6; Figure 5
    experimental_model
    Human fibroblast lysates overexpressing MCEE and/or MMUT
    exposure
    Radiolabeled propionyl-CoA; MCEE/MMUT expression and AdoCbl
    limitations
    Coupled labeled hydrolysis-product assay; MCEE being limiting here is not a universal in-vivo rate limitation.
    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 fibroblast assays showed why the epimerase step matters before the B12 enzyme.
    primary_references
    [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
    tissue_or_cell_type
    Fibroblasts

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1174–1186

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human fibroblast lysates overexpressing MCEE and/or MMUT · source_derived_draft · unverified_draft

    ### mcee-epimerizes-methylmalonyl-coa Human MCEE interconverts methylmalonyl-CoA epimers, supplying the (R) form for MMUT; MCEE expression increased coupled succinate production. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human fibroblast assays showed why the epimerase step matters before the B12 enzyme. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Human fibroblast lysates overexpressing MCEE and/or MMUT limitations: Coupled labeled hydrolysis-product assay; MCEE being limiting here is not a universal in-vivo rate limitation. exposure: Radiolabeled propionyl-CoA; MCEE/MMUT expression and AdoCbl cross_nutrient: false evidence_location: Full text Methods 2.6 and Results 3.6; Figure 5 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
    Complete structured claim and evidence

  4. Human MCEE I53R lacked measured activity in the coupled patient-fibroblast assay with overexpressed MMUT and added adenosylcobalamin.

    Human MCEE p.Ile53Arg → Human MCEE-dependent coupled propionyl-CoA pathway activity source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Full text Methods 2.6 and Results 3.6; Figure 5
    experimental_model
    MCEE-null human fibroblasts expressing MCEE I53R
    exposure
    I53R expression; MMUT coexpression; 50 micromolar AdoCbl
    limitations
    Overexpression assay; not a clinical test of B12 treatment.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Adding activated B12 did not make this defective epimerase work in the human-cell assay.
    primary_references
    [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
    tissue_or_cell_type
    Fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1188–1200

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · MCEE-null human fibroblasts expressing MCEE I53R · source_derived_draft · unverified_draft

    ### mcee-i53r-reduces-coupled-activity Human MCEE I53R lacked measured activity in the coupled patient-fibroblast assay with overexpressed MMUT and added adenosylcobalamin. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding activated B12 did not make this defective epimerase work in the human-cell assay. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: MCEE-null human fibroblasts expressing MCEE I53R limitations: Overexpression assay; not a clinical test of B12 treatment. exposure: I53R expression; MMUT coexpression; 50 micromolar AdoCbl cross_nutrient: false evidence_location: Full text Methods 2.6 and Results 3.6; Figure 5 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
    Complete structured claim and evidence

  5. The human MMUT-MMAA structure showed MMAA stabilizing a roughly 180-degree rotation that exposed the MMUT B12-binding domain.

    Human MMAA GTPase → Exposure of the human MMUT cobalamin-binding domain source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods
    experimental_model
    Purified human proteins
    exposure
    Crystallized complex with CoA, GDP and Mg2+
    limitations
    Static structure; does not directly measure the complete loading trajectory.
    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 human-protein structure showed how MMAA opens access to MMUT-bound B12.
    primary_references
    [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129

    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

    ### mmaa-exposes-mmut-cobalamin-domain The human MMUT-MMAA structure showed MMAA stabilizing a roughly 180-degree rotation that exposed the MMUT B12-binding domain. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human-protein structure showed how MMAA opens access to MMUT-bound B12. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Static structure; does not directly measure the complete loading trajectory. exposure: Crystallized complex with CoA, GDP and Mg2+ cross_nutrient: false evidence_location: Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
    Complete structured claim and evidence

  6. Purified human MMAA displayed intrinsic GTPase activity modulated by human MMUT.

    Human MMAA GTPase → Guanosine triphosphate source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Indexed primary abstract; indexed Results
    experimental_model
    Purified human proteins
    exposure
    GTP hydrolysis assay
    limitations
    Biochemical reconstitution; does not determine cellular rate or dietary requirement.
    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 MMAA consumed GTP in the protein assay, linking energy use to B12 handling.
    primary_references
    [froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1033–1045

    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

    ### mmaa-hydrolyzes-gtp Purified human MMAA displayed intrinsic GTPase activity modulated by human MMUT. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human MMAA consumed GTP in the protein assay, linking energy use to B12 handling. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Biochemical reconstitution; does not determine cellular rate or dietary requirement. exposure: GTP hydrolysis assay cross_nutrient: false evidence_location: Indexed primary abstract; indexed Results [froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717
    Complete structured claim and evidence

  7. A human MMAA/MMAB repair mixture with GTP and ATP transferred cob(II)alamin from MMUT to MMAB in anaerobic spectroscopy.

    Human MMAA GTPase → Cob(II)alamin off-loading from human MMUT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods
    experimental_model
    Purified human proteins
    exposure
    Anaerobic assay; MMAB, MMAA, GTP and ATP
    limitations
    Reconstituted transfer; spectroscopy reports cofactor environment, not cellular turnover.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    In the purified repair assay, inactive B12 moved from MMUT back to MMAB.
    primary_references
    [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
    tissue_or_cell_type
    Purified protein assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1131–1143

    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

    ### mmaa-mmab-offload-cob-ii A human MMAA/MMAB repair mixture with GTP and ATP transferred cob(II)alamin from MMUT to MMAB in anaerobic spectroscopy. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In the purified repair assay, inactive B12 moved from MMUT back to MMAB. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Reconstituted transfer; spectroscopy reports cofactor environment, not cellular turnover. exposure: Anaerobic assay; MMAB, MMAA, GTP and ATP cross_nutrient: false evidence_location: Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4
    Complete structured claim and evidence

  8. Human PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays.

    Human propionyl-CoA carboxylase / PCC → Propionyl-CoA source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5
    experimental_model
    Human fibroblast PCC and coupled-pathway assays
    exposure
    Propionyl-CoA, ATP and bicarbonate in enzyme pathway
    limitations
    Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it.
    primary_references
    [hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
    tissue_or_cell_type
    Fibroblasts

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1159–1172

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human fibroblast PCC and coupled-pathway assays · source_derived_draft · unverified_draft

    ### pcc-carboxylation-upstream-b12 Human PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Human fibroblast PCC and coupled-pathway assays limitations: Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention. exposure: Propionyl-CoA, ATP and bicarbonate in enzyme pathway cross_nutrient: true evidence_location: Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5 [hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021
    Complete structured claim and evidence

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    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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