Component

Human MMADHC / cobalamin-trafficking protein CblD

Human MMADHC / cobalamin-trafficking protein CblD

5 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. Human MMADHC donated the Cys261 sulfur ligand to MMACHC-bound cob(II)alamin, forming an interprotein complex that oxidized to thiolato-cob(III)alamin.

    Human MMADHC / cobalamin-trafficking protein CblD → Human MMACHC / cobalamin-processing protein CblC source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Abstract; indexed Results: CblD binds H2OCbl and forms a complex with CblC
    experimental_model
    Human recombinant chaperones; cysteine scanning and EPR/X-ray absorption
    exposure
    MMACHC-bound cob(II)alamin mixed with MMADHC; oxygen controls
    limitations
    Chemical complex formation does not alone prove the complete in-cell route from lysosome to either client enzyme.
    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 sulfur atom on one chaperone helped hold B12 while it remained bound to the other.
    primary_references
    [li-2020-co-s] An Interprotein Co-S Coordination Complex in the B12-Trafficking Pathway (2020). https://pubmed.ncbi.nlm.nih.gov/32871076/ DOI: 10.1021/jacs.0c06590
    tissue_or_cell_type
    Cell-free assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 879–891

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant chaperones; cysteine scanning and EPR/X-ray absorption · source_derived_draft · unverified_draft

    ### b12-mmad-cys261-co-s Human MMADHC donated the Cys261 sulfur ligand to MMACHC-bound cob(II)alamin, forming an interprotein complex that oxidized to thiolato-cob(III)alamin. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sulfur atom on one chaperone helped hold B12 while it remained bound to the other. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Human recombinant chaperones; cysteine scanning and EPR/X-ray absorption limitations: Chemical complex formation does not alone prove the complete in-cell route from lysosome to either client enzyme. exposure: MMACHC-bound cob(II)alamin mixed with MMADHC; oxygen controls cross_nutrient: false evidence_location: Abstract; indexed Results: CblD binds H2OCbl and forms a complex with CblC [li-2020-co-s] An Interprotein Co-S Coordination Complex in the B12-Trafficking Pathway (2020). https://pubmed.ncbi.nlm.nih.gov/32871076/ DOI: 10.1021/jacs.0c06590
    Complete structured claim and evidence

  2. Reduced, full-length human MMADHC bound free aquocobalamin in vitro with a reported KD of 1.0 +/- 0.4 micromolar and formed a base-on thiolato-cob(III)alamin species.

    Human MMADHC / cobalamin-trafficking protein CblD → Aquocobalamin source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Abstract; indexed Results: CblD binds H2OCbl and forms a complex with CblC
    experimental_model
    Human full-length recombinant MMADHC binding assay
    exposure
    Reduction of cysteines followed by removal of excess DTT; free aquocobalamin
    limitations
    Slow binding and micromolar affinity make free aquocobalamin capture an uncertain physiological route; older no-binding results were condition-sensitive.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    MMADHC could bind this B12 form directly under the preparation conditions.
    primary_references
    [li-2020-co-s] An Interprotein Co-S Coordination Complex in the B12-Trafficking Pathway (2020). https://pubmed.ncbi.nlm.nih.gov/32871076/ DOI: 10.1021/jacs.0c06590
    tissue_or_cell_type
    Cell-free assay

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 893–905

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human full-length recombinant MMADHC binding assay · source_derived_draft · unverified_draft

    ### b12-mmad-free-aquo-binding Reduced, full-length human MMADHC bound free aquocobalamin in vitro with a reported KD of 1.0 +/- 0.4 micromolar and formed a base-on thiolato-cob(III)alamin species. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: MMADHC could bind this B12 form directly under the preparation conditions. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Human full-length recombinant MMADHC binding assay limitations: Slow binding and micromolar affinity make free aquocobalamin capture an uncertain physiological route; older no-binding results were condition-sensitive. exposure: Reduction of cysteines followed by removal of excess DTT; free aquocobalamin cross_nutrient: false evidence_location: Abstract; indexed Results: CblD binds H2OCbl and forms a complex with CblC [li-2020-co-s] An Interprotein Co-S Coordination Complex in the B12-Trafficking Pathway (2020). https://pubmed.ncbi.nlm.nih.gov/32871076/ DOI: 10.1021/jacs.0c06590
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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

  2. In cblD-MMA/HC fibroblasts, an MMADHC construct with improved mitochondrial targeting increased adenosylcobalamin formation relative to the targeting comparator.

    MMADHC with enhanced mitochondrial targeting sequence → 5'-Deoxyadenosylcobalamin 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 increased 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 823–835

    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-adenosylcobalamin In cblD-MMA/HC fibroblasts, an MMADHC construct with improved mitochondrial targeting increased adenosylcobalamin 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 increased 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

  3. 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

In the sources

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

    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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