Component
Human MMACHC–MMADHC cobalamin coordination complex
Complex with cobalamin in the MMACHC pocket and a cysteine-derived sulfur ligand donated by MMADHC.
3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
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.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
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.
Where it participates (unsigned role)
Human MMADHC donated the Cys261 sulfur ligand to MMACHC-bound cob(II)alamin, forming an interprotein complex that oxidized to thiolato-cob(III)alamin.
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 evidenceReduced, 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.
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 evidenceHuman MMADHC delta123 carrying T182N showed strongly reduced complex formation with full-length human MMACHC after MeCbl/GSH incubation, compared with matched delta123 MMADHC.
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
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.