Component

Human intrinsic factor-cobalamin complex

Human intrinsic factor carrying a cobalamin ligand; exact upper ligand retained in individual experiment exposure.

4 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 acts on it

  1. The human cubilin P1297L CUB5-8 fragment showed severalfold higher dissociation constant for IF-cobalamin than wild type, mainly from a lower association rate.

    Human cubilin P1297L variant → Human intrinsic factor-cobalamin complex source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Human wild-type/P1297L fragments expressed in CHO cells; SPR
    exposure
    Site-directed P1297L substitution
    limitations
    Fragment binding assay; not every CUBN variant shares this mechanism.
    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 cubilin variant binds its B12 carrier less efficiently.
    primary_references
    [kristiansen-2000-p1297l] Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. (2000). https://pubmed.ncbi.nlm.nih.gov/10887099/ DOI: 10.1182/blood.v96.2.405
    tissue_or_cell_type
    Ileal receptor ligand-binding model
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 270–281

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human wild-type/P1297L fragments expressed in CHO cells; SPR · source_derived_draft · unverified_draft

    ### b12-abs-cubn-p1297l-affinity The human cubilin P1297L CUB5-8 fragment showed severalfold higher dissociation constant for IF-cobalamin than wild type, mainly from a lower association rate. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This cubilin variant binds its B12 carrier less efficiently. organism: Homo sapiens tissue_or_cell_type: Ileal receptor ligand-binding model experimental_model: Human wild-type/P1297L fragments expressed in CHO cells; SPR limitations: Fragment binding assay; not every CUBN variant shares this mechanism. exposure: Site-directed P1297L substitution cross_nutrient: false [kristiansen-2000-p1297l] Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. (2000). https://pubmed.ncbi.nlm.nih.gov/10887099/ DOI: 10.1182/blood.v96.2.405
    Complete structured claim and evidence

  2. The 3.3-angstrom human IF-cobalamin/CUB5-8 structure showed two separated cubilin CUB domains engaging the two intrinsic factor domains.

    Human cubilin / CUBN → Human intrinsic factor-cobalamin complex source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Recombinant human proteins; X-ray crystallography, PDB 3KQ4
    exposure
    Purified IF-cobalamin plus CUB5-8 fragment
    limitations
    Partial receptor crystal structure; recognition does not by itself establish endocytosis kinetics.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Cubilin recognizes B12 carried by intrinsic factor.
    primary_references
    [andersen-2010-if-cubn] Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. (2010). https://pubmed.ncbi.nlm.nih.gov/20237569/ DOI: 10.1038/nature08874
    tissue_or_cell_type
    Extracellular ileal receptor recognition model

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 244–255

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human proteins; X-ray crystallography, PDB 3KQ4 · source_derived_draft · unverified_draft

    ### b12-abs-cubn-recognition The 3.3-angstrom human IF-cobalamin/CUB5-8 structure showed two separated cubilin CUB domains engaging the two intrinsic factor domains. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cubilin recognizes B12 carried by intrinsic factor. organism: Homo sapiens tissue_or_cell_type: Extracellular ileal receptor recognition model experimental_model: Recombinant human proteins; X-ray crystallography, PDB 3KQ4 limitations: Partial receptor crystal structure; recognition does not by itself establish endocytosis kinetics. exposure: Purified IF-cobalamin plus CUB5-8 fragment cross_nutrient: true [andersen-2010-if-cubn] Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. (2010). https://pubmed.ncbi.nlm.nih.gov/20237569/ DOI: 10.1038/nature08874
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Type II antibodies prevented absorption in pernicious-anemia patients when added to a preformed intrinsic-factor-B12 complex.

    Human type II intrinsic-factor binding autoantibodies → Intestinal cobalamin absorption source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Human absorption experiments with preassembled IF-B12
    exposure
    IF plus B12 followed by type II antibody
    limitations
    Demonstrates impaired absorption; does not identify an epitope or directly prove contact competition at cubilin.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Other antibodies interfered even after B12 had bound its carrier.
    primary_references
    [schade-1967-if-antibody] Studies on antibody to intrinsic factor. (1967). https://pubmed.ncbi.nlm.nih.gov/6021209/ DOI: 10.1172/jci105563
    tissue_or_cell_type
    Intestinal intrinsic-factor-dependent absorption
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 517–528

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human absorption experiments with preassembled IF-B12 · source_derived_draft · unverified_draft

    ### b12-abs-if-antibody-preformed-complex Type II antibodies prevented absorption in pernicious-anemia patients when added to a preformed intrinsic-factor-B12 complex. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Other antibodies interfered even after B12 had bound its carrier. organism: Homo sapiens tissue_or_cell_type: Intestinal intrinsic-factor-dependent absorption experimental_model: Human absorption experiments with preassembled IF-B12 limitations: Demonstrates impaired absorption; does not identify an epitope or directly prove contact competition at cubilin. exposure: IF plus B12 followed by type II antibody cross_nutrient: false [schade-1967-if-antibody] Studies on antibody to intrinsic factor. (1967). https://pubmed.ncbi.nlm.nih.gov/6021209/ DOI: 10.1172/jci105563
    Complete structured claim and evidence

  2. The authors attributed diminished B12 absorption and low serum B12 and transcobalamin-bound B12 during metformin to a calcium-dependent ileal membrane antagonism, since uptake of the B12-intrinsic factor complex by ileal cell surface receptors is calcium-dependent.

    Metformin → Intestinal cobalamin absorption source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/metformin-research/10977010.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7aed1bfb7ee680b248e083db467fd4a8199ac933e8a12b4c6ba08f9931a7794b", "start_char": 0, "end_char": 1267, "text_sha256": "7aed1bfb7ee680b248e083db467fd4a8199ac933e8a12b4c6ba08f9931a7794b"}
    experimental_model
    Comparative study in 21 people with type 2 diabetes, 14 switched to metformin, with oral calcium supplementation
    exposure
    Metformin for three months, then oral calcium supplementation
    limitations
    A small, non-randomised comparative study. The calcium-dependent ileal mechanism is the authors’ interpretation of the reversal, not a direct measurement of receptor binding.
    nutrient_topic
    Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
    organism
    Human
    plain_language
    The proposed step is the calcium-dependent grab of the vitamin at the ileal cell surface.
    primary_references
    [metformin-p10977010] Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. (2000). https://pubmed.ncbi.nlm.nih.gov/10977010/ DOI: 10.2337/diacare.23.9.1227
    tissue_or_cell_type
    Ileal absorption
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1152–1163

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparative study in 21 people with type 2 diabetes, 14 switched to metformin, with oral calcium supplementation · source_derived_draft · unverified_draft

    ### metformin-b12-calcium-mechanism The authors attributed diminished B12 absorption and low serum B12 and transcobalamin-bound B12 during metformin to a calcium-dependent ileal membrane antagonism, since uptake of the B12-intrinsic factor complex by ileal cell surface receptors is calcium-dependent. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The proposed step is the calcium-dependent grab of the vitamin at the ileal cell surface. organism: Human tissue_or_cell_type: Ileal absorption experimental_model: Comparative study in 21 people with type 2 diabetes, 14 switched to metformin, with oral calcium supplementation limitations: A small, non-randomised comparative study. The calcium-dependent ileal mechanism is the authors’ interpretation of the reversal, not a direct measurement of receptor binding. exposure: Metformin for three months, then oral calcium supplementation evidence_span: {"source_cache": "artifacts/metformin-research/10977010.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7aed1bfb7ee680b248e083db467fd4a8199ac933e8a12b4c6ba08f9931a7794b", "start_char": 0, "end_char": 1267, "text_sha256": "7aed1bfb7ee680b248e083db467fd4a8199ac933e8a12b4c6ba08f9931a7794b"} [metformin-p10977010] Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. (2000). https://pubmed.ncbi.nlm.nih.gov/10977010/ DOI: 10.2337/diacare.23.9.1227
    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.

    Evidence, AI assistance and curation standards