Component

Human serum transferrin / TF

Human serum transferrin / TF. Species, exposure and limitations are retained in each linked claim.

7 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. Cr(III)-transferrin crystals contained a chromium-loaded closed C-terminal lobe and an open empty N-terminal lobe; two tyrosines, histidine, aspartate and chelating malonate coordinated the metal.

    Human serum transferrin / TF → Trivalent chromium / Cr(III) source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/chromium-research/32650146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "826e2d7f86ec2016d526ca8a8858db0249f4797aad842189d7f0359b6f375f85", "start_char": 0, "end_char": 1004, "text_sha256": "826e2d7f86ec2016d526ca8a8858db0249f4797aad842189d7f0359b6f375f85"}
    experimental_model
    X-ray crystallography of chromium-loaded transferrin
    exposure
    Cr(III)-transferrin crystallized with malonate as the synergistic anion
    limitations
    Crystal ligands and occupancy depend on preparation; malonate is not evidence that every circulating complex has the same coordination environment.
    nutrient_topic
    Chromium research collection; topical membership is not evidence of a direct dietary effect. · Chromium
    organism
    Human serum transferrin
    plain_language
    The iron-carrier protein can bind chromium in a structurally characterized pocket.
    primary_references
    [chromium-p32650146] X-ray structure of chromium(III)-containing transferrin: First structure of a physiological Cr(III)-binding protein. (2020). https://pubmed.ncbi.nlm.nih.gov/32650146/ DOI: 10.1016/j.jinorgbio.2020.111101
    tissue_or_cell_type
    Protein crystals

    Chromium: transport, insulin signaling, nutrient interactions and essentiality debate (2026-09-17) · lines 146–157

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of chromium-loaded transferrin · source_derived_draft · unverified_draft

    ### chromium-transferrin-crystal Cr(III)-transferrin crystals contained a chromium-loaded closed C-terminal lobe and an open empty N-terminal lobe; two tyrosines, histidine, aspartate and chelating malonate coordinated the metal. Condition category: normal nutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The iron-carrier protein can bind chromium in a structurally characterized pocket. organism: Human serum transferrin tissue_or_cell_type: Protein crystals experimental_model: X-ray crystallography of chromium-loaded transferrin limitations: Crystal ligands and occupancy depend on preparation; malonate is not evidence that every circulating complex has the same coordination environment. exposure: Cr(III)-transferrin crystallized with malonate as the synergistic anion evidence_span: {"source_cache": "artifacts/chromium-research/32650146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "826e2d7f86ec2016d526ca8a8858db0249f4797aad842189d7f0359b6f375f85", "start_char": 0, "end_char": 1004, "text_sha256": "826e2d7f86ec2016d526ca8a8858db0249f4797aad842189d7f0359b6f375f85"} [chromium-p32650146] X-ray structure of chromium(III)-containing transferrin: First structure of a physiological Cr(III)-binding protein. (2020). https://pubmed.ncbi.nlm.nih.gov/32650146/ DOI: 10.1016/j.jinorgbio.2020.111101
    Complete structured claim and evidence

  2. The transferrin-cycle model supported by the binding experiments releases iron in acidified endosomes while apotransferrin remains receptor-bound.

    Human serum transferrin / TF → Transferrin-dependent endosomal iron delivery to cytosol source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"}
    experimental_model
    Receptor binding at controlled pH and transferrin cycle analysis
    exposure
    Apotransferrin and diferric transferrin binding at acidic versus neutral pH
    limitations
    The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover.
    nutrient_topic
    Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
    organism
    Cultured-cell transferrin receptor system
    plain_language
    The carrier gives up its iron inside an acidic compartment but stays attached to its return transport.
    primary_references
    [iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
    tissue_or_cell_type
    Cell surface and endosomal recycling model

    Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 420–431

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor binding at controlled pH and transferrin cycle analysis · source_derived_draft · unverified_draft

    ### iron-tf-acidic-release The transferrin-cycle model supported by the binding experiments releases iron in acidified endosomes while apotransferrin remains receptor-bound. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier gives up its iron inside an acidic compartment but stays attached to its return transport. organism: Cultured-cell transferrin receptor system tissue_or_cell_type: Cell surface and endosomal recycling model experimental_model: Receptor binding at controlled pH and transferrin cycle analysis limitations: The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover. exposure: Apotransferrin and diferric transferrin binding at acidic versus neutral pH evidence_span: {"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"} [iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
    Complete structured claim and evidence

What acts on it

  1. V(V) and V(IV) bound vacant transferrin iron-binding sites in culture medium even with a 20-fold molar excess of albumin, without displacing already-bound Fe(III) under those conditions.

    Vanadate(V), protonation/speciation dependent → Human serum transferrin / TF source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human transferrin binding experiments under normoxic conditions.
    limitations
    Does not establish systemic iron deficiency or competition magnitude at dietary exposures.
    nutrient_topic
    Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium
    plain_language
    Vanadium can occupy available metal-binding sites without stripping out all bound iron.
    primary_references
    Vanadium(V/IV)-Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32578416/ · DOI 10.1021/acs.inorgchem.0c00926

    Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 190–196

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transferrin binding experiments under normoxic conditions. · source_derived_draft · unverified_draft

    ## vanadium-tf-binding Vanadium can occupy available metal-binding sites without stripping out all bound iron. V(V) and V(IV) bound vacant transferrin iron-binding sites in culture medium even with a 20-fold molar excess of albumin, without displacing already-bound Fe(III) under those conditions. Model: Human transferrin binding experiments under normoxic conditions. Limitations: Does not establish systemic iron deficiency or competition magnitude at dietary exposures. Evidence access: Primary abstract Vanadium(V/IV)-Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32578416/ · DOI 10.1021/acs.inorgchem.0c00926
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Crystals of C-lobe-ferric human transferrin exposed to vanadyl acetylacetonate contained a two-vanadium(V) unit linked to Tyr188 rather than intact V(IV) acetylacetonate.

    Bis(acetylacetonato)oxovanadium(IV) → Human C-lobe-ferric transferrin Tyr188-linked divanadate(V) adduct source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human protein crystallography; 5 mM compound and crystallization conditions.
    limitations
    Reaction/crystal structure does not demonstrate the same species dominates human blood.
    nutrient_topic
    Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium
    plain_language
    The species bound to a protein can differ from the compound originally added.
    primary_references
    First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41545537/ · DOI 10.1038/s42004-026-01891-1

    Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 214–220

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human protein crystallography; 5 mM compound and crystallization conditions. · source_derived_draft · unverified_draft

    ## vanadium-tf-crystal-transformation The species bound to a protein can differ from the compound originally added. Crystals of C-lobe-ferric human transferrin exposed to vanadyl acetylacetonate contained a two-vanadium(V) unit linked to Tyr188 rather than intact V(IV) acetylacetonate. Model: Human protein crystallography; 5 mM compound and crystallization conditions. Limitations: Reaction/crystal structure does not demonstrate the same species dominates human blood. Evidence access: Primary full text First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41545537/ · DOI 10.1038/s42004-026-01891-1
    Complete structured claim and evidence

  2. Vanadium binding did not increase transferrin affinity for TfR1 at pH 7.4, but disrupted conformational changes at pH 5.6 with citrate in the transferrin-cycle model.

    Human transferrin bound to vanadium(V/IV) → Endosome-like conformational change of vanadium-bound human transferrin source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Biolayer interferometry and electrophoretic model of the human transferrin cycle.
    limitations
    Return of undissociated V–transferrin to the surface is the authors’ proposed explanation, not directly imaged trafficking.
    nutrient_topic
    Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium
    plain_language
    Receptor recognition and release during endosomal processing are different steps.
    primary_references
    Vanadium(V/IV)-Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32578416/ · DOI 10.1021/acs.inorgchem.0c00926

    Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 206–212

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biolayer interferometry and electrophoretic model of the human transferrin cycle. · source_derived_draft · unverified_draft

    ## vanadium-tf-cycle Receptor recognition and release during endosomal processing are different steps. Vanadium binding did not increase transferrin affinity for TfR1 at pH 7.4, but disrupted conformational changes at pH 5.6 with citrate in the transferrin-cycle model. Model: Biolayer interferometry and electrophoretic model of the human transferrin cycle. Limitations: Return of undissociated V–transferrin to the surface is the authors’ proposed explanation, not directly imaged trafficking. Evidence access: Primary abstract Vanadium(V/IV)-Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32578416/ · DOI 10.1021/acs.inorgchem.0c00926
    Complete structured claim and evidence

  3. The vanadium adduct retained an open N-lobe and closed iron-containing C-lobe with little overall structural change.

    Human C-lobe-ferric transferrin Tyr188-linked divanadate(V) adduct → Open N-lobe conformation of monoferric human transferrin source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human transferrin crystal comparison.
    limitations
    Compatibility with receptor recognition is a structural interpretation, not a completed cellular uptake cycle; not a contradiction of the A549 transport study.
    nutrient_topic
    Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium
    plain_language
    A binding structure alone does not demonstrate successful cellular delivery.
    primary_references
    First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41545537/ · DOI 10.1038/s42004-026-01891-1

    Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 222–228

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transferrin crystal comparison. · source_derived_draft · unverified_draft

    ## vanadium-tf-open-lobe A binding structure alone does not demonstrate successful cellular delivery. The vanadium adduct retained an open N-lobe and closed iron-containing C-lobe with little overall structural change. Model: Human transferrin crystal comparison. Limitations: Compatibility with receptor recognition is a structural interpretation, not a completed cellular uptake cycle; not a contradiction of the A549 transport study. Evidence access: Primary full text First crystal structure of an adduct formed upon reaction of a vanadium compound with human serum transferrin. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41545537/ · DOI 10.1038/s42004-026-01891-1
    Complete structured claim and evidence

  4. Apotransferrin bound receptors at pH 5.4 but dissociated rapidly when pH was raised to 7.0.

    Human transferrin receptor 1 / TFRC → Transferrin and transferrin-receptor recycling source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"}
    experimental_model
    Receptor binding at controlled pH and transferrin cycle analysis
    exposure
    Apotransferrin and diferric transferrin binding at acidic versus neutral pH
    limitations
    The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover.
    nutrient_topic
    Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
    organism
    Cultured-cell transferrin receptor system
    plain_language
    Returning to the neutral cell surface allows the empty carrier to detach.
    primary_references
    [iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
    tissue_or_cell_type
    Cell surface and endosomal recycling model

    Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 433–444

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor binding at controlled pH and transferrin cycle analysis · source_derived_draft · unverified_draft

    ### iron-tf-recycling Apotransferrin bound receptors at pH 5.4 but dissociated rapidly when pH was raised to 7.0. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Returning to the neutral cell surface allows the empty carrier to detach. organism: Cultured-cell transferrin receptor system tissue_or_cell_type: Cell surface and endosomal recycling model experimental_model: Receptor binding at controlled pH and transferrin cycle analysis limitations: The indexed abstract does not identify the cell line; its experiments support a pH-dependent trafficking model, not direct measures of whole-body iron turnover. exposure: Apotransferrin and diferric transferrin binding at acidic versus neutral pH evidence_span: {"source_cache": "artifacts/iron-research/6300903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852", "start_char": 0, "end_char": 906, "text_sha256": "29d23cdaaacd30003c1f3e70935d7ab5ccbb1612379d6e650d356d1235438852"} [iron-p6300903] pH and the recycling of transferrin during receptor-mediated endocytosis. (1983). https://pubmed.ncbi.nlm.nih.gov/6300903/ DOI: 10.1073/pnas.80.8.2258
    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