Nutrient chapter

Zinc

Independent biological entity. Read linked claims for experimental scope and context.

126 recorded mechanisms · 29 availability situations · 5 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

CNNM2 coexpression increased TRPM7-dependent zinc influx, and the TRPM7 E1047K pore mutant prevented this increase.
CNNM2 → Cellular zinc influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
A protein associated with Mg homeostasis regulates a Zn-permeable channel in culture; nutritional co-dependence was not tested.
evidence-system
Coexpression, TRPM7 knockout and pore-inactivation tests
experimental_model
Coexpression, TRPM7 knockout and pore-inactivation tests
limitations
Zinc is a divalent-flux reporter here; this does not establish CNNM2 as a magnesium pore or dietary Mg-to-Zn dependence.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human proteins and human-derived cells
plain_language
CNNM2 can regulate entry through a separate channel whose pore carries the ion.
primary_references
[bai-2021-cnnm-trpm7] CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8726484/ DOI: 10.1371/journal.pbio.3001496
tissue
HEK293-family cells; supporting HAP1 cells
tissue_or_cell_type
HEK293-family cells; supporting HAP1 cells
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1151–1163
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coexpression, TRPM7 knockout and pore-inactivation tests · source_derived_draft · unverified_draft
### cnnm2-stimulates-trpm7-zinc-influx CNNM2 coexpression increased TRPM7-dependent zinc influx, and the TRPM7 E1047K pore mutant prevented this increase. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: CNNM2 can regulate entry through a separate channel whose pore carries the ion. organism: Human proteins and human-derived cells tissue_or_cell_type: HEK293-family cells; supporting HAP1 cells experimental_model: Coexpression, TRPM7 knockout and pore-inactivation tests limitations: Zinc is a divalent-flux reporter here; this does not establish CNNM2 as a magnesium pore or dietary Mg-to-Zn dependence. cross_nutrient: A protein associated with Mg homeostasis regulates a Zn-permeable channel in culture; nutritional co-dependence was not tested. evidence-system: Coexpression, TRPM7 knockout and pore-inactivation tests tissue: HEK293-family cells; supporting HAP1 cells [bai-2021-cnnm-trpm7] CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8726484/ DOI: 10.1371/journal.pbio.3001496
Complete structured claim and evidence
Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content.
Zinc(II) ion → Betaine-homocysteine S-methyltransferase / BHMT source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc supports parallel remethylation.
experimental_model
Recombinant human BHMT and human liver-derived BHMT.
limitations
Demetallation is not dietary zinc deficiency.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
The betaine route requires a zinc-containing enzyme.
primary_references
[millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–632
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BHMT and human liver-derived BHMT. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-zinc Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The betaine route requires a zinc-containing enzyme. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Demetallation is not dietary zinc deficiency. cross_nutrient: Zinc supports parallel remethylation. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
Complete structured claim and evidence
Human GCPII crystal structures resolved two zinc ions at the catalytic center, bridged by water or hydroxide and Asp387.
Zinc(II) ion → Human glutamate carboxypeptidase II / FOLH1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc-folate: molecular catalytic-site dependency; dietary zinc deficiency was not tested.
experimental_model
Recombinant human GCPII crystallography
exposure
Glutamate, phosphate and inhibitor-bound structures
limitations
Structural cofactor evidence does not establish zinc intake thresholds.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
The folate-processing enzyme contains a two-zinc catalytic site.
primary_references
[mesters2006] Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer (2006). https://pubmed.ncbi.nlm.nih.gov/16467855/ DOI: 10.1038/sj.emboj.7600969
tissue_or_cell_type
Purified recombinant protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 118–129
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GCPII crystallography · source_derived_draft · unverified_draft
### folate-gcpii-zinc-catalytic-center Human GCPII crystal structures resolved two zinc ions at the catalytic center, bridged by water or hydroxide and Asp387. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The folate-processing enzyme contains a two-zinc catalytic site. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein experimental_model: Recombinant human GCPII crystallography limitations: Structural cofactor evidence does not establish zinc intake thresholds. exposure: Glutamate, phosphate and inhibitor-bound structures cross_nutrient: Zinc-folate: molecular catalytic-site dependency; dietary zinc deficiency was not tested. [mesters2006] Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer (2006). https://pubmed.ncbi.nlm.nih.gov/16467855/ DOI: 10.1038/sj.emboj.7600969
Complete structured claim and evidence
Calcium at TNAP site M3 supported about 40% of the activity of Mg/Zn-TNAP at pH 7.4 and 9.8.
Calcium ion → Mg2+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium/Mg substitution at one enzyme site, not whole-body interchangeability.
experimental_model
Recombinant enzyme comparison. Activity was measured using artificial pNPP substrate.
limitations
Site-specific substitution is not evidence that dietary calcium replaces magnesium requirements. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Calcium can occupy this magnesium site, but gives a different enzyme response.
primary_references
[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1479–1489
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme comparison. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft
### mg-alpl-calcium-partial-substitution Calcium at TNAP site M3 supported about 40% of the activity of Mg/Zn-TNAP at pH 7.4 and 9.8. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium can occupy this magnesium site, but gives a different enzyme response. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Recombinant enzyme comparison. Activity was measured using artificial pNPP substrate. limitations: Site-specific substitution is not evidence that dietary calcium replaces magnesium requirements. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Calcium/Mg substitution at one enzyme site, not whole-body interchangeability. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity.
Mg2+ → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization.
experimental_model
Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate.
limitations
Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
This mineralization enzyme needs the right metals in different sites.
primary_references
[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1467–1477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft
### mg-zinc-alpl-reconstitution Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mineralization enzyme needs the right metals in different sites. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. limitations: Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
Very high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH.
Calcium ion → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium/Zn/Mg interaction depends on site occupancy and local conditions.
experimental_model
Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate.
limitations
Local experimental concentrations cannot be converted to dietary dose cutoffs. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The same calcium ion can activate one site and interfere with another.
primary_references
[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1491–1501
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft
### mg-alpl-high-calcium-zinc-displacement Very high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same calcium ion can activate one site and interfere with another. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate. limitations: Local experimental concentrations cannot be converted to dietary dose cutoffs. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Calcium/Zn/Mg interaction depends on site occupancy and local conditions. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
The same zinc-deficient rats showed increased retinal oxidase activity, with no detected REH/ARAT activity changes.
Zinc → Hepatic retinal oxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Same hepatic activity assays.
limitations
Activity is not whole-body flux or proof of a direct zinc-binding requirement.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Rattus norvegicus
plain_language
Vitamin A processing did not simply stop at every step.
primary_references
[va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995
tissue_or_cell_type
Liver
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1531–1540
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same hepatic activity assays. · source_derived_draft · unverified_draft
### va-zinc-deficiency-retinal-oxidation-increase The same zinc-deficient rats showed increased retinal oxidase activity, with no detected REH/ARAT activity changes. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A processing did not simply stop at every step. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Same hepatic activity assays. limitations: Activity is not whole-body flux or proof of a direct zinc-binding requirement. [va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995
Complete structured claim and evidence
In women with low initial zinc, vitamin A plus zinc improved night-vision recovery versus double placebo; zinc alone did not.
Zinc → Night vision source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Zinc/vitamin A -> dark-adaptation response.
experimental_model
Three-week zinc randomization, existing vitamin A allocation.
limitations
Not a universal zinc requirement; relative estimate had a wide confidence interval.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
An additional shortage may limit the response, but this result was subgroup-specific.
primary_references
[va-christian2001] Zinc supplementation might potentiate the effect of vitamin A in restoring night vision in pregnant Nepalese women (2001). https://pubmed.ncbi.nlm.nih.gov/11382658/ DOI: 10.1093/ajcn/73.6.1045
tissue_or_cell_type
Human visual function
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1507–1517
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-week zinc randomization, existing vitamin A allocation. · source_derived_draft · unverified_draft
### va-zinc-night-vision-subgroup In women with low initial zinc, vitamin A plus zinc improved night-vision recovery versus double placebo; zinc alone did not. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: An additional shortage may limit the response, but this result was subgroup-specific. organism: Homo sapiens tissue_or_cell_type: Human visual function experimental_model: Three-week zinc randomization, existing vitamin A allocation. limitations: Not a universal zinc requirement; relative estimate had a wide confidence interval. cross_nutrient: Zinc/vitamin A -> dark-adaptation response. [va-christian2001] Zinc supplementation might potentiate the effect of vitamin A in restoring night vision in pregnant Nepalese women (2001). https://pubmed.ncbi.nlm.nih.gov/11382658/ DOI: 10.1093/ajcn/73.6.1045
Complete structured claim and evidence
Zinc increased plasma retinol and transthyretin versus placebo; the RBP increase was not significant.
Zinc → Plasma retinol concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc -> vitamin A biomarkers.
experimental_model
Six-month preschool trial.
limitations
No direct proof of restored liver release or increased RBP synthesis.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
Zinc status can influence vitamin A transport-related blood measurements.
primary_references
[va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789
tissue_or_cell_type
Plasma
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1483–1493
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month preschool trial. · source_derived_draft · unverified_draft
### va-zinc-improves-retinol-marker Zinc increased plasma retinol and transthyretin versus placebo; the RBP increase was not significant. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc status can influence vitamin A transport-related blood measurements. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Six-month preschool trial. limitations: No direct proof of restored liver release or increased RBP synthesis. cross_nutrient: Zinc -> vitamin A biomarkers. [va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789
Complete structured claim and evidence
The pooled high-zinc groups also had lower Mg balance.
Zinc sulfate → Whole-body magnesium balance source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc/Mg intake balance; exposure-dependent.
experimental_model
Same adult metabolic-balance experiment.
limitations
Not a molecular transporter competition assay or evidence that every zinc dose depletes Mg.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Absorption interference was accompanied by a change in net magnesium balance.
primary_references
[mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
tissue_or_cell_type
Human intestinal absorption and metabolic balance
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1590–1600
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same adult metabolic-balance experiment. · source_derived_draft · unverified_draft
### mg-high-zinc-lowers-balance The pooled high-zinc groups also had lower Mg balance. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorption interference was accompanied by a change in net magnesium balance. organism: Homo sapiens tissue_or_cell_type: Human intestinal absorption and metabolic balance experimental_model: Same adult metabolic-balance experiment. limitations: Not a molecular transporter competition assay or evidence that every zinc dose depletes Mg. cross_nutrient: Zinc/Mg intake balance; exposure-dependent. [mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
Complete structured claim and evidence
ZnCl2 did not restore isomerohydrolase activity after metal chelation in the bovine RPE assay, whereas FeSO4 did.
Zinc(II) ion → RPE65 retinoid isomerohydrolase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron and zinc are not interchangeable RPE65 cofactors in the tested preparation.
experimental_model
Metal-rescue comparison
limitations
Does not test systemic zinc status or other zinc-dependent visual functions.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Bos taurus
plain_language
Zinc could not replace iron in this enzyme assay.
primary_references
[moiseyev-2006] RPE65 is an iron(II)-dependent isomerohydrolase in the retinoid visual cycle (2006). https://pubmed.ncbi.nlm.nih.gov/16319067/ DOI: 10.1074/jbc.M508903200
tissue_or_cell_type
RPE microsomes
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 689–699
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metal-rescue comparison · source_derived_draft · unverified_draft
### a-vision-rpe65-zinc-not-substitute ZnCl2 did not restore isomerohydrolase activity after metal chelation in the bovine RPE assay, whereas FeSO4 did. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc could not replace iron in this enzyme assay. organism: Bos taurus tissue_or_cell_type: RPE microsomes experimental_model: Metal-rescue comparison limitations: Does not test systemic zinc status or other zinc-dependent visual functions. cross_nutrient: Iron and zinc are not interchangeable RPE65 cofactors in the tested preparation. [moiseyev-2006] RPE65 is an iron(II)-dependent isomerohydrolase in the retinoid visual cycle (2006). https://pubmed.ncbi.nlm.nih.gov/16319067/ DOI: 10.1074/jbc.M508903200
Complete structured claim and evidence
Zinc-deficient rats had lower hepatic retinol-oxidizing ADH activity and greater hepatic vitamin A content.
Zinc → Hepatic retinol-oxidizing ADH activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Zinc -> hepatic retinoid metabolism.
experimental_model
Pair-feeding controls; three weeks.
limitations
Does not show that every retinol dehydrogenase is a zinc enzyme.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Rattus norvegicus
plain_language
Zinc depletion changed retinoid handling in the liver.
primary_references
[va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995
tissue_or_cell_type
Liver
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1519–1529
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pair-feeding controls; three weeks. · source_derived_draft · unverified_draft
### va-zinc-deficiency-adh-decrease Zinc-deficient rats had lower hepatic retinol-oxidizing ADH activity and greater hepatic vitamin A content. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc depletion changed retinoid handling in the liver. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Pair-feeding controls; three weeks. limitations: Does not show that every retinol dehydrogenase is a zinc enzyme. cross_nutrient: Zinc -> hepatic retinoid metabolism. [va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995
Complete structured claim and evidence
Iron increased plasma retinol, RBP and transthyretin; the combined iron/zinc arm increased retinol without significant carrier-protein increases.
Iron → Plasma retinol concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron/zinc -> retinoid transport markers.
experimental_model
Same factorial trial.
limitations
Measured biomarkers do not prove the molecular mechanism.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Homo sapiens
plain_language
The two minerals did not produce identical carrier-protein responses.
primary_references
[va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789
tissue_or_cell_type
Plasma
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1495–1505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same factorial trial. · source_derived_draft · unverified_draft
### va-iron-improves-retinol-marker Iron increased plasma retinol, RBP and transthyretin; the combined iron/zinc arm increased retinol without significant carrier-protein increases. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two minerals did not produce identical carrier-protein responses. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Same factorial trial. limitations: Measured biomarkers do not prove the molecular mechanism. cross_nutrient: Iron/zinc -> retinoid transport markers. [va-munoz2000] Iron and zinc supplementation improves indicators of vitamin A status of Mexican preschoolers (2000). https://pubmed.ncbi.nlm.nih.gov/10702174/ DOI: 10.1093/ajcn/71.3.789
Complete structured claim and evidence
High-dose supplemental zinc reduced measured Mg absorption in the pooled metabolic-balance groups.
Zinc sulfate → Intestinal magnesium absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc -> magnesium availability; calcium intake recorded as context.
experimental_model
Adult men; three dietary calcium strata.
exposure
142 mg Zn/day as sulfate; calcium 230, 500 or 800 mg/day. Only the 500-mg stratum individually significant; pooled groups significant.
limitations
142 mg zinc/day is a high experimental exposure; ordinary food zinc effects and a shared transporter were not established.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Large zinc exposure can interfere with magnesium uptake.
primary_references
[mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
tissue_or_cell_type
Human intestinal absorption and metabolic balance
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1577–1588
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult men; three dietary calcium strata. · source_derived_draft · unverified_draft
### mg-high-zinc-lowers-absorption High-dose supplemental zinc reduced measured Mg absorption in the pooled metabolic-balance groups. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Large zinc exposure can interfere with magnesium uptake. organism: Homo sapiens tissue_or_cell_type: Human intestinal absorption and metabolic balance experimental_model: Adult men; three dietary calcium strata. limitations: 142 mg zinc/day is a high experimental exposure; ordinary food zinc effects and a shared transporter were not established. cross_nutrient: Zinc -> magnesium availability; calcium intake recorded as context. exposure: 142 mg Zn/day as sulfate; calcium 230, 500 or 800 mg/day. Only the 500-mg stratum individually significant; pooled groups significant. [mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
Complete structured claim and evidence
Across approximately 150,000 people, carriers of 12 rare SLC30A8 truncating variants had 65% lower type 2 diabetes risk.
Human SLC30A8 protein-truncating variant carrier state → Incidence of type 2 diabetes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
curation_topic
zinc · Zinc
experimental_condition
Noncarrier Truncating-variant carrier · Human SLC30A8 protein-truncating variant carrier state Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "Truncating-variant carrier", "comparator": "Noncarrier", "endpoint": "T2D risk", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "human-slc30a8-truncating-genotype", "state": "Truncating-variant carrier"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human genetic association across five ancestry groups
limitations
Publisher abstract reviewed; genetic transporter loss is not dietary zinc restriction or a demonstrated supplement effect.
primary_references
Flannick et al. 2014; DOI:10.1038/ng.2915; PMCID:PMC4051628; https://www.nature.com/articles/ng.2915
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 6–6
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human genetic association across five ancestry groups · source_derived_draft · unverified_draft
Across approximately 150,000 people, carriers of 12 rare SLC30A8 truncating variants had 65% lower type 2 diabetes risk. Model: Human genetic association across five ancestry groups. Limits: Publisher abstract reviewed; genetic transporter loss is not dietary zinc restriction or a demonstrated supplement effect. Primary reference: Flannick et al. 2014; DOI:10.1038/ng.2915; PMCID:PMC4051628; https://www.nature.com/articles/ng.2915
Complete structured claim and evidence
SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation.
Human stem-cell-derived SLC30A8-null beta cells → Human beta-cell cytosolic free zinc pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
curation_topic
zinc · Zinc
experimental_condition
Wild-type cells SLC30A8 knockout · Human stem-cell-derived SLC30A8-null beta cells Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SLC30A8 knockout", "comparator": "Wild-type cells", "endpoint": "Cytosolic free zinc", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "human-slc30a8-null-beta-cells", "state": "SLC30A8 knockout"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed
limitations
Compartment-specific sensor measurement; not total-body zinc.
primary_references
SLC30A8 stem-cell study; 2023; PMCID:PMC10047077; https://pmc.ncbi.nlm.nih.gov/articles/PMC10047077/
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 9–9
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed · source_derived_draft · unverified_draft
SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation. Model: Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed. Limits: Compartment-specific sensor measurement; not total-body zinc. Primary reference: SLC30A8 stem-cell study; 2023; PMCID:PMC10047077; https://pmc.ncbi.nlm.nih.gov/articles/PMC10047077/
Complete structured claim and evidence
SLC30A8-null and R138X beta cells had fewer crystalline insulin granules; glucose-stimulated secretion was not impaired in the tested system.
Human stem-cell-derived SLC30A8-null beta cells → Human beta-cell insulin-granule crystallization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
curation_topic
zinc · Zinc
experimental_condition
Wild-type cells SLC30A8-null or R138X cells · Human stem-cell-derived SLC30A8-null beta cells Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "SLC30A8-null or R138X cells", "comparator": "Wild-type cells", "endpoint": "Granule crystallization", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "human-slc30a8-null-beta-cells", "state": "SLC30A8-null or R138X cells"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed
limitations
Separate genotypes, not a combined knockout. Preserved secretion does not establish universal protection.
primary_references
SLC30A8 stem-cell study; 2023; PMCID:PMC10047077; https://pmc.ncbi.nlm.nih.gov/articles/PMC10047077/
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 12–12
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed · source_derived_draft · unverified_draft
SLC30A8-null and R138X beta cells had fewer crystalline insulin granules; glucose-stimulated secretion was not impaired in the tested system. Model: Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed. Limits: Separate genotypes, not a combined knockout. Preserved secretion does not establish universal protection. Primary reference: SLC30A8 stem-cell study; 2023; PMCID:PMC10047077; https://pmc.ncbi.nlm.nih.gov/articles/PMC10047077/
Complete structured claim and evidence
After 5 micromolar TPEN for 48 hours, apoptosis was lower in SLC30A8-null and R138X cells than treated wild-type cells.
Human stem-cell-derived SLC30A8-null beta cells → Human beta-cell apoptosis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
curation_topic
zinc · Zinc
experimental_condition
Wild-type cells with the same TPEN exposure Limited availability during TPEN exposure · Zinc Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_condition
Wild-type cells with the same TPEN exposure Null genotype; R138X tested separately · Human zinc transporter ZnT8 / SLC30A8 Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "ZnT8 loss plus TPEN", "comparator": "Wild-type cells with the same TPEN exposure", "endpoint": "TUNEL-positive beta cells", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "slc30a8", "state": "Null genotype; R138X tested separately"}, {"entity_slug": "zinc", "state": "Limited availability during TPEN exposure"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed
limitations
Chelator challenge, not dietary restriction; human in-vivo protection by this mechanism remains untested.
primary_references
SLC30A8 stem-cell study; 2023; PMCID:PMC10047077; https://pmc.ncbi.nlm.nih.gov/articles/PMC10047077/
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 15–15
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed · source_derived_draft · unverified_draft
After 5 micromolar TPEN for 48 hours, apoptosis was lower in SLC30A8-null and R138X cells than treated wild-type cells. Model: Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed. Limits: Chelator challenge, not dietary restriction; human in-vivo protection by this mechanism remains untested. Primary reference: SLC30A8 stem-cell study; 2023; PMCID:PMC10047077; https://pmc.ncbi.nlm.nih.gov/articles/PMC10047077/
Complete structured claim and evidence
Expression of mouse ZIP4 increased zinc influx into transfected cells.
Mouse ZIP4 (Slc39a4) → Cellular zinc influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Transfected mammalian cells
exposure
ZIP4 expression versus controls; abstract does not specify zinc concentration.
limitations
Transport in engineered cells establishes capacity, not the fraction of human dietary zinc absorption.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in cultured mammalian cells
plain_language
Mouse ZIP4 can bring zinc into cells.
primary_references
[zinc-trans-12801924] The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. (2003). https://pubmed.ncbi.nlm.nih.gov/12801924/ DOI: 10.1074/jbc.m305000200
tissue_or_cell_type
Cell plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 219–230
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected mammalian cells · source_derived_draft · unverified_draft
### zinc-trans-zip4-influx Expression of mouse ZIP4 increased zinc influx into transfected cells. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse ZIP4 can bring zinc into cells. organism: Mouse protein in cultured mammalian cells tissue_or_cell_type: Cell plasma membrane experimental_model: Transfected mammalian cells limitations: Transport in engineered cells establishes capacity, not the fraction of human dietary zinc absorption. exposure: ZIP4 expression versus controls; abstract does not specify zinc concentration. cross_nutrient: false [zinc-trans-12801924] The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. (2003). https://pubmed.ncbi.nlm.nih.gov/12801924/ DOI: 10.1074/jbc.m305000200
Complete structured claim and evidence
Dietary zinc deficiency increased mouse Zip4 mRNA by greater transcript stability rather than an increased relative transcription rate.
Zinc → Mouse Slc39a4 messenger RNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Mouse intestine with nuclear run-on assays; supporting Hepa-cell analyses
exposure
Defined zinc-deficient versus adequate diets; transcription assessed after 24 hours from gestational day 8.
limitations
Transcript stabilization in mice is not a serum-zinc threshold or proof that all zinc deficiency responses are post-transcriptional.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
With little dietary zinc, mice preserve the message used to make ZIP4.
primary_references
[zinc-trans-18020946] Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5). (2007). https://pubmed.ncbi.nlm.nih.gov/18020946/ DOI: 10.1515/bc.2007.149
tissue_or_cell_type
Small intestine; supporting cultured hepatic cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 232–243
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse intestine with nuclear run-on assays; supporting Hepa-cell analyses · source_derived_draft · unverified_draft
### zinc-trans-zip4-mrna-stability Dietary zinc deficiency increased mouse Zip4 mRNA by greater transcript stability rather than an increased relative transcription rate. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: With little dietary zinc, mice preserve the message used to make ZIP4. organism: Mus musculus tissue_or_cell_type: Small intestine; supporting cultured hepatic cells experimental_model: Mouse intestine with nuclear run-on assays; supporting Hepa-cell analyses limitations: Transcript stabilization in mice is not a serum-zinc threshold or proof that all zinc deficiency responses are post-transcriptional. exposure: Defined zinc-deficient versus adequate diets; transcription assessed after 24 hours from gestational day 8. cross_nutrient: false [zinc-trans-18020946] Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5). (2007). https://pubmed.ncbi.nlm.nih.gov/18020946/ DOI: 10.1515/bc.2007.149
Complete structured claim and evidence
Oral zinc repletion caused mouse ZIP4 internalization from enterocyte apical membranes after dietary zinc deficiency.
Zinc(II) ion → ZIP4 endocytosis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Dietary depletion followed by oral gavage and immunolocalization
exposure
Zinc-deficient weanlings for 10 days; 100 micromol ZnCl2/kg oral gavage with time-course localization.
limitations
Acute experimental repletion; the gavage is not a recommended human dose and internalization is distinct from later degradation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
After zinc becomes available again, intestinal cells pull ZIP4 away from their surface.
primary_references
[zinc-trans-18020946] Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5). (2007). https://pubmed.ncbi.nlm.nih.gov/18020946/ DOI: 10.1515/bc.2007.149
tissue_or_cell_type
Duodenal enterocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 245–256
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary depletion followed by oral gavage and immunolocalization · source_derived_draft · unverified_draft
### zinc-trans-zip4-repletion-endocytosis Oral zinc repletion caused mouse ZIP4 internalization from enterocyte apical membranes after dietary zinc deficiency. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: After zinc becomes available again, intestinal cells pull ZIP4 away from their surface. organism: Mus musculus tissue_or_cell_type: Duodenal enterocytes experimental_model: Dietary depletion followed by oral gavage and immunolocalization limitations: Acute experimental repletion; the gavage is not a recommended human dose and internalization is distinct from later degradation. exposure: Zinc-deficient weanlings for 10 days; 100 micromol ZnCl2/kg oral gavage with time-course localization. cross_nutrient: false [zinc-trans-18020946] Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5). (2007). https://pubmed.ncbi.nlm.nih.gov/18020946/ DOI: 10.1515/bc.2007.149
Complete structured claim and evidence
Elevated zinc stimulated human ZIP4 ubiquitination and degradation; a cytoplasmic histidine-rich region was required for this degradation response but dispensable for zinc-induced endocytosis.
Zinc(II) ion → ZIP4 protein degradation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Cultured cells expressing human ZIP4 with mutational analysis
exposure
Elevated zinc exposure; detailed concentration and cell lineage not specified in the abstract.
limitations
Abstract extraction; the region requirement does not mean every histidine acts as an independent sensor. This is zinc exposure, not demonstrated dietary deficiency.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Human protein in cultured cells
plain_language
Human ZIP4 has a zinc-triggered disposal response that is separate from removal from the surface.
primary_references
[zinc-trans-17202136] A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. (2007). https://pubmed.ncbi.nlm.nih.gov/17202136/ DOI: 10.1074/jbc.m610552200
tissue_or_cell_type
Cellular zinc-uptake machinery
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 258–269
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured cells expressing human ZIP4 with mutational analysis · source_derived_draft · unverified_draft
### zinc-trans-hzip4-degradation Elevated zinc stimulated human ZIP4 ubiquitination and degradation; a cytoplasmic histidine-rich region was required for this degradation response but dispensable for zinc-induced endocytosis. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human ZIP4 has a zinc-triggered disposal response that is separate from removal from the surface. organism: Human protein in cultured cells tissue_or_cell_type: Cellular zinc-uptake machinery experimental_model: Cultured cells expressing human ZIP4 with mutational analysis limitations: Abstract extraction; the region requirement does not mean every histidine acts as an independent sensor. This is zinc exposure, not demonstrated dietary deficiency. exposure: Elevated zinc exposure; detailed concentration and cell lineage not specified in the abstract. cross_nutrient: false [zinc-trans-17202136] A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. (2007). https://pubmed.ncbi.nlm.nih.gov/17202136/ DOI: 10.1074/jbc.m610552200
Complete structured claim and evidence
Enterocyte-specific Slc39a4 deletion rapidly lowered total zinc in mouse small intestine, liver and pancreas.
Mouse enterocyte-specific Slc39a4 knockout genotype → Tissue total zinc content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis
exposure
Conditional gene deletion compared with intact controls.
limitations
A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Disabling intestinal ZIP4 depleted zinc beyond the intestine.
primary_references
[zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766
tissue_or_cell_type
Small intestine, liver, pancreas
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 271–282
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis · source_derived_draft · unverified_draft
### zinc-trans-zip4-knockout-tissue-zinc Enterocyte-specific Slc39a4 deletion rapidly lowered total zinc in mouse small intestine, liver and pancreas. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disabling intestinal ZIP4 depleted zinc beyond the intestine. organism: Mus musculus tissue_or_cell_type: Small intestine, liver, pancreas experimental_model: Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis limitations: A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc. exposure: Conditional gene deletion compared with intact controls. cross_nutrient: false [zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766
Complete structured claim and evidence
In reconstituted human ZnT1 proteoliposomes, a transmembrane calcium gradient accelerated zinc transport and zinc addition drove calcium countertransport. Zinc transport persisted at a lower rate without the calcium gradient.
Calcium ion → Cellular zinc efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified full-length human ZnT1 in proteoliposomes; supporting HEK293T transport assays
exposure
Proteoliposomes with or without internal calcium, external zinc titration; zinc transport Km 0.38 ± 0.14 micromolar in this assay.
limitations
In vitro transport direction depends on liposome gradients. This does not establish dietary calcium dependence or a fixed physiological Zn/Ca ratio. Calcium versus proton coupling remains incompletely resolved.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens protein
plain_language
A calcium gradient helped purified human ZnT1 move zinc; some movement remained without it.
primary_references
[zinc-trans-38669333] Structural insights into the calcium-coupled zinc export of human ZnT1. (2024). https://pubmed.ncbi.nlm.nih.gov/38669333/ DOI: 10.1126/sciadv.adk5128
tissue_or_cell_type
Reconstituted membrane; cultured-cell plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 284–295
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length human ZnT1 in proteoliposomes; supporting HEK293T transport assays · source_derived_draft · unverified_draft
### zinc-trans-znt1-calcium-gradient In reconstituted human ZnT1 proteoliposomes, a transmembrane calcium gradient accelerated zinc transport and zinc addition drove calcium countertransport. Zinc transport persisted at a lower rate without the calcium gradient. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A calcium gradient helped purified human ZnT1 move zinc; some movement remained without it. organism: Homo sapiens protein tissue_or_cell_type: Reconstituted membrane; cultured-cell plasma membrane experimental_model: Purified full-length human ZnT1 in proteoliposomes; supporting HEK293T transport assays limitations: In vitro transport direction depends on liposome gradients. This does not establish dietary calcium dependence or a fixed physiological Zn/Ca ratio. Calcium versus proton coupling remains incompletely resolved. exposure: Proteoliposomes with or without internal calcium, external zinc titration; zinc transport Km 0.38 ± 0.14 micromolar in this assay. cross_nutrient: true [zinc-trans-38669333] Structural insights into the calcium-coupled zinc export of human ZnT1. (2024). https://pubmed.ncbi.nlm.nih.gov/38669333/ DOI: 10.1126/sciadv.adk5128
Complete structured claim and evidence
Human ZnT1 purified with zinc at pH 6.0 yielded inward-facing, outward-facing and mixed dimers, whereas the pH 7.5 zinc-bound structure was outward-facing; the authors interpreted structures and simulations as supporting proton-dependent zinc release.
Proton → Human ZnT1 (SLC30A1) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Wild-type human ZnT1 cryo-EM, biochemical assays and molecular dynamics
exposure
Cryo-EM preparations with 1 mM zinc at pH 6.0 or pH 7.5.
limitations
Conformational snapshots and simulations do not directly quantify coupled proton flux or establish that calcium cannot couple transport. This record preserves observations and labels the interpretation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens protein
plain_language
Acidity changed the shapes captured for human ZnT1, informing one proposed export mechanism.
primary_references
[zinc-trans-39390258] Structural insights into human zinc transporter ZnT1 mediated Zn2+ efflux. (2024). https://pubmed.ncbi.nlm.nih.gov/39390258/ DOI: 10.1038/s44319-024-00287-3
tissue_or_cell_type
Detergent-solubilized purified membrane protein
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 297–308
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type human ZnT1 cryo-EM, biochemical assays and molecular dynamics · source_derived_draft · unverified_draft
### zinc-trans-znt1-low-ph-conformations Human ZnT1 purified with zinc at pH 6.0 yielded inward-facing, outward-facing and mixed dimers, whereas the pH 7.5 zinc-bound structure was outward-facing; the authors interpreted structures and simulations as supporting proton-dependent zinc release. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Acidity changed the shapes captured for human ZnT1, informing one proposed export mechanism. organism: Homo sapiens protein tissue_or_cell_type: Detergent-solubilized purified membrane protein experimental_model: Wild-type human ZnT1 cryo-EM, biochemical assays and molecular dynamics limitations: Conformational snapshots and simulations do not directly quantify coupled proton flux or establish that calcium cannot couple transport. This record preserves observations and labels the interpretation. exposure: Cryo-EM preparations with 1 mM zinc at pH 6.0 or pH 7.5. cross_nutrient: false [zinc-trans-39390258] Structural insights into human zinc transporter ZnT1 mediated Zn2+ efflux. (2024). https://pubmed.ncbi.nlm.nih.gov/39390258/ DOI: 10.1038/s44319-024-00287-3
Complete structured claim and evidence
Human ZnT2 H54R expressed in HEK293 cells accumulated in perinuclear aggresomal structures and showed reduced zinc secretion.
Human ZnT2 H54R → Cellular zinc secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
H54R expression and localization assays in HEK293 cells
exposure
H54R compared with wild-type ZnT2.
limitations
Cultured kidney-derived cells do not reproduce all lactating mammary processes; a specific variant cannot represent all maternal low-zinc milk.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A milk-zinc-associated ZnT2 variant was misplaced inside cells and exported less zinc.
primary_references
[zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200
tissue_or_cell_type
HEK293 cells; variant identified in mothers with low milk zinc
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 310–321
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · H54R expression and localization assays in HEK293 cells · source_derived_draft · unverified_draft
### zinc-trans-znt2-h54r-export Human ZnT2 H54R expressed in HEK293 cells accumulated in perinuclear aggresomal structures and showed reduced zinc secretion. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A milk-zinc-associated ZnT2 variant was misplaced inside cells and exported less zinc. organism: Homo sapiens tissue_or_cell_type: HEK293 cells; variant identified in mothers with low milk zinc experimental_model: H54R expression and localization assays in HEK293 cells limitations: Cultured kidney-derived cells do not reproduce all lactating mammary processes; a specific variant cannot represent all maternal low-zinc milk. exposure: H54R compared with wild-type ZnT2. cross_nutrient: false [zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200
Complete structured claim and evidence
Coexpressing human ZnT2 H54R with wild-type ZnT2 did not abolish the increased zinc secretion produced by wild-type ZnT2 overexpression alone.
Human ZnT2 H54R → Cellular zinc secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Wild-type/mutant coexpression in HEK293 cells
exposure
H54R plus wild type compared with wild type alone.
limitations
Negative result in an overexpression assay; it does not establish complete compensation in lactating women or the penetrance of the variant.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
In this assay, the H54R variant did not block the working ZnT2 protein.
primary_references
[zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200
tissue_or_cell_type
HEK293 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 323–334
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type/mutant coexpression in HEK293 cells · source_derived_draft · unverified_draft
### zinc-trans-znt2-h54r-coexpression Coexpressing human ZnT2 H54R with wild-type ZnT2 did not abolish the increased zinc secretion produced by wild-type ZnT2 overexpression alone. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this assay, the H54R variant did not block the working ZnT2 protein. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Wild-type/mutant coexpression in HEK293 cells limitations: Negative result in an overexpression assay; it does not establish complete compensation in lactating women or the penetrance of the variant. exposure: H54R plus wild type compared with wild type alone. cross_nutrient: false [zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200
Complete structured claim and evidence
Human ZnT2 W152R lost zinc transport activity in zinc-sensitive DT40 cells.
Human ZnT2 W152R → Vesicular zinc sequestration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human ZnT2 constructs in zinc-sensitive chicken DT40 cells; sequence reference NP_001004434
exposure
W152R compared with wild type; functional complementation and zinc-handling assays.
limitations
Model tests intrinsic variant function; DT40 survival/compartment readouts are not direct measurement of zinc secretion into human milk.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Human protein in Gallus gallus cells
plain_language
One maternal ZnT2 variant could no longer move zinc in the test cells.
primary_references
[zinc-trans-23741301] Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant. (2013). https://pubmed.ncbi.nlm.nih.gov/23741301/ DOI: 10.1371/journal.pone.0064045
tissue_or_cell_type
Engineered DT40-cell zinc compartments
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 336–347
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ZnT2 constructs in zinc-sensitive chicken DT40 cells; sequence reference NP_001004434 · source_derived_draft · unverified_draft
### zinc-trans-znt2-w152r-transport Human ZnT2 W152R lost zinc transport activity in zinc-sensitive DT40 cells. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: One maternal ZnT2 variant could no longer move zinc in the test cells. organism: Human protein in Gallus gallus cells tissue_or_cell_type: Engineered DT40-cell zinc compartments experimental_model: Human ZnT2 constructs in zinc-sensitive chicken DT40 cells; sequence reference NP_001004434 limitations: Model tests intrinsic variant function; DT40 survival/compartment readouts are not direct measurement of zinc secretion into human milk. exposure: W152R compared with wild type; functional complementation and zinc-handling assays. cross_nutrient: false [zinc-trans-23741301] Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant. (2013). https://pubmed.ncbi.nlm.nih.gov/23741301/ DOI: 10.1371/journal.pone.0064045
Complete structured claim and evidence
Human ZnT2 S296L retained zinc transport and dimer-forming capacity in the DT40 characterization but had markedly reduced protein stability.
Human ZnT2 S296L → ZnT2 protein stability source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human ZnT2 variants in zinc-sensitive DT40 cells; sequence reference NP_001004434
exposure
S296L variant compared with wild type.
limitations
Intrinsic activity and protein abundance must be separated; the variant is not described as completely transport-inactive.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Human protein in Gallus gallus cells
plain_language
Another ZnT2 variant could work when present, but was unstable.
primary_references
[zinc-trans-23741301] Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant. (2013). https://pubmed.ncbi.nlm.nih.gov/23741301/ DOI: 10.1371/journal.pone.0064045
tissue_or_cell_type
Engineered DT40 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 349–360
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ZnT2 variants in zinc-sensitive DT40 cells; sequence reference NP_001004434 · source_derived_draft · unverified_draft
### zinc-trans-znt2-s296l-stability Human ZnT2 S296L retained zinc transport and dimer-forming capacity in the DT40 characterization but had markedly reduced protein stability. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another ZnT2 variant could work when present, but was unstable. organism: Human protein in Gallus gallus cells tissue_or_cell_type: Engineered DT40 cells experimental_model: Human ZnT2 variants in zinc-sensitive DT40 cells; sequence reference NP_001004434 limitations: Intrinsic activity and protein abundance must be separated; the variant is not described as completely transport-inactive. exposure: S296L variant compared with wild type. cross_nutrient: false [zinc-trans-23741301] Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant. (2013). https://pubmed.ncbi.nlm.nih.gov/23741301/ DOI: 10.1371/journal.pone.0064045
Complete structured claim and evidence
Mouse ZIP5 expression increased cellular Zn(II) uptake and showed selectivity for zinc among the potential substrates tested.
Mouse ZIP5 (Slc39a5) → Cellular zinc influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Heterologous mouse ZIP5 expression
exposure
Expression and substrate tests; abstract does not specify concentrations.
limitations
Selectivity is bounded by the tested panel and assay; this cannot exclude every other substrate in other systems.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in cultured cells
plain_language
Mouse ZIP5 can move zinc into cells.
primary_references
[zinc-trans-15322118] The mammalian Zip5 protein is a zinc transporter that localizes to the basolateral surface of polarized cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15322118/ DOI: 10.1074/jbc.m408361200
tissue_or_cell_type
Cultured-cell plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 362–373
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous mouse ZIP5 expression · source_derived_draft · unverified_draft
### zinc-trans-zip5-influx Mouse ZIP5 expression increased cellular Zn(II) uptake and showed selectivity for zinc among the potential substrates tested. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse ZIP5 can move zinc into cells. organism: Mouse protein in cultured cells tissue_or_cell_type: Cultured-cell plasma membrane experimental_model: Heterologous mouse ZIP5 expression limitations: Selectivity is bounded by the tested panel and assay; this cannot exclude every other substrate in other systems. exposure: Expression and substrate tests; abstract does not specify concentrations. cross_nutrient: false [zinc-trans-15322118] The mammalian Zip5 protein is a zinc transporter that localizes to the basolateral surface of polarized cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15322118/ DOI: 10.1074/jbc.m408361200
Complete structured claim and evidence
Mouse ZIP5 localized to the basolateral membrane when expressed in polarized MDCK cells.
Mouse ZIP5 (Slc39a5) → Polarized epithelial basolateral membrane source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Polarized Madin-Darby canine kidney cells expressing mouse ZIP5
exposure
Polarized-cell localization assay.
limitations
Localization supports a directional hypothesis but does not itself measure net intestinal zinc excretion or demonstrate human renal zinc reabsorption.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in Canis lupus familiaris cells
plain_language
In polarized kidney-derived cells, ZIP5 sat on the side facing the tissue rather than the lumen.
primary_references
[zinc-trans-15322118] The mammalian Zip5 protein is a zinc transporter that localizes to the basolateral surface of polarized cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15322118/ DOI: 10.1074/jbc.m408361200
tissue_or_cell_type
MDCK epithelial basolateral membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 375–386
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized Madin-Darby canine kidney cells expressing mouse ZIP5 · source_derived_draft · unverified_draft
### zinc-trans-zip5-basolateral Mouse ZIP5 localized to the basolateral membrane when expressed in polarized MDCK cells. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: In polarized kidney-derived cells, ZIP5 sat on the side facing the tissue rather than the lumen. organism: Mouse protein in Canis lupus familiaris cells tissue_or_cell_type: MDCK epithelial basolateral membrane experimental_model: Polarized Madin-Darby canine kidney cells expressing mouse ZIP5 limitations: Localization supports a directional hypothesis but does not itself measure net intestinal zinc excretion or demonstrate human renal zinc reabsorption. exposure: Polarized-cell localization assay. cross_nutrient: false [zinc-trans-15322118] The mammalian Zip5 protein is a zinc transporter that localizes to the basolateral surface of polarized cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15322118/ DOI: 10.1074/jbc.m408361200
Complete structured claim and evidence
Enterocyte-specific Zip5 deletion increased pancreatic zinc in mice eating a zinc-adequate diet.
Mouse enterocyte-specific Slc39a5 knockout genotype → Pancreatic total zinc content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Conditional intestinal knockout with tissue elemental analysis
exposure
Induced enterocyte deletion on zinc-adequate chow.
limitations
This measured redistribution supports but does not directly quantify the proposed blood-to-enterocyte-to-lumen excretion route.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Removing intestinal ZIP5 changed where zinc accumulated, increasing the pancreatic pool.
primary_references
[zinc-trans-24303081] The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and protects the pancreas against zinc toxicity. (2013). https://pubmed.ncbi.nlm.nih.gov/24303081/ DOI: 10.1371/journal.pone.0082149
tissue_or_cell_type
Intestinal enterocytes; pancreatic zinc endpoint
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 388–399
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal knockout with tissue elemental analysis · source_derived_draft · unverified_draft
### zinc-trans-intestinal-zip5-pancreas-zinc Enterocyte-specific Zip5 deletion increased pancreatic zinc in mice eating a zinc-adequate diet. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing intestinal ZIP5 changed where zinc accumulated, increasing the pancreatic pool. organism: Mus musculus tissue_or_cell_type: Intestinal enterocytes; pancreatic zinc endpoint experimental_model: Conditional intestinal knockout with tissue elemental analysis limitations: This measured redistribution supports but does not directly quantify the proposed blood-to-enterocyte-to-lumen excretion route. exposure: Induced enterocyte deletion on zinc-adequate chow. cross_nutrient: false [zinc-trans-24303081] The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and protects the pancreas against zinc toxicity. (2013). https://pubmed.ncbi.nlm.nih.gov/24303081/ DOI: 10.1371/journal.pone.0082149
Complete structured claim and evidence
Pancreatic acinar-cell Zip5 deletion impaired retention of administered 67Zn despite no detected impairment of rapid pancreatic 67Zn accumulation.
Mouse pancreatic acinar Slc39a5 knockout genotype → Pancreatic zinc retention source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Acinar-cell-specific knockout and 67Zn tracer kinetics
exposure
Tracer zinc uptake and retention compared between acinar knockouts and controls.
limitations
The negative acute-uptake result is retained; retention differences do not identify every influx or efflux pathway.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Pancreatic ZIP5 helped retain zinc after uptake, rather than being required for the initial uptake measured here.
primary_references
[zinc-trans-24303081] The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and protects the pancreas against zinc toxicity. (2013). https://pubmed.ncbi.nlm.nih.gov/24303081/ DOI: 10.1371/journal.pone.0082149
tissue_or_cell_type
Pancreatic acinar cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 401–412
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acinar-cell-specific knockout and 67Zn tracer kinetics · source_derived_draft · unverified_draft
### zinc-trans-pancreas-zip5-retention Pancreatic acinar-cell Zip5 deletion impaired retention of administered 67Zn despite no detected impairment of rapid pancreatic 67Zn accumulation. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pancreatic ZIP5 helped retain zinc after uptake, rather than being required for the initial uptake measured here. organism: Mus musculus tissue_or_cell_type: Pancreatic acinar cells experimental_model: Acinar-cell-specific knockout and 67Zn tracer kinetics limitations: The negative acute-uptake result is retained; retention differences do not identify every influx or efflux pathway. exposure: Tracer zinc uptake and retention compared between acinar knockouts and controls. cross_nutrient: false [zinc-trans-24303081] The zinc transporter Zip5 (Slc39a5) regulates intestinal zinc excretion and protects the pancreas against zinc toxicity. (2013). https://pubmed.ncbi.nlm.nih.gov/24303081/ DOI: 10.1371/journal.pone.0082149
Complete structured claim and evidence
During dietary zinc deficiency in mice, ZIP5 protein was internalized and degraded in enterocytes, pancreatic acinar cells and visceral endoderm even though Zip5 mRNA abundance did not change.
Zinc → ZIP5 protein abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Dietary depletion/repletion and protein/RNA assays
exposure
Defined zinc-deficient diet followed in some experiments by oral zinc repletion.
limitations
Protein abundance, transcription and transport flux are different endpoints; this is a mouse dietary adaptation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Zinc deficiency reduced ZIP5 protein without reducing its messenger RNA.
primary_references
[zinc-trans-18020946] Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5). (2007). https://pubmed.ncbi.nlm.nih.gov/18020946/ DOI: 10.1515/bc.2007.149
tissue_or_cell_type
Enterocytes, acinar cells and visceral endoderm
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 414–425
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary depletion/repletion and protein/RNA assays · source_derived_draft · unverified_draft
### zinc-trans-zip5-diet-deficiency During dietary zinc deficiency in mice, ZIP5 protein was internalized and degraded in enterocytes, pancreatic acinar cells and visceral endoderm even though Zip5 mRNA abundance did not change. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc deficiency reduced ZIP5 protein without reducing its messenger RNA. organism: Mus musculus tissue_or_cell_type: Enterocytes, acinar cells and visceral endoderm experimental_model: Dietary depletion/repletion and protein/RNA assays limitations: Protein abundance, transcription and transport flux are different endpoints; this is a mouse dietary adaptation. exposure: Defined zinc-deficient diet followed in some experiments by oral zinc repletion. cross_nutrient: false [zinc-trans-18020946] Novel zinc-responsive post-transcriptional mechanisms reciprocally regulate expression of the mouse Slc39a4 and Slc39a5 zinc transporters (Zip4 and Zip5). (2007). https://pubmed.ncbi.nlm.nih.gov/18020946/ DOI: 10.1515/bc.2007.149
Complete structured claim and evidence
Rat ZIP8 expression in HEK293T cells increased radiolabeled zinc uptake by about 40% compared with empty-vector controls.
Rat ZIP8 (Slc39a8) → Cellular zinc influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Rat ZIP8 transfection and 65Zn uptake
exposure
2 micromolar radiolabeled zinc for 1 hour, 48 hours after transfection.
limitations
Overexpression effect; it does not quantify native human tissue flux.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rat protein in human HEK293T cells
plain_language
Rat ZIP8 increased zinc entry when expressed in human-derived cells.
primary_references
[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
tissue_or_cell_type
Cultured-cell plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 427–438
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat ZIP8 transfection and 65Zn uptake · source_derived_draft · unverified_draft
### zinc-trans-zip8-zinc-influx Rat ZIP8 expression in HEK293T cells increased radiolabeled zinc uptake by about 40% compared with empty-vector controls. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Rat ZIP8 increased zinc entry when expressed in human-derived cells. organism: Rat protein in human HEK293T cells tissue_or_cell_type: Cultured-cell plasma membrane experimental_model: Rat ZIP8 transfection and 65Zn uptake limitations: Overexpression effect; it does not quantify native human tissue flux. exposure: 2 micromolar radiolabeled zinc for 1 hour, 48 hours after transfection. cross_nutrient: false [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
Complete structured claim and evidence
A tenfold molar excess of iron inhibited radiolabeled zinc uptake in HEK293T cells expressing rat ZIP8.
Ferrous iron → Cellular zinc influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Rat ZIP8-expressing HEK293T radiotracer assay
exposure
2 micromolar labeled zinc and tenfold unlabeled iron excess; uptake medium included ascorbate.
limitations
Transport competition in cells is not a universal dietary zinc/iron ratio or a prediction for mixed meals.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rat protein in human cells
plain_language
Iron reduced zinc entry through this transporter system under the tested culture conditions.
primary_references
[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
tissue_or_cell_type
HEK293T cells
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 440–451
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat ZIP8-expressing HEK293T radiotracer assay · source_derived_draft · unverified_draft
### zinc-trans-zip8-iron-inhibits-zinc A tenfold molar excess of iron inhibited radiolabeled zinc uptake in HEK293T cells expressing rat ZIP8. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron reduced zinc entry through this transporter system under the tested culture conditions. organism: Rat protein in human cells tissue_or_cell_type: HEK293T cells experimental_model: Rat ZIP8-expressing HEK293T radiotracer assay limitations: Transport competition in cells is not a universal dietary zinc/iron ratio or a prediction for mixed meals. exposure: 2 micromolar labeled zinc and tenfold unlabeled iron excess; uptake medium included ascorbate. cross_nutrient: true [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
Complete structured claim and evidence
A tenfold molar excess of zinc inhibited iron uptake by more than 90% in rat ZIP8-expressing HEK293T cells under the study conditions.
Zinc(II) ion → Cellular iron uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Rat ZIP8-expressing HEK293T radiotracer assay
exposure
2 micromolar labeled iron with ascorbate and tenfold unlabeled zinc excess.
limitations
The assay contains reduction chemistry and soluble ions; this is not direct evidence for the magnitude of human meal-iron inhibition.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rat protein in human cells
plain_language
Zinc strongly reduced iron entry in this cultured transport system.
primary_references
[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
tissue_or_cell_type
HEK293T cells
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 453–464
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat ZIP8-expressing HEK293T radiotracer assay · source_derived_draft · unverified_draft
### zinc-trans-zip8-zinc-inhibits-iron A tenfold molar excess of zinc inhibited iron uptake by more than 90% in rat ZIP8-expressing HEK293T cells under the study conditions. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc strongly reduced iron entry in this cultured transport system. organism: Rat protein in human cells tissue_or_cell_type: HEK293T cells experimental_model: Rat ZIP8-expressing HEK293T radiotracer assay limitations: The assay contains reduction chemistry and soluble ions; this is not direct evidence for the magnitude of human meal-iron inhibition. exposure: 2 micromolar labeled iron with ascorbate and tenfold unlabeled zinc excess. cross_nutrient: true [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
Complete structured claim and evidence
Suppressing endogenous human ZIP8 in BeWo placental cells reduced iron uptake by approximately 40%.
Human ZIP8 (SLC39A8) → Placental-cell iron uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
experimental_model
ZIP8 suppression in BeWo trophoblast-derived cells
exposure
Endogenous ZIP8 knockdown compared with controls.
limitations
This is iron uptake in a placental cell line, not direct transplacental zinc flux or an in vivo fetal iron requirement for dietary zinc.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
ZIP8 contributed to iron entry in a human placental cell model.
primary_references
[zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
tissue_or_cell_type
BeWo placental cell line
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 466–477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ZIP8 suppression in BeWo trophoblast-derived cells · source_derived_draft · unverified_draft
### zinc-trans-zip8-placental-iron Suppressing endogenous human ZIP8 in BeWo placental cells reduced iron uptake by approximately 40%. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: ZIP8 contributed to iron entry in a human placental cell model. organism: Homo sapiens tissue_or_cell_type: BeWo placental cell line experimental_model: ZIP8 suppression in BeWo trophoblast-derived cells limitations: This is iron uptake in a placental cell line, not direct transplacental zinc flux or an in vivo fetal iron requirement for dietary zinc. exposure: Endogenous ZIP8 knockdown compared with controls. cross_nutrient: true [zinc-trans-22898811] ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. (2012). https://pubmed.ncbi.nlm.nih.gov/22898811/ DOI: 10.1074/jbc.m112.367284
Complete structured claim and evidence
Mouse ZIP14 expression in Xenopus oocytes supported saturable zinc uptake with an apparent half-maximal zinc concentration near 2 micromolar.
Mouse ZIP14 (Slc39a14) → Cellular zinc influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
RNA-injected Xenopus oocytes and 65Zn uptake
exposure
Zinc concentration-response curve under the study transport conditions.
limitations
The apparent affinity belongs to this assay, not a serum zinc cutoff; protein is the mouse ortholog.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in Xenopus laevis oocytes
plain_language
Mouse ZIP14 directly carried zinc in the oocyte assay.
primary_references
[zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 479–490
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RNA-injected Xenopus oocytes and 65Zn uptake · source_derived_draft · unverified_draft
### zinc-trans-zip14-zinc-influx Mouse ZIP14 expression in Xenopus oocytes supported saturable zinc uptake with an apparent half-maximal zinc concentration near 2 micromolar. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse ZIP14 directly carried zinc in the oocyte assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: RNA-injected Xenopus oocytes and 65Zn uptake limitations: The apparent affinity belongs to this assay, not a serum zinc cutoff; protein is the mouse ortholog. exposure: Zinc concentration-response curve under the study transport conditions. cross_nutrient: false [zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
Mouse ZIP14 directly mediated 54Mn(II) uptake in RNA-injected Xenopus oocytes.
Mouse ZIP14 (Slc39a14) → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
RNA-injected Xenopus oocytes with radiolabeled metal uptake
exposure
54Mn transport compared with uninjected controls.
limitations
Transport capacity is not proof that manganese supplements improve zinc transport or vice versa.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in Xenopus laevis oocytes
plain_language
ZIP14 could carry manganese as well as zinc in this experiment.
primary_references
[zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 492–503
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RNA-injected Xenopus oocytes with radiolabeled metal uptake · source_derived_draft · unverified_draft
### zinc-trans-zip14-manganese-influx Mouse ZIP14 directly mediated 54Mn(II) uptake in RNA-injected Xenopus oocytes. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: ZIP14 could carry manganese as well as zinc in this experiment. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: RNA-injected Xenopus oocytes with radiolabeled metal uptake limitations: Transport capacity is not proof that manganese supplements improve zinc transport or vice versa. exposure: 54Mn transport compared with uninjected controls. cross_nutrient: true [zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
Zinc inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes.
Zinc(II) ion → Cellular iron uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Mouse ZIP14 in Xenopus oocytes
exposure
Radiolabeled ferrous iron uptake with competing zinc.
limitations
Ferrous and ferric iron are distinct. This competition does not establish in vivo dietary interactions; transport properties vary by substrate.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in Xenopus laevis oocytes
plain_language
Zinc interfered with ferrous iron entry through ZIP14 in the transport assay.
primary_references
[zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 505–516
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse ZIP14 in Xenopus oocytes · source_derived_draft · unverified_draft
### zinc-trans-zip14-zinc-inhibits-iron Zinc inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc interfered with ferrous iron entry through ZIP14 in the transport assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Mouse ZIP14 in Xenopus oocytes limitations: Ferrous and ferric iron are distinct. This competition does not establish in vivo dietary interactions; transport properties vary by substrate. exposure: Radiolabeled ferrous iron uptake with competing zinc. cross_nutrient: true [zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
Mouse ZIP14 did not increase uptake of radiolabeled copper supplied as Cu(I) or Cu(II) in the tested oocyte conditions.
Mouse ZIP14 (Slc39a14) → Cellular copper uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Radiolabeled Cu(I) and Cu(II) uptake in Xenopus oocytes
exposure
Cu(I) and Cu(II) tested separately against controls.
limitations
A bounded negative result does not mean zinc and copper have no interaction through other proteins or intestinal mechanisms.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in Xenopus laevis oocytes
plain_language
This ZIP14 experiment found no copper transport despite detecting other metal substrates.
primary_references
[zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 518–529
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled Cu(I) and Cu(II) uptake in Xenopus oocytes · source_derived_draft · unverified_draft
### zinc-trans-zip14-copper-negative Mouse ZIP14 did not increase uptake of radiolabeled copper supplied as Cu(I) or Cu(II) in the tested oocyte conditions. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: This ZIP14 experiment found no copper transport despite detecting other metal substrates. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Radiolabeled Cu(I) and Cu(II) uptake in Xenopus oocytes limitations: A bounded negative result does not mean zinc and copper have no interaction through other proteins or intestinal mechanisms. exposure: Cu(I) and Cu(II) tested separately against controls. cross_nutrient: true [zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
ZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells.
Mouse ZIP8 (Slc39a8) → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Polarized proximal-tubule culture with separately accessible apical and basolateral compartments
exposure
ZIP8 siRNA versus controls during apical manganese exposure.
limitations
This is manganese uptake, not direct proof of zinc reabsorption by ZIP8; ZIP14 and DMT1 knockdowns also affected uptake in the paper.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side.
primary_references
[zinc-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
tissue_or_cell_type
Mouse proximal-tubule epithelial cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 531–542
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized proximal-tubule culture with separately accessible apical and basolateral compartments · source_derived_draft · unverified_draft
### zinc-trans-renal-zip8-manganese ZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side. organism: Mus musculus tissue_or_cell_type: Mouse proximal-tubule epithelial cells experimental_model: Polarized proximal-tubule culture with separately accessible apical and basolateral compartments limitations: This is manganese uptake, not direct proof of zinc reabsorption by ZIP8; ZIP14 and DMT1 knockdowns also affected uptake in the paper. exposure: ZIP8 siRNA versus controls during apical manganese exposure. cross_nutrient: true [zinc-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
Complete structured claim and evidence
Placental ZnT1 expression was lower in pregnant mice fed 15 mg zinc/kg diet than in those fed 50 mg/kg; the mRNA pattern was reflected at the protein level.
Zinc → Placental ZnT1 abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Controlled pregnancy diets and placental RNA/protein assays
exposure
15 versus 50 mg zinc/kg diet from pregnancy onset to day 17; 150 mg/kg group also had lower expression than 50 mg/kg.
limitations
Nonmonotonic expression must not be converted into a monotonic transport-flux model. These mouse diets are not human dose instructions or serum thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Moderately restricting maternal dietary zinc lowered placental ZnT1 in mice.
primary_references
[zinc-trans-16914197] Zinc transporters in the mouse placenta show a coordinated regulatory response to changes in dietary zinc intake. (2007). https://pubmed.ncbi.nlm.nih.gov/16914197/ DOI: 10.1016/j.placenta.2006.07.002
tissue_or_cell_type
Placenta
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 544–555
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled pregnancy diets and placental RNA/protein assays · source_derived_draft · unverified_draft
### zinc-trans-placenta-znt1-restriction Placental ZnT1 expression was lower in pregnant mice fed 15 mg zinc/kg diet than in those fed 50 mg/kg; the mRNA pattern was reflected at the protein level. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Moderately restricting maternal dietary zinc lowered placental ZnT1 in mice. organism: Mus musculus tissue_or_cell_type: Placenta experimental_model: Controlled pregnancy diets and placental RNA/protein assays limitations: Nonmonotonic expression must not be converted into a monotonic transport-flux model. These mouse diets are not human dose instructions or serum thresholds. exposure: 15 versus 50 mg zinc/kg diet from pregnancy onset to day 17; 150 mg/kg group also had lower expression than 50 mg/kg. cross_nutrient: false [zinc-trans-16914197] Zinc transporters in the mouse placenta show a coordinated regulatory response to changes in dietary zinc intake. (2007). https://pubmed.ncbi.nlm.nih.gov/16914197/ DOI: 10.1016/j.placenta.2006.07.002
Complete structured claim and evidence
In the reported family, two exclusively breastfed infants developed zinc deficiency associated with low maternal milk zinc; affected mothers carried SLC30A2 H54R.
Human ZnT2 (SLC30A2) → Breast-milk zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Maternal zinc secretion determines a source of infant zinc supply.
evidence_span
{"source_cache": "artifacts/zinc-transport-sources/17065149-abstract.txt", "locator": "Primary indexed abstract; case results", "file_sha256": "a10d24cc13794e7cda0ab3553fa7b351c4f2faa583c78331b96f96edfacbe9d1"}
experimental_model
Human mother–infant clinical genetic observations
exposure
Naturally occurring maternal SLC30A2 variants; exclusive breastfeeding in the reported case setting.
limitations
Small family/case evidence does not establish population frequency or penetrance. Molecular cell assays are separate linked claims; maternal supplementation response is not inferred for these individuals from introductory background.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A maternal transport variant was linked to low milk zinc and infant deficiency.
primary_references
[zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200
tissue_or_cell_type
Maternal milk and breastfed infant
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 557–569
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human mother–infant clinical genetic observations · source_derived_draft · unverified_draft
### zinc-trans-milk-h54r-family In the reported family, two exclusively breastfed infants developed zinc deficiency associated with low maternal milk zinc; affected mothers carried SLC30A2 H54R. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A maternal transport variant was linked to low milk zinc and infant deficiency. organism: Homo sapiens tissue_or_cell_type: Maternal milk and breastfed infant experimental_model: Human mother–infant clinical genetic observations limitations: Small family/case evidence does not establish population frequency or penetrance. Molecular cell assays are separate linked claims; maternal supplementation response is not inferred for these individuals from introductory background. exposure: Naturally occurring maternal SLC30A2 variants; exclusive breastfeeding in the reported case setting. cross_nutrient: Maternal zinc secretion determines a source of infant zinc supply. evidence_span: {"source_cache": "artifacts/zinc-transport-sources/17065149-abstract.txt", "locator": "Primary indexed abstract; case results", "file_sha256": "a10d24cc13794e7cda0ab3553fa7b351c4f2faa583c78331b96f96edfacbe9d1"} [zinc-trans-17065149] Identification of a mutation in SLC30A2 (ZnT-2) in women with low milk zinc concentration that results in transient neonatal zinc deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/17065149/ DOI: 10.1074/jbc.m605821200
Complete structured claim and evidence
A mother carrying W152R and S296L on different SLC30A2 alleles had a reported greater-than-90% reduction in milk zinc; her breastfed infant developed severe zinc deficiency.
Human ZnT2 (SLC30A2) → Breast-milk zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Maternal zinc secretion determines a source of infant zinc supply.
evidence_span
{"source_cache": "artifacts/zinc-transport-sources/23741301-abstract.txt", "locator": "Primary indexed abstract; case results", "file_sha256": "b422d27e8731293ae1597e65a72d9a6f6c1a161b7adaff3f114ee23f0e95408a"}
experimental_model
Human mother–infant clinical genetic observations
exposure
Naturally occurring maternal SLC30A2 variants; exclusive breastfeeding in the reported case setting.
limitations
Small family/case evidence does not establish population frequency or penetrance. Molecular cell assays are separate linked claims; maternal supplementation response is not inferred for these individuals from introductory background.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Two different maternal variants were linked to profoundly low milk zinc.
primary_references
[zinc-trans-23741301] Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant. (2013). https://pubmed.ncbi.nlm.nih.gov/23741301/ DOI: 10.1371/journal.pone.0064045
tissue_or_cell_type
Maternal milk and breastfed infant
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 571–583
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human mother–infant clinical genetic observations · source_derived_draft · unverified_draft
### zinc-trans-milk-compound-variants A mother carrying W152R and S296L on different SLC30A2 alleles had a reported greater-than-90% reduction in milk zinc; her breastfed infant developed severe zinc deficiency. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two different maternal variants were linked to profoundly low milk zinc. organism: Homo sapiens tissue_or_cell_type: Maternal milk and breastfed infant experimental_model: Human mother–infant clinical genetic observations limitations: Small family/case evidence does not establish population frequency or penetrance. Molecular cell assays are separate linked claims; maternal supplementation response is not inferred for these individuals from introductory background. exposure: Naturally occurring maternal SLC30A2 variants; exclusive breastfeeding in the reported case setting. cross_nutrient: Maternal zinc secretion determines a source of infant zinc supply. evidence_span: {"source_cache": "artifacts/zinc-transport-sources/23741301-abstract.txt", "locator": "Primary indexed abstract; case results", "file_sha256": "b422d27e8731293ae1597e65a72d9a6f6c1a161b7adaff3f114ee23f0e95408a"} [zinc-trans-23741301] Compound heterozygous mutations in SLC30A2/ZnT2 results in low milk zinc concentrations: a novel mechanism for zinc deficiency in a breast-fed infant. (2013). https://pubmed.ncbi.nlm.nih.gov/23741301/ DOI: 10.1371/journal.pone.0064045
Complete structured claim and evidence
After enterocyte Zip4 deletion in mice, liver iron, manganese and copper gradually accumulated as the zinc-depletion disease progressed.
Mouse enterocyte-specific Slc39a4 knockout genotype → Hepatic iron, manganese and copper accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
evidence_span
{"source_cache": "artifacts/zinc-transport-sources/22737083-abstract.txt", "locator": "Primary indexed abstract; tissue elemental analysis", "file_sha256": "4643d3986c556a001c45365febbb07095bcdc8bc604e30488d3fb98a23511a4b"}
experimental_model
Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis
exposure
Conditional gene deletion compared with intact controls.
limitations
A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc. Tissue accumulation is not proof of systemic nutritional adequacy of the other metals.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Loss of zinc uptake disrupted the distribution of several other metals.
primary_references
[zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766
tissue_or_cell_type
Small intestine, liver, pancreas
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 585–597
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis · source_derived_draft · unverified_draft
### zinc-trans-zip4-other-metals After enterocyte Zip4 deletion in mice, liver iron, manganese and copper gradually accumulated as the zinc-depletion disease progressed. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of zinc uptake disrupted the distribution of several other metals. organism: Mus musculus tissue_or_cell_type: Small intestine, liver, pancreas experimental_model: Tamoxifen-inducible enterocyte-specific knockout and tissue elemental analysis limitations: A genetic transport defect is not interchangeable with low intake. Total tissue zinc does not resolve labile versus protein-bound zinc. Tissue accumulation is not proof of systemic nutritional adequacy of the other metals. exposure: Conditional gene deletion compared with intact controls. cross_nutrient: false evidence_span: {"source_cache": "artifacts/zinc-transport-sources/22737083-abstract.txt", "locator": "Primary indexed abstract; tissue elemental analysis", "file_sha256": "4643d3986c556a001c45365febbb07095bcdc8bc604e30488d3fb98a23511a4b"} [zinc-trans-22737083] A mouse model of acrodermatitis enteropathica: loss of intestine zinc transporter ZIP4 (Slc39a4) disrupts the stem cell niche and intestine integrity. (2012). https://pubmed.ncbi.nlm.nih.gov/22737083/ DOI: 10.1371/journal.pgen.1002766
Complete structured claim and evidence
Chelating zinc from recombinant human CA2 reduced catalytic activity; the apo preparation retained about 10% residual zinc.
Zinc-depleted human CA2 prepared by chelation → Human carbonic anhydrase II / CA2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange
exposure
100 mM pyridine-2,6-dicarboxylic acid, 25 mM MOPS pH 7.0, 20°C for 8 h; chelator removed by buffer exchange.
limitations
Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Removing the bound zinc largely disables CA2, even though the protein is still present.
primary_references
[zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 599–610
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange · source_derived_draft · unverified_draft
### zinc-enz-ca2-removal Chelating zinc from recombinant human CA2 reduced catalytic activity; the apo preparation retained about 10% residual zinc. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the bound zinc largely disables CA2, even though the protein is still present. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange limitations: Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation. exposure: 100 mM pyridine-2,6-dicarboxylic acid, 25 mM MOPS pH 7.0, 20°C for 8 h; chelator removed by buffer exchange. cross_nutrient: false [zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
Complete structured claim and evidence
Adding 1 mM ZnCl2 revived the activity of chelated recombinant human CA2.
Zinc(II) ion → Zinc-depleted human CA2 prepared by chelation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange
exposure
1 mM ZnCl2 added in vitro after chelation and buffer exchange.
limitations
Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation. The assay addition is not a supplement dose.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Returning zinc to the depleted enzyme restored activity.
primary_references
[zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 612–623
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange · source_derived_draft · unverified_draft
### zinc-enz-ca2-reconstitution Adding 1 mM ZnCl2 revived the activity of chelated recombinant human CA2. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Returning zinc to the depleted enzyme restored activity. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange limitations: Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation. The assay addition is not a supplement dose. exposure: 1 mM ZnCl2 added in vitro after chelation and buffer exchange. cross_nutrient: false [zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
Complete structured claim and evidence
Zinc-containing CA2 unfolded at 59±0.5°C versus 51±0.5°C for the chelated preparation in differential scanning calorimetry.
Zinc(II) ion → Thermal stability of human CA2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange
exposure
Purified apo and holo proteins; DSC in 50 mM Tris-HCl pH 7.0.
limitations
Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation. Thermal unfolding temperature is not a body-temperature requirement.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Bound zinc also helps CA2 resist thermal unfolding.
primary_references
[zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 625–636
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange · source_derived_draft · unverified_draft
### zinc-enz-ca2-stability Zinc-containing CA2 unfolded at 59±0.5°C versus 51±0.5°C for the chelated preparation in differential scanning calorimetry. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bound zinc also helps CA2 resist thermal unfolding. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange limitations: Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation. Thermal unfolding temperature is not a body-temperature requirement. exposure: Purified apo and holo proteins; DSC in 50 mM Tris-HCl pH 7.0. cross_nutrient: false [zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
Complete structured claim and evidence
The chelated human CA2 structure retained the overall protein fold relative to zinc-containing CA2.
Zinc-depleted human CA2 prepared by chelation → Human CA2 overall protein fold source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange
exposure
Chelated CA2 crystallography at 1.26 Å resolution.
limitations
Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
An enzyme can lose activity before its entire shape collapses.
primary_references
[zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 638–649
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange · source_derived_draft · unverified_draft
### zinc-enz-ca2-fold-preserved The chelated human CA2 structure retained the overall protein fold relative to zinc-containing CA2. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme can lose activity before its entire shape collapses. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified recombinant human CA2 expressed in E. coli; chelation, crystallography, DSC and H/D exchange limitations: Purified recombinant protein; chelation is not dietary deficiency. Approximately 10% zinc remained in the nominal apo preparation. exposure: Chelated CA2 crystallography at 1.26 Å resolution. cross_nutrient: false [zinc-enz-ca2-apo2009] Apo-human carbonic anhydrase II revisited: implications of the loss of a metal in protein structure, stability, and solvent network. (2009). https://pubmed.ncbi.nlm.nih.gov/19583303/ DOI: 10.1021/bi9007512
Complete structured claim and evidence
X-ray absorption analysis of human CA2 supported a zinc site with three histidine nitrogen ligands and most likely one water/hydroxide oxygen ligand in both isolated and reconstituted enzyme.
Zinc(II) ion → Human carbonic anhydrase II / CA2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified recombinant human CA2; metal reconstitution, ITC and X-ray absorption spectroscopy
exposure
Zn K-edge XANES and EXAFS on isolated and zinc-reconstituted recombinant CA2.
limitations
Coordination assignment is spectroscopic; the oxygen ligand is most likely solvent-derived, not an independently measured dietary effect.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
CA2 holds zinc with three histidines and a water-derived ligand at its active site.
primary_references
[zinc-enz-ca2-coordination2012] Revisiting zinc coordination in human carbonic anhydrase II. (2012). https://pubmed.ncbi.nlm.nih.gov/23030313/ DOI: 10.1021/ic301645j
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 651–662
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human CA2; metal reconstitution, ITC and X-ray absorption spectroscopy · source_derived_draft · unverified_draft
### zinc-enz-ca2-coordination X-ray absorption analysis of human CA2 supported a zinc site with three histidine nitrogen ligands and most likely one water/hydroxide oxygen ligand in both isolated and reconstituted enzyme. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: CA2 holds zinc with three histidines and a water-derived ligand at its active site. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified recombinant human CA2; metal reconstitution, ITC and X-ray absorption spectroscopy limitations: Coordination assignment is spectroscopic; the oxygen ligand is most likely solvent-derived, not an independently measured dietary effect. exposure: Zn K-edge XANES and EXAFS on isolated and zinc-reconstituted recombinant CA2. cross_nutrient: false [zinc-enz-ca2-coordination2012] Revisiting zinc coordination in human carbonic anhydrase II. (2012). https://pubmed.ncbi.nlm.nih.gov/23030313/ DOI: 10.1021/ic301645j
Complete structured claim and evidence
Purified human salivary and milk CA6 catalyzed CO2 hydration, with reported kcat values of 3.3×10^5 and 2.3×10^5 s−1, respectively.
Human carbonic anhydrase VI / CA6 → Bicarbonate ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology
exposure
Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk.
limitations
Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate.
primary_references
[zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9
tissue_or_cell_type
Human saliva and breast milk; purified enzyme assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 664–675
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology · source_derived_draft · unverified_draft
### zinc-enz-ca6-hydration Purified human salivary and milk CA6 catalyzed CO2 hydration, with reported kcat values of 3.3×10^5 and 2.3×10^5 s−1, respectively. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate. organism: Homo sapiens tissue_or_cell_type: Human saliva and breast milk; purified enzyme assay experimental_model: Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology limitations: Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations. exposure: Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk. cross_nutrient: false [zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9
Complete structured claim and evidence
Acetazolamide inhibited salivary and milk human CA6 with reported Ki values of 16 and 23 nM in the enzyme assay.
Acetazolamide → Human carbonic anhydrase VI / CA6 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology
exposure
Inhibitor dilution series in stopped-flow enzymology; not oral treatment.
limitations
Assay inhibition does not measure nutrient deficiency or treatment efficacy.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A carbonic anhydrase inhibitor blocked the purified secreted enzyme.
primary_references
[zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9
tissue_or_cell_type
Purified human saliva and milk CA6
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 677–688
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology · source_derived_draft · unverified_draft
### zinc-enz-ca6-inhibition Acetazolamide inhibited salivary and milk human CA6 with reported Ki values of 16 and 23 nM in the enzyme assay. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A carbonic anhydrase inhibitor blocked the purified secreted enzyme. organism: Homo sapiens tissue_or_cell_type: Purified human saliva and milk CA6 experimental_model: Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology limitations: Assay inhibition does not measure nutrient deficiency or treatment efficacy. exposure: Inhibitor dilution series in stopped-flow enzymology; not oral treatment. cross_nutrient: false [zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9
Complete structured claim and evidence
In the purified human protein system, CCS domain 1 was necessary for loading SOD1 with Cu(I).
Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR
exposure
Human CCS domain constructs and SOD1; ESI-MS and NMR.
limitations
Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
SOD1 needs copper delivery as well as zinc binding.
primary_references
[zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 690–701
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft
### zinc-enz-ccs-copper In the purified human protein system, CCS domain 1 was necessary for loading SOD1 with Cu(I). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 needs copper delivery as well as zinc binding. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Human CCS domain constructs and SOD1; ESI-MS and NMR. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
Complete structured claim and evidence
Human CCS domain 2 promoted the CCS-SOD1 heterodimer interaction required for copper loading in the in-vitro study.
Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR
exposure
Full-length and domain-truncated human CCS with human SOD1.
limitations
Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The copper-delivery protein first has to engage SOD1.
primary_references
[zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 703–714
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft
### zinc-enz-ccs-recognition Human CCS domain 2 promoted the CCS-SOD1 heterodimer interaction required for copper loading in the in-vitro study. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper-delivery protein first has to engage SOD1. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Full-length and domain-truncated human CCS with human SOD1. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
Complete structured claim and evidence
Human CCS domain 3 catalyzed formation of the SOD1 Cys57-Cys146 disulfide through a transfer mechanism involving CCS Cys244 and Cys246.
Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR
exposure
Human CCS mutants/domain constructs examined by ESI-MS and NMR.
limitations
Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
SOD1 maturation also requires forming a specific internal disulfide bond.
primary_references
[zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 716–727
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR · source_derived_draft · unverified_draft
### zinc-enz-ccs-disulfide Human CCS domain 3 catalyzed formation of the SOD1 Cys57-Cys146 disulfide through a transfer mechanism involving CCS Cys244 and Cys246. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 maturation also requires forming a specific internal disulfide bond. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Purified human SOD1 and full-length, mutant or truncated human CCS; ESI-MS and NMR limitations: Reconstituted human proteins studied in vitro; domain contributions do not imply CCS carries zinc to SOD1 or that zinc supplementation completes copper loading. exposure: Human CCS mutants/domain constructs examined by ESI-MS and NMR. cross_nutrient: true [zinc-enz-ccs-2012] Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). (2012). https://pubmed.ncbi.nlm.nih.gov/22869735/ DOI: 10.1073/pnas.1207493109
Complete structured claim and evidence
Adding 10 µM ZnSO4 during human SOD1 expression in HEK293T cells promoted site-selective binding of one zinc ion per SOD1 subunit and the zinc-containing dimer.
Zinc(II) ion → Zinc-bound disulfide-reduced human SOD1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR
exposure
10 µM ZnSO4 immediately after transfection; 48 h expression before later copper manipulations.
limitations
HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc binding helps the cellular SOD1 protein reach a dimeric maturation intermediate.
primary_references
[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
tissue_or_cell_type
Human HEK293T cytoplasm
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 729–740
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft
### zinc-enz-sod1-zinc-binding Adding 10 µM ZnSO4 during human SOD1 expression in HEK293T cells promoted site-selective binding of one zinc ion per SOD1 subunit and the zinc-containing dimer. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc binding helps the cellular SOD1 protein reach a dimeric maturation intermediate. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. exposure: 10 µM ZnSO4 immediately after transfection; 48 h expression before later copper manipulations. cross_nutrient: false [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
Complete structured claim and evidence
Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1.
Human copper chaperone for SOD1 / CCS → Human copper-zinc superoxide dismutase / SOD1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR
exposure
10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h.
limitations
HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The copper chaperone increased copper loading into zinc-containing SOD1.
primary_references
[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
tissue_or_cell_type
Human HEK293T cytoplasm
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 742–753
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft
### zinc-enz-sod1-copper-loading Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper chaperone increased copper loading into zinc-containing SOD1. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. exposure: 10 µM ZnSO4 in expression medium; 100 µM CuCl2 added after 48 h and incubated 24 h. cross_nutrient: true [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
Complete structured claim and evidence
In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading.
Human copper chaperone for SOD1 / CCS → Zinc-bound disulfide-reduced human SOD1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR
exposure
10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison.
limitations
HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
CCS can help form the SOD1 disulfide before copper is inserted.
primary_references
[zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
tissue_or_cell_type
Human HEK293T cytoplasm
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 755–766
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR · source_derived_draft · unverified_draft
### zinc-enz-sod1-disulfide-independent In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: CCS can help form the SOD1 disulfide before copper is inserted. organism: Homo sapiens tissue_or_cell_type: Human HEK293T cytoplasm experimental_model: Transient expression of human SOD1 and CCS in human HEK293T cells; in-cell NMR limitations: HEK293T cells overexpressed SOD1/CCS above endogenous levels; these medium concentrations are experimental exposures, not dietary targets. Copper transfer and disulfide oxidation need not occur in a fixed coupled step in every cellular context. This is not proof that all copper is absent from the cell. exposure: 10 µM ZnSO4 and SOD1/CCS coexpression; no added CuCl2 in this comparison. cross_nutrient: true [zinc-enz-sod1-live2013] Atomic-resolution monitoring of protein maturation in live human cells by NMR. (2013). https://pubmed.ncbi.nlm.nih.gov/23455544/ DOI: 10.1038/nchembio.1202
Complete structured claim and evidence
The ZnT5-ZnT6 and ZnT7 complexes support TNAP conversion from apoenzyme to zinc-loaded active enzyme in the early secretory pathway.
Human ZnT5-ZnT6 heterodimer → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation
exposure
ZnT gene disruption and transporter re-expression comparisons.
limitations
Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Gallus gallus cell model with human proteins
plain_language
Specific transporter complexes deliver zinc while TNAP matures.
primary_references
[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
tissue_or_cell_type
Chicken DT40 early secretory pathway; human transporter complementation
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 768–779
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation · source_derived_draft · unverified_draft
### zinc-enz-znt-specific-maturation The ZnT5-ZnT6 and ZnT7 complexes support TNAP conversion from apoenzyme to zinc-loaded active enzyme in the early secretory pathway. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Specific transporter complexes deliver zinc while TNAP matures. organism: Gallus gallus cell model with human proteins tissue_or_cell_type: Chicken DT40 early secretory pathway; human transporter complementation experimental_model: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation limitations: Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred. exposure: ZnT gene disruption and transporter re-expression comparisons. cross_nutrient: false [zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
Complete structured claim and evidence
Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes.
Zinc(II) ion → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation
exposure
Genetic deficiency of the two specific secretory ZnT complexes, followed by zinc supplementation in culture; amount unreported in abstract.
limitations
Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Gallus gallus
plain_language
More available zinc did not bypass missing enzyme-loading machinery.
primary_references
[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
tissue_or_cell_type
Chicken DT40 early secretory pathway
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 781–792
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation · source_derived_draft · unverified_draft
### zinc-enz-zinc-cannot-bypass-znt-loss Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: More available zinc did not bypass missing enzyme-loading machinery. organism: Gallus gallus tissue_or_cell_type: Chicken DT40 early secretory pathway experimental_model: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation limitations: Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred. exposure: Genetic deficiency of the two specific secretory ZnT complexes, followed by zinc supplementation in culture; amount unreported in abstract. cross_nutrient: false [zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
Complete structured claim and evidence
A transport-incompetent ZnT5 variant expressed with ZnT6 stabilized TNAP protein as the apo form despite failing to restore enzyme activity.
Transport-incompetent human ZnT5 study state → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation
exposure
Transport-incompetent ZnT5 variant reconstituted with ZnT6 in DT40 cells.
limitations
Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Gallus gallus cell model with human proteins
plain_language
The transporter complex can protect the unfinished protein even when zinc transport fails.
primary_references
[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
tissue_or_cell_type
Chicken DT40 early secretory pathway; human transporter complementation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 794–805
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation · source_derived_draft · unverified_draft
### zinc-enz-znt-mutant-stabilizes A transport-incompetent ZnT5 variant expressed with ZnT6 stabilized TNAP protein as the apo form despite failing to restore enzyme activity. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter complex can protect the unfinished protein even when zinc transport fails. organism: Gallus gallus cell model with human proteins tissue_or_cell_type: Chicken DT40 early secretory pathway; human transporter complementation experimental_model: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation limitations: Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred. exposure: Transport-incompetent ZnT5 variant reconstituted with ZnT6 in DT40 cells. cross_nutrient: false [zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
Complete structured claim and evidence
Reconstitution of ZnT5-ZnT6 with transport-incompetent ZnT5 did not restore TNAP activity.
Transport-incompetent human ZnT5 study state → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation
exposure
Transport-incompetent ZnT5 variant with ZnT6, compared with functional loading machinery.
limitations
Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Gallus gallus cell model with human proteins
plain_language
Protecting the enzyme protein is insufficient when the complex cannot deliver zinc.
primary_references
[zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
tissue_or_cell_type
Chicken DT40 early secretory pathway
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 807–818
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation · source_derived_draft · unverified_draft
### zinc-enz-znt-mutant-no-activity Reconstitution of ZnT5-ZnT6 with transport-incompetent ZnT5 did not restore TNAP activity. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protecting the enzyme protein is insufficient when the complex cannot deliver zinc. organism: Gallus gallus cell model with human proteins tissue_or_cell_type: Chicken DT40 early secretory pathway experimental_model: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation limitations: Primary abstract-level evidence in engineered chicken DT40 cells with transporter complementation. Not a human dietary deficiency or supplementation trial; assay exposure amounts and mutant-specific residue effects are not inferred. exposure: Transport-incompetent ZnT5 variant with ZnT6, compared with functional loading machinery. cross_nutrient: false [zinc-enz-znt-tnap2011] Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. (2011). https://pubmed.ncbi.nlm.nih.gov/21402707/ DOI: 10.1074/jbc.m111.227173
Complete structured claim and evidence
The recombinant TNAP mutant study attributed effects of disrupting calcium site M4 to protein structure rather than direct catalysis by M4-bound calcium.
Calcium ion → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution
exposure
Recombinant TNAP M4-site mutants and metal-dependent activity comparisons at pH 7.4 and 9.8.
limitations
This record states the authors’ mechanistic interpretation; existing M3 calcium substitution and Mg/Zn reconstitution claims remain unchanged. It does not imply dietary calcium is a zinc substitute.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural.
primary_references
[zinc-enz-tnap-metals2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase. (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Purified protein; cell-free assay
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 820–831
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution · source_derived_draft · unverified_draft
### zinc-enz-tnap-m4-not-catalytic The recombinant TNAP mutant study attributed effects of disrupting calcium site M4 to protein structure rather than direct catalysis by M4-bound calcium. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution limitations: This record states the authors’ mechanistic interpretation; existing M3 calcium substitution and Mg/Zn reconstitution claims remain unchanged. It does not imply dietary calcium is a zinc substitute. exposure: Recombinant TNAP M4-site mutants and metal-dependent activity comparisons at pH 7.4 and 9.8. cross_nutrient: true [zinc-enz-tnap-metals2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase. (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study.
Zinc → Extracellular B-vitamin phosphate-ester hydrolysis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets
exposure
Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract.
limitations
Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Cell species not specified in abstract
plain_language
Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins.
primary_references
[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
tissue_or_cell_type
Cultured-cell membrane lysates
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 833–844
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft
### zinc-enz-bvitamin-cell-hydrolysis Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins. organism: Cell species not specified in abstract tissue_or_cell_type: Cultured-cell membrane lysates experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. exposure: Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
Complete structured claim and evidence
Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study.
Zinc → Extracellular B-vitamin phosphate-ester hydrolysis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets
exposure
Rats fed zinc-deficient diets; dietary content and duration not available in the abstract.
limitations
Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
Dietary zinc deficiency also reduced this measured enzyme activity in rat serum.
primary_references
[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
tissue_or_cell_type
Rat serum assayed ex vivo
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 846–857
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft
### zinc-enz-bvitamin-rat-hydrolysis Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary zinc deficiency also reduced this measured enzyme activity in rat serum. organism: Rattus norvegicus tissue_or_cell_type: Rat serum assayed ex vivo experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. The abstract does not identify which vitamin-specific endpoints were measurable in rat serum. The full-text search extract specifically said rat-serum B6 hydrolysis could not be measured; no rat B6 reaction claim or PLP participant is imported. exposure: Rats fed zinc-deficient diets; dietary content and duration not available in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r
Complete structured claim and evidence
Mtf1-null mouse embryonic stem cells lacked detectable basal and zinc-induced Mt1 and Mt2 transcription.
Mouse Mtf1 loss of function → Mouse metallothionein Mt1/Mt2 transcription source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse metal-regulatory transcription factor 1 / Mtf1 (affected_machinery); Mouse metallothionein 1 / Mt1 (regulated_protein); Mouse metallothionein 2 / Mt2 (regulated_protein); Zinc(II) ion (signal)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/8026472-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "6647e4132df7d568ef07c1a33501887c1682b18442af37dbac9f390cd212fea5"}
experimental_model
Mouse embryonic stem cells lacking Mtf1
exposure
Mtf1-null versus control and restored-expression comparisons.
limitations
Genetic transcription-factor loss is not nutritional zinc deficiency.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Without the transcription factor, the cell could not activate these zinc-binding proteins.
primary_references
[zn-sig-8026472] The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression. (1994). https://pubmed.ncbi.nlm.nih.gov/8026472/ DOI: 10.1002/j.1460-2075.1994.tb06581.x
tissue_or_cell_type
Embryonic stem cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 859–871
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse embryonic stem cells lacking Mtf1 · source_derived_draft · unverified_draft
### zn-sig-mtf1-mt1 Mtf1-null mouse embryonic stem cells lacked detectable basal and zinc-induced Mt1 and Mt2 transcription. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without the transcription factor, the cell could not activate these zinc-binding proteins. organism: Mus musculus tissue_or_cell_type: Embryonic stem cells experimental_model: Mouse embryonic stem cells lacking Mtf1 limitations: Genetic transcription-factor loss is not nutritional zinc deficiency. exposure: Mtf1-null versus control and restored-expression comparisons. cross_nutrient: Mouse metal-regulatory transcription factor 1 / Mtf1 (affected_machinery); Mouse metallothionein 1 / Mt1 (regulated_protein); Mouse metallothionein 2 / Mt2 (regulated_protein); Zinc(II) ion (signal) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/8026472-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "6647e4132df7d568ef07c1a33501887c1682b18442af37dbac9f390cd212fea5"} [zn-sig-8026472] The transcription factor MTF-1 is essential for basal and heavy metal-induced metallothionein gene expression. (1994). https://pubmed.ncbi.nlm.nih.gov/8026472/ DOI: 10.1002/j.1460-2075.1994.tb06581.x
Complete structured claim and evidence
Recombinant human and mouse MTF1 required added zinc for DNA binding; among the tested transition metals, only zinc activated recombinant MTF1 binding.
Zinc(II) ion → MTF1 binding to metal-responsive DNA elements source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"}
experimental_model
Human and mouse cell extracts and recombinant MTF1
exposure
Zinc versus other tested transition metals; DNA-binding assays.
limitations
In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens; Mus musculus
plain_language
Zinc acted as a specific input to this metal-responsive transcription factor.
primary_references
[zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127
tissue_or_cell_type
Cell extracts and recombinant protein
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 873–885
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and mouse cell extracts and recombinant MTF1 · source_derived_draft · unverified_draft
### zn-sig-zinc-mtf1-binding Recombinant human and mouse MTF1 required added zinc for DNA binding; among the tested transition metals, only zinc activated recombinant MTF1 binding. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc acted as a specific input to this metal-responsive transcription factor. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Cell extracts and recombinant protein experimental_model: Human and mouse cell extracts and recombinant MTF1 limitations: In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding. exposure: Zinc versus other tested transition metals; DNA-binding assays. cross_nutrient: Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"} [zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127
Complete structured claim and evidence
Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay.
GSH → MTF1 binding to metal-responsive DNA elements source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"}
experimental_model
Human and mouse cell extracts and recombinant MTF1
exposure
Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration.
limitations
In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens; Mus musculus
plain_language
Glutathione helped preserve the zinc-dependent sensor under this chemical stress.
primary_references
[zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127
tissue_or_cell_type
Cell extracts and recombinant protein
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 887–899
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and mouse cell extracts and recombinant MTF1 · source_derived_draft · unverified_draft
### zn-sig-gsh-mtf1-protection Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione helped preserve the zinc-dependent sensor under this chemical stress. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Cell extracts and recombinant protein experimental_model: Human and mouse cell extracts and recombinant MTF1 limitations: In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding. exposure: Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration. cross_nutrient: Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"} [zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127
Complete structured claim and evidence
Rat diets with zinc up to 450 mg/kg did not change 64Cu absorption; 900 mg/kg reduced it by about 40% and increased mucosal 64Cu uptake.
Zinc → Intestinal copper absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Copper (affected_nutrient); Intestinal mucosal copper retention (increased_endpoint)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/479878-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "643b0358984f3caac8a20e3202c14a073d11ff88758c7a9637b6f8523195658b"}
experimental_model
Dietary radiotracer experiments in rats
exposure
High dietary zinc or copper and reciprocal 64Cu/65Zn absorption measurements.
limitations
High animal dietary concentrations are not human intake thresholds. Copper displacement from metallothionein was the authors’ mechanistic interpretation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
Very high zinc trapped more copper in the intestine while less was absorbed.
primary_references
[zn-sig-479878] Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat. (1979). https://pubmed.ncbi.nlm.nih.gov/479878/ DOI: 10.1016/s0162-0134(00)80054-9
tissue_or_cell_type
Small intestine
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 901–913
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary radiotracer experiments in rats · source_derived_draft · unverified_draft
### zn-sig-zinc-copper-absorption Rat diets with zinc up to 450 mg/kg did not change 64Cu absorption; 900 mg/kg reduced it by about 40% and increased mucosal 64Cu uptake. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Very high zinc trapped more copper in the intestine while less was absorbed. organism: Rattus norvegicus tissue_or_cell_type: Small intestine experimental_model: Dietary radiotracer experiments in rats limitations: High animal dietary concentrations are not human intake thresholds. Copper displacement from metallothionein was the authors’ mechanistic interpretation. exposure: High dietary zinc or copper and reciprocal 64Cu/65Zn absorption measurements. cross_nutrient: Copper (affected_nutrient); Intestinal mucosal copper retention (increased_endpoint) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/479878-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "643b0358984f3caac8a20e3202c14a073d11ff88758c7a9637b6f8523195658b"} [zn-sig-479878] Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat. (1979). https://pubmed.ncbi.nlm.nih.gov/479878/ DOI: 10.1016/s0162-0134(00)80054-9
Complete structured claim and evidence
The increased intestinal 64Cu was predominantly metallothionein-associated; the authors inferred copper displacement of zinc after zinc-induced metallothionein synthesis.
Zinc → Rat intestinal metallothioneins measured without isoform resolution source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Copper (retained_nutrient); Copper bound to rat intestinal metallothioneins (retained_complex)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/479878-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "643b0358984f3caac8a20e3202c14a073d11ff88758c7a9637b6f8523195658b"}
experimental_model
Dietary radiotracer experiments in rats
exposure
High dietary zinc or copper and reciprocal 64Cu/65Zn absorption measurements.
limitations
High animal dietary concentrations are not human intake thresholds. Copper displacement from metallothionein was the authors’ mechanistic interpretation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
Induced binding proteins provide a mechanism for retaining copper in the gut.
primary_references
[zn-sig-479878] Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat. (1979). https://pubmed.ncbi.nlm.nih.gov/479878/ DOI: 10.1016/s0162-0134(00)80054-9
tissue_or_cell_type
Small intestine
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 915–927
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary radiotracer experiments in rats · source_derived_draft · unverified_draft
### zn-sig-copper-mt-retention The increased intestinal 64Cu was predominantly metallothionein-associated; the authors inferred copper displacement of zinc after zinc-induced metallothionein synthesis. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Induced binding proteins provide a mechanism for retaining copper in the gut. organism: Rattus norvegicus tissue_or_cell_type: Small intestine experimental_model: Dietary radiotracer experiments in rats limitations: High animal dietary concentrations are not human intake thresholds. Copper displacement from metallothionein was the authors’ mechanistic interpretation. exposure: High dietary zinc or copper and reciprocal 64Cu/65Zn absorption measurements. cross_nutrient: Copper (retained_nutrient); Copper bound to rat intestinal metallothioneins (retained_complex) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/479878-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "643b0358984f3caac8a20e3202c14a073d11ff88758c7a9637b6f8523195658b"} [zn-sig-479878] Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat. (1979). https://pubmed.ncbi.nlm.nih.gov/479878/ DOI: 10.1016/s0162-0134(00)80054-9
Complete structured claim and evidence
Raising rat dietary copper from 3 to 24 mg/kg reduced 65Zn absorption by about 20%; further increases to 300 mg/kg did not add inhibition or change zinc association with intestinal metallothionein.
Copper → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc (affected_nutrient); Rat intestinal metallothioneins measured without isoform resolution (unchanged_association)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/479878-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "643b0358984f3caac8a20e3202c14a073d11ff88758c7a9637b6f8523195658b"}
experimental_model
Dietary radiotracer experiments in rats
exposure
High dietary zinc or copper and reciprocal 64Cu/65Zn absorption measurements.
limitations
High animal dietary concentrations are not human intake thresholds. Copper displacement from metallothionein was the authors’ mechanistic interpretation.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
Copper also affected zinc absorption, with a different response pattern.
primary_references
[zn-sig-479878] Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat. (1979). https://pubmed.ncbi.nlm.nih.gov/479878/ DOI: 10.1016/s0162-0134(00)80054-9
tissue_or_cell_type
Small intestine
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 929–941
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary radiotracer experiments in rats · source_derived_draft · unverified_draft
### zn-sig-copper-zinc-absorption Raising rat dietary copper from 3 to 24 mg/kg reduced 65Zn absorption by about 20%; further increases to 300 mg/kg did not add inhibition or change zinc association with intestinal metallothionein. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper also affected zinc absorption, with a different response pattern. organism: Rattus norvegicus tissue_or_cell_type: Small intestine experimental_model: Dietary radiotracer experiments in rats limitations: High animal dietary concentrations are not human intake thresholds. Copper displacement from metallothionein was the authors’ mechanistic interpretation. exposure: High dietary zinc or copper and reciprocal 64Cu/65Zn absorption measurements. cross_nutrient: Zinc (affected_nutrient); Rat intestinal metallothioneins measured without isoform resolution (unchanged_association) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/479878-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "643b0358984f3caac8a20e3202c14a073d11ff88758c7a9637b6f8523195658b"} [zn-sig-479878] Intestinal metallothionein and the mutual antagonism between copper and zinc in the rat. (1979). https://pubmed.ncbi.nlm.nih.gov/479878/ DOI: 10.1016/s0162-0134(00)80054-9
Complete structured claim and evidence
After the tested dietary conditioning, high zinc increased metallothionein-bound copper without changing intracellular copper concentration or significantly altering measured copper absorption in the perfused intestine.
Zinc → Copper bound to rat intestinal metallothioneins source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Copper (affected_nutrient); Intestinal copper absorption (unchanged_endpoint); Rat intestinal metallothioneins measured without isoform resolution (binding_proteins)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/3968585-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ca588cec5326d23dd5f8c9b409ea66fc415043b95af456399e495b8131c8f6ed"}
experimental_model
Isolated vascularly perfused intestine from diet-conditioned rats
exposure
Dietary copper/zinc variation for one week versus direct luminal-metal variation.
limitations
Ex-vivo perfusion and extreme luminal exposure differ from whole-animal feeding; increased metallothionein-bound copper alone did not prove reduced net absorption.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
More copper on a binding protein did not always mean less copper absorption.
primary_references
[zn-sig-3968585] Copper and zinc absorption in the rat: mechanism of mutual antagonism. (1985). https://pubmed.ncbi.nlm.nih.gov/3968585/ DOI: 10.1093/jn/115.2.159
tissue_or_cell_type
Small-intestinal mucosa and portal effluent
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 943–955
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated vascularly perfused intestine from diet-conditioned rats · source_derived_draft · unverified_draft
### zn-sig-mt-binding-not-absorption After the tested dietary conditioning, high zinc increased metallothionein-bound copper without changing intracellular copper concentration or significantly altering measured copper absorption in the perfused intestine. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: More copper on a binding protein did not always mean less copper absorption. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal mucosa and portal effluent experimental_model: Isolated vascularly perfused intestine from diet-conditioned rats limitations: Ex-vivo perfusion and extreme luminal exposure differ from whole-animal feeding; increased metallothionein-bound copper alone did not prove reduced net absorption. exposure: Dietary copper/zinc variation for one week versus direct luminal-metal variation. cross_nutrient: Copper (affected_nutrient); Intestinal copper absorption (unchanged_endpoint); Rat intestinal metallothioneins measured without isoform resolution (binding_proteins) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/3968585-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ca588cec5326d23dd5f8c9b409ea66fc415043b95af456399e495b8131c8f6ed"} [zn-sig-3968585] Copper and zinc absorption in the rat: mechanism of mutual antagonism. (1985). https://pubmed.ncbi.nlm.nih.gov/3968585/ DOI: 10.1093/jn/115.2.159
Complete structured claim and evidence
High luminal zinc reduced both mucosal cytosolic copper and copper transfer into portal effluent in the perfused-rat-intestine experiments.
Zinc → Intestinal copper absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Copper (affected_nutrient)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/3968585-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ca588cec5326d23dd5f8c9b409ea66fc415043b95af456399e495b8131c8f6ed"}
experimental_model
Isolated vascularly perfused intestine from diet-conditioned rats
exposure
Dietary copper/zinc variation for one week versus direct luminal-metal variation.
limitations
Ex-vivo perfusion and extreme luminal exposure differ from whole-animal feeding; increased metallothionein-bound copper alone did not prove reduced net absorption.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
At high luminal exposure, copper entry or transfer was inhibited.
primary_references
[zn-sig-3968585] Copper and zinc absorption in the rat: mechanism of mutual antagonism. (1985). https://pubmed.ncbi.nlm.nih.gov/3968585/ DOI: 10.1093/jn/115.2.159
tissue_or_cell_type
Small-intestinal mucosa and portal effluent
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 957–969
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated vascularly perfused intestine from diet-conditioned rats · source_derived_draft · unverified_draft
### zn-sig-luminal-zinc-copper High luminal zinc reduced both mucosal cytosolic copper and copper transfer into portal effluent in the perfused-rat-intestine experiments. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: At high luminal exposure, copper entry or transfer was inhibited. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal mucosa and portal effluent experimental_model: Isolated vascularly perfused intestine from diet-conditioned rats limitations: Ex-vivo perfusion and extreme luminal exposure differ from whole-animal feeding; increased metallothionein-bound copper alone did not prove reduced net absorption. exposure: Dietary copper/zinc variation for one week versus direct luminal-metal variation. cross_nutrient: Copper (affected_nutrient) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/3968585-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ca588cec5326d23dd5f8c9b409ea66fc415043b95af456399e495b8131c8f6ed"} [zn-sig-3968585] Copper and zinc absorption in the rat: mechanism of mutual antagonism. (1985). https://pubmed.ncbi.nlm.nih.gov/3968585/ DOI: 10.1093/jn/115.2.159
Complete structured claim and evidence
High luminal copper increased mucosal zinc accumulation while reducing zinc transfer to portal effluent at the highest luminal zinc concentration.
Copper → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc (affected_nutrient)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/3968585-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ca588cec5326d23dd5f8c9b409ea66fc415043b95af456399e495b8131c8f6ed"}
experimental_model
Isolated vascularly perfused intestine from diet-conditioned rats
exposure
Dietary copper/zinc variation for one week versus direct luminal-metal variation.
limitations
Ex-vivo perfusion and extreme luminal exposure differ from whole-animal feeding; increased metallothionein-bound copper alone did not prove reduced net absorption.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Rattus norvegicus
plain_language
Copper altered zinc movement through, as well as into, intestinal cells.
primary_references
[zn-sig-3968585] Copper and zinc absorption in the rat: mechanism of mutual antagonism. (1985). https://pubmed.ncbi.nlm.nih.gov/3968585/ DOI: 10.1093/jn/115.2.159
tissue_or_cell_type
Small-intestinal mucosa and portal effluent
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 971–983
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated vascularly perfused intestine from diet-conditioned rats · source_derived_draft · unverified_draft
### zn-sig-luminal-copper-zinc High luminal copper increased mucosal zinc accumulation while reducing zinc transfer to portal effluent at the highest luminal zinc concentration. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper altered zinc movement through, as well as into, intestinal cells. organism: Rattus norvegicus tissue_or_cell_type: Small-intestinal mucosa and portal effluent experimental_model: Isolated vascularly perfused intestine from diet-conditioned rats limitations: Ex-vivo perfusion and extreme luminal exposure differ from whole-animal feeding; increased metallothionein-bound copper alone did not prove reduced net absorption. exposure: Dietary copper/zinc variation for one week versus direct luminal-metal variation. cross_nutrient: Zinc (affected_nutrient) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/3968585-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ca588cec5326d23dd5f8c9b409ea66fc415043b95af456399e495b8131c8f6ed"} [zn-sig-3968585] Copper and zinc absorption in the rat: mechanism of mutual antagonism. (1985). https://pubmed.ncbi.nlm.nih.gov/3968585/ DOI: 10.1093/jn/115.2.159
Complete structured claim and evidence
The study identified CK2-dependent phosphorylation of ZIP7 as a regulatory step preceding cytosolic zinc release from intracellular stores.
Human protein kinase CK2 complex → Human zinc transporter ZIP7 / SLC39A7 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
ZIP7 phosphorylation (regulatory_event); Zinc(II) ion (transported_ion)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/22317921-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "a8e31db38c22019d7ebef8ff165e2b3dc0b3a338e18514f0bf0c48cc5215944d"}
experimental_model
Human breast-cell model with ZIP7/CK2 perturbations
exposure
Signaling stimuli and ZIP7/CK2 phosphorylation comparisons.
limitations
Cellular signaling study; it does not establish dietary zinc supplementation as an anticancer intervention. Intracellular release is different from net dietary uptake.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A kinase can open the route from stored zinc to a cytoplasmic signal.
primary_references
[zn-sig-22317921] Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. (2012). https://pubmed.ncbi.nlm.nih.gov/22317921/ DOI: 10.1126/scisignal.2002585
tissue_or_cell_type
Endoplasmic reticulum and cytoplasm
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 985–997
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human breast-cell model with ZIP7/CK2 perturbations · source_derived_draft · unverified_draft
### zn-sig-ck2-zip7 The study identified CK2-dependent phosphorylation of ZIP7 as a regulatory step preceding cytosolic zinc release from intracellular stores. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kinase can open the route from stored zinc to a cytoplasmic signal. organism: Homo sapiens tissue_or_cell_type: Endoplasmic reticulum and cytoplasm experimental_model: Human breast-cell model with ZIP7/CK2 perturbations limitations: Cellular signaling study; it does not establish dietary zinc supplementation as an anticancer intervention. Intracellular release is different from net dietary uptake. exposure: Signaling stimuli and ZIP7/CK2 phosphorylation comparisons. cross_nutrient: ZIP7 phosphorylation (regulatory_event); Zinc(II) ion (transported_ion) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/22317921-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "a8e31db38c22019d7ebef8ff165e2b3dc0b3a338e18514f0bf0c48cc5215944d"} [zn-sig-22317921] Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. (2012). https://pubmed.ncbi.nlm.nih.gov/22317921/ DOI: 10.1126/scisignal.2002585
Complete structured claim and evidence
ZIP7 phosphorylation was linked to release of stored zinc and downstream AKT and ERK1/2 phosphorylation in the studied human cells.
Human zinc transporter ZIP7 / SLC39A7 → Endoplasmic-reticulum zinc release source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human protein kinase CK2 complex (upstream_kinase); AKT serine/threonine kinase family (downstream_kinase_family); Human ERK2 / MAPK1 (downstream_kinase); Human ERK1 / MAPK3 (downstream_kinase); Cytosolic labile zinc availability (increased_pool)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/22317921-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "a8e31db38c22019d7ebef8ff165e2b3dc0b3a338e18514f0bf0c48cc5215944d"}
experimental_model
Human breast-cell model with ZIP7/CK2 perturbations
exposure
Signaling stimuli and ZIP7/CK2 phosphorylation comparisons.
limitations
Cellular signaling study; it does not establish dietary zinc supplementation as an anticancer intervention. Intracellular release is different from net dietary uptake.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc redistribution connected a storage compartment to kinase signaling.
primary_references
[zn-sig-22317921] Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. (2012). https://pubmed.ncbi.nlm.nih.gov/22317921/ DOI: 10.1126/scisignal.2002585
tissue_or_cell_type
Endoplasmic reticulum and cytoplasm
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 999–1011
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human breast-cell model with ZIP7/CK2 perturbations · source_derived_draft · unverified_draft
### zn-sig-zip7-release ZIP7 phosphorylation was linked to release of stored zinc and downstream AKT and ERK1/2 phosphorylation in the studied human cells. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc redistribution connected a storage compartment to kinase signaling. organism: Homo sapiens tissue_or_cell_type: Endoplasmic reticulum and cytoplasm experimental_model: Human breast-cell model with ZIP7/CK2 perturbations limitations: Cellular signaling study; it does not establish dietary zinc supplementation as an anticancer intervention. Intracellular release is different from net dietary uptake. exposure: Signaling stimuli and ZIP7/CK2 phosphorylation comparisons. cross_nutrient: Human protein kinase CK2 complex (upstream_kinase); AKT serine/threonine kinase family (downstream_kinase_family); Human ERK2 / MAPK1 (downstream_kinase); Human ERK1 / MAPK3 (downstream_kinase); Cytosolic labile zinc availability (increased_pool) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/22317921-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "a8e31db38c22019d7ebef8ff165e2b3dc0b3a338e18514f0bf0c48cc5215944d"} [zn-sig-22317921] Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. (2012). https://pubmed.ncbi.nlm.nih.gov/22317921/ DOI: 10.1126/scisignal.2002585
Complete structured claim and evidence
T-cell receptor activation raised cytoplasmic zinc within one minute, especially near the receptor-contact region; the rise depended on extracellular zinc and was attenuated by ZIP6 suppression.
Human zinc transporter ZIP6 / SLC39A6 → Cytosolic labile zinc availability source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (transported_ion)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/21422171-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "e3b0e519eb5c44185655c0195cb81c713f2b005d70a982466e3e041e997fae59"}
experimental_model
Primary human T-cell receptor signaling study
exposure
Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons.
limitations
Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
ZIP6 helped generate a rapid local zinc signal after receptor activation.
primary_references
[zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
tissue_or_cell_type
CD4 T cells at the receptor-contact region
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1013–1025
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human T-cell receptor signaling study · source_derived_draft · unverified_draft
### zn-sig-zip6-influx T-cell receptor activation raised cytoplasmic zinc within one minute, especially near the receptor-contact region; the rise depended on extracellular zinc and was attenuated by ZIP6 suppression. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: ZIP6 helped generate a rapid local zinc signal after receptor activation. organism: Homo sapiens tissue_or_cell_type: CD4 T cells at the receptor-contact region experimental_model: Primary human T-cell receptor signaling study limitations: Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism. exposure: Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons. cross_nutrient: Zinc(II) ion (transported_ion) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/21422171-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "e3b0e519eb5c44185655c0195cb81c713f2b005d70a982466e3e041e997fae59"} [zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
Complete structured claim and evidence
Increased zinc influx reduced recruitment of SHP-1 to the T-cell receptor activation complex.
Zinc(II) ion → SHP-1 recruitment to the T-cell receptor complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human SHP-1 / PTPN6 (affected_protein); Human zinc transporter ZIP6 / SLC39A6 (upstream_transporter)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/21422171-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "e3b0e519eb5c44185655c0195cb81c713f2b005d70a982466e3e041e997fae59"}
experimental_model
Primary human T-cell receptor signaling study
exposure
Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons.
limitations
Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The zinc signal reduced recruitment of an inhibitory phosphatase.
primary_references
[zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
tissue_or_cell_type
CD4 T cells at the receptor-contact region
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1027–1039
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human T-cell receptor signaling study · source_derived_draft · unverified_draft
### zn-sig-zinc-shp1 Increased zinc influx reduced recruitment of SHP-1 to the T-cell receptor activation complex. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The zinc signal reduced recruitment of an inhibitory phosphatase. organism: Homo sapiens tissue_or_cell_type: CD4 T cells at the receptor-contact region experimental_model: Primary human T-cell receptor signaling study limitations: Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism. exposure: Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons. cross_nutrient: Human SHP-1 / PTPN6 (affected_protein); Human zinc transporter ZIP6 / SLC39A6 (upstream_transporter) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/21422171-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "e3b0e519eb5c44185655c0195cb81c713f2b005d70a982466e3e041e997fae59"} [zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
Complete structured claim and evidence
Greater activation-associated zinc influx augmented ZAP70 phosphorylation in the human T-cell study.
Zinc(II) ion → ZAP70 phosphorylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human ZAP70 (affected_kinase); Human zinc transporter ZIP6 / SLC39A6 (upstream_transporter)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/21422171-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "e3b0e519eb5c44185655c0195cb81c713f2b005d70a982466e3e041e997fae59"}
experimental_model
Primary human T-cell receptor signaling study
exposure
Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons.
limitations
Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A local zinc signal strengthened this receptor-associated kinase response.
primary_references
[zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
tissue_or_cell_type
CD4 T cells at the receptor-contact region
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1041–1053
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human T-cell receptor signaling study · source_derived_draft · unverified_draft
### zn-sig-zinc-zap70 Greater activation-associated zinc influx augmented ZAP70 phosphorylation in the human T-cell study. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A local zinc signal strengthened this receptor-associated kinase response. organism: Homo sapiens tissue_or_cell_type: CD4 T cells at the receptor-contact region experimental_model: Primary human T-cell receptor signaling study limitations: Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism. exposure: Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons. cross_nutrient: Human ZAP70 (affected_kinase); Human zinc transporter ZIP6 / SLC39A6 (upstream_transporter) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/21422171-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "e3b0e519eb5c44185655c0195cb81c713f2b005d70a982466e3e041e997fae59"} [zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
Complete structured claim and evidence
Higher extracellular zinc sustained the cytoplasmic calcium signal after T-cell activation; initial calcium rises were similar, then the signals diverged.
Zinc(II) ion → T-cell cytoplasmic calcium signal source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
calcium ion (signaling_ion); Human zinc transporter ZIP6 / SLC39A6 (upstream_transporter)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/21422171.txt", "locator": "Results: zinc availability and TCR signaling; Figure 4e calcium time course", "file_sha256": "4d36b4fdeeff83b602b0532796814981ee45409241fe40fcd8f7bc1da8beff19"}
experimental_model
Primary human T-cell receptor signaling study
exposure
Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons.
limitations
Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc availability affected how long the calcium signal lasted.
primary_references
[zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
tissue_or_cell_type
CD4 T cells at the receptor-contact region
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1055–1067
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human T-cell receptor signaling study · source_derived_draft · unverified_draft
### zn-sig-zinc-calcium-signal Higher extracellular zinc sustained the cytoplasmic calcium signal after T-cell activation; initial calcium rises were similar, then the signals diverged. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc availability affected how long the calcium signal lasted. organism: Homo sapiens tissue_or_cell_type: CD4 T cells at the receptor-contact region experimental_model: Primary human T-cell receptor signaling study limitations: Culture zinc availability and local signals cannot be mapped directly to oral doses or plasma thresholds. Calcium fluorescence tracks the signal rather than proving one specific calcium channel mechanism. exposure: Receptor activation, extracellular zinc availability and ZIP6 suppression comparisons. cross_nutrient: calcium ion (signaling_ion); Human zinc transporter ZIP6 / SLC39A6 (upstream_transporter) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/21422171.txt", "locator": "Results: zinc availability and TCR signaling; Figure 4e calcium time course", "file_sha256": "4d36b4fdeeff83b602b0532796814981ee45409241fe40fcd8f7bc1da8beff19"} [zn-sig-21422171] Regulation of T cell receptor signaling by activation-induced zinc influx. (2011). https://pubmed.ncbi.nlm.nih.gov/21422171/ DOI: 10.1084/jem.20100031
Complete structured claim and evidence
Zinc supplementation or increased Zip6 expression inhibited LPS-associated upregulation of MHC-II and costimulatory molecules in the dendritic-cell study.
Mouse ZIP6 / Slc39a6 → Dendritic-cell MHC-II and costimulatory markers source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (availability_modifier)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/16892068-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "922aedddf1d5d49fc62e39285307917b93201e23b5b7ea57a60136edd6762a17"}
experimental_model
Dendritic-cell signaling study
exposure
LPS stimulation, zinc supplementation and Zip6 overexpression; exact doses and duration are not verified from the abstract.
limitations
Cell-specific maturation markers are not a general measure of whole-person immune strength. Abstract supports endpoints without unverified protocol details.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
A lower zinc pool accompanied one dendritic-cell maturation response, illustrating cell-specific regulation.
primary_references
[zn-sig-16892068] Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. (2006). https://pubmed.ncbi.nlm.nih.gov/16892068/ DOI: 10.1038/ni1373
tissue_or_cell_type
Dendritic cells
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1069–1081
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dendritic-cell signaling study · source_derived_draft · unverified_draft
### zn-sig-dendritic-maturation Zinc supplementation or increased Zip6 expression inhibited LPS-associated upregulation of MHC-II and costimulatory molecules in the dendritic-cell study. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower zinc pool accompanied one dendritic-cell maturation response, illustrating cell-specific regulation. organism: Mus musculus tissue_or_cell_type: Dendritic cells experimental_model: Dendritic-cell signaling study limitations: Cell-specific maturation markers are not a general measure of whole-person immune strength. Abstract supports endpoints without unverified protocol details. exposure: LPS stimulation, zinc supplementation and Zip6 overexpression; exact doses and duration are not verified from the abstract. cross_nutrient: Zinc(II) ion (availability_modifier) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/16892068-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "922aedddf1d5d49fc62e39285307917b93201e23b5b7ea57a60136edd6762a17"} [zn-sig-16892068] Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. (2006). https://pubmed.ncbi.nlm.nih.gov/16892068/ DOI: 10.1038/ni1373
Complete structured claim and evidence
ZIP10 loss in mature mouse B cells reduced CD45R phosphatase activity.
Mouse mature-B-cell ZIP10 loss → B-cell CD45R phosphatase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse ZIP10 / Slc39a10 (affected_transporter); Mouse CD45R / Ptprc B-cell isoform (affected_phosphatase)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/25074919-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "d3032e44cfa64a54cd560b24872d88e69db456a150510b6e4cde64a11e18b4b7"}
experimental_model
Mature-B-cell Zip10-deficient mice
exposure
B-cell ZIP10 loss versus controls and receptor-activation comparisons.
limitations
Genetic loss is distinct from dietary shortage; CD45R/LYN is the study-supported pathway, not a universal direct zinc activation rule for phosphatases.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
A zinc transporter supported the phosphatase that helps tune B-cell signaling.
primary_references
[zn-sig-25074919] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. (2014). https://pubmed.ncbi.nlm.nih.gov/25074919/ DOI: 10.1073/pnas.1323557111
tissue_or_cell_type
B cells and antibody responses
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1083–1095
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mature-B-cell Zip10-deficient mice · source_derived_draft · unverified_draft
### zn-sig-zip10-cd45r ZIP10 loss in mature mouse B cells reduced CD45R phosphatase activity. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A zinc transporter supported the phosphatase that helps tune B-cell signaling. organism: Mus musculus tissue_or_cell_type: B cells and antibody responses experimental_model: Mature-B-cell Zip10-deficient mice limitations: Genetic loss is distinct from dietary shortage; CD45R/LYN is the study-supported pathway, not a universal direct zinc activation rule for phosphatases. exposure: B-cell ZIP10 loss versus controls and receptor-activation comparisons. cross_nutrient: Mouse ZIP10 / Slc39a10 (affected_transporter); Mouse CD45R / Ptprc B-cell isoform (affected_phosphatase) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/25074919-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "d3032e44cfa64a54cd560b24872d88e69db456a150510b6e4cde64a11e18b4b7"} [zn-sig-25074919] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. (2014). https://pubmed.ncbi.nlm.nih.gov/25074919/ DOI: 10.1073/pnas.1323557111
Complete structured claim and evidence
Reduced CD45R activity in ZIP10-deficient B cells was linked to LYN hyperactivation and dysregulated receptor signaling.
Mouse mature-B-cell ZIP10 loss → B-cell LYN activation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse ZIP10 / Slc39a10 (affected_transporter); Mouse CD45R / Ptprc B-cell isoform (upstream_phosphatase); Mouse LYN kinase (affected_kinase)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/25074919-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "d3032e44cfa64a54cd560b24872d88e69db456a150510b6e4cde64a11e18b4b7"}
experimental_model
Mature-B-cell Zip10-deficient mice
exposure
B-cell ZIP10 loss versus controls and receptor-activation comparisons.
limitations
Genetic loss is distinct from dietary shortage; CD45R/LYN is the study-supported pathway, not a universal direct zinc activation rule for phosphatases.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Losing the transporter caused excessive activity at one signaling step rather than simply turning everything down.
primary_references
[zn-sig-25074919] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. (2014). https://pubmed.ncbi.nlm.nih.gov/25074919/ DOI: 10.1073/pnas.1323557111
tissue_or_cell_type
B cells and antibody responses
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1097–1109
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mature-B-cell Zip10-deficient mice · source_derived_draft · unverified_draft
### zn-sig-zip10-lyn Reduced CD45R activity in ZIP10-deficient B cells was linked to LYN hyperactivation and dysregulated receptor signaling. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing the transporter caused excessive activity at one signaling step rather than simply turning everything down. organism: Mus musculus tissue_or_cell_type: B cells and antibody responses experimental_model: Mature-B-cell Zip10-deficient mice limitations: Genetic loss is distinct from dietary shortage; CD45R/LYN is the study-supported pathway, not a universal direct zinc activation rule for phosphatases. exposure: B-cell ZIP10 loss versus controls and receptor-activation comparisons. cross_nutrient: Mouse ZIP10 / Slc39a10 (affected_transporter); Mouse CD45R / Ptprc B-cell isoform (upstream_phosphatase); Mouse LYN kinase (affected_kinase) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/25074919-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "d3032e44cfa64a54cd560b24872d88e69db456a150510b6e4cde64a11e18b4b7"} [zn-sig-25074919] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. (2014). https://pubmed.ncbi.nlm.nih.gov/25074919/ DOI: 10.1073/pnas.1323557111
Complete structured claim and evidence
Mature-B-cell ZIP10 loss attenuated both T-cell-dependent and T-cell-independent antibody responses; receptor-triggered B-cell proliferation was poor.
Mouse mature-B-cell ZIP10 loss → B-cell antibody response source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse ZIP10 / Slc39a10 (affected_transporter)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/25074919-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "d3032e44cfa64a54cd560b24872d88e69db456a150510b6e4cde64a11e18b4b7"}
experimental_model
Mature-B-cell Zip10-deficient mice
exposure
B-cell ZIP10 loss versus controls and receptor-activation comparisons.
limitations
Genetic loss is distinct from dietary shortage; CD45R/LYN is the study-supported pathway, not a universal direct zinc activation rule for phosphatases.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
The signaling defect impaired the measured antibody responses.
primary_references
[zn-sig-25074919] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. (2014). https://pubmed.ncbi.nlm.nih.gov/25074919/ DOI: 10.1073/pnas.1323557111
tissue_or_cell_type
B cells and antibody responses
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1111–1123
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mature-B-cell Zip10-deficient mice · source_derived_draft · unverified_draft
### zn-sig-zip10-antibody Mature-B-cell ZIP10 loss attenuated both T-cell-dependent and T-cell-independent antibody responses; receptor-triggered B-cell proliferation was poor. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The signaling defect impaired the measured antibody responses. organism: Mus musculus tissue_or_cell_type: B cells and antibody responses experimental_model: Mature-B-cell Zip10-deficient mice limitations: Genetic loss is distinct from dietary shortage; CD45R/LYN is the study-supported pathway, not a universal direct zinc activation rule for phosphatases. exposure: B-cell ZIP10 loss versus controls and receptor-activation comparisons. cross_nutrient: Mouse ZIP10 / Slc39a10 (affected_transporter) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/25074919-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "d3032e44cfa64a54cd560b24872d88e69db456a150510b6e4cde64a11e18b4b7"} [zn-sig-25074919] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength. (2014). https://pubmed.ncbi.nlm.nih.gov/25074919/ DOI: 10.1073/pnas.1323557111
Complete structured claim and evidence
Intestinal epithelial Zip7 deletion increased ER-stress responses in proliferative progenitor cells and was followed by substantial progenitor-cell death.
Mouse intestinal epithelial ZIP7 loss → Intestinal crypt endoplasmic-reticulum stress source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse ZIP7 / Slc39a7 (affected_transporter); Intestinal progenitor-cell survival (reduced_endpoint)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/27736879-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "4ce8fe391aff141b5145e4122917ca1c1817273ab0dd55c7a936b687d9dacdd6"}
experimental_model
Conditional intestinal Zip7-deficient mice and organoids
exposure
Intestinal epithelial versus Lgr5-cell-specific deletion; zinc supplementation comparison.
limitations
Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Loss of zinc distribution machinery stressed the cells that renew the intestinal lining.
primary_references
[zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349
tissue_or_cell_type
Intestinal crypts, progenitor cells and organoids
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1125–1137
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal Zip7-deficient mice and organoids · source_derived_draft · unverified_draft
### zn-sig-zip7-er-stress Intestinal epithelial Zip7 deletion increased ER-stress responses in proliferative progenitor cells and was followed by substantial progenitor-cell death. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of zinc distribution machinery stressed the cells that renew the intestinal lining. organism: Mus musculus tissue_or_cell_type: Intestinal crypts, progenitor cells and organoids experimental_model: Conditional intestinal Zip7-deficient mice and organoids limitations: Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails. exposure: Intestinal epithelial versus Lgr5-cell-specific deletion; zinc supplementation comparison. cross_nutrient: Mouse ZIP7 / Slc39a7 (affected_transporter); Intestinal progenitor-cell survival (reduced_endpoint) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/27736879-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "4ce8fe391aff141b5145e4122917ca1c1817273ab0dd55c7a936b687d9dacdd6"} [zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349
Complete structured claim and evidence
Adding 1 µM ZnSO4 did not suppress ER-stress gene induction in Zip7-deficient intestinal organoids assessed 48 hours after induction of deletion; the study also observed no rescue in fibroblasts, while restored ZIP7 expression rescued their stress response.
Zinc → Intestinal crypt endoplasmic-reticulum stress source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse ZIP7 / Slc39a7 (affected_transporter)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/27736879.txt", "locator": "Results: Zip7 deletion activates ER stress; Figure 4, Figure 5 and supplemental Figure S8", "file_sha256": "4771f8b4a2b4e332b10bd2a5abef6f538cc38f4c85916b44ddab9f15679ed621"}
experimental_model
Conditional intestinal Zip7-deficient mice and organoids
exposure
Supplemental Figure S8: 1 µM ZnSO4; intestinal organoids assessed 48 hours after the study-induced Zip7 deletion. The fibroblast comparison also used 1 µM ZnSO4. This exposure did not suppress the measured ER-stress gene induction.
limitations
Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
More available zinc did not substitute for the missing distribution machinery.
primary_references
[zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349
tissue_or_cell_type
Intestinal crypts, progenitor cells and organoids
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1139–1151
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal Zip7-deficient mice and organoids · source_derived_draft · unverified_draft
### zn-sig-zip7-zinc-no-rescue Adding 1 µM ZnSO4 did not suppress ER-stress gene induction in Zip7-deficient intestinal organoids assessed 48 hours after induction of deletion; the study also observed no rescue in fibroblasts, while restored ZIP7 expression rescued their stress response. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: More available zinc did not substitute for the missing distribution machinery. organism: Mus musculus tissue_or_cell_type: Intestinal crypts, progenitor cells and organoids experimental_model: Conditional intestinal Zip7-deficient mice and organoids limitations: Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails. exposure: Supplemental Figure S8: 1 µM ZnSO4; intestinal organoids assessed 48 hours after the study-induced Zip7 deletion. The fibroblast comparison also used 1 µM ZnSO4. This exposure did not suppress the measured ER-stress gene induction. cross_nutrient: Mouse ZIP7 / Slc39a7 (affected_transporter) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/27736879.txt", "locator": "Results: Zip7 deletion activates ER stress; Figure 4, Figure 5 and supplemental Figure S8", "file_sha256": "4771f8b4a2b4e332b10bd2a5abef6f538cc38f4c85916b44ddab9f15679ed621"} [zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349
Complete structured claim and evidence
Restricting Zip7 deletion to Lgr5-positive stem cells did not impair baseline epithelial homeostasis or crypt-derived organoid formation, unlike deletion across intestinal epithelial cells.
Mouse Lgr5-positive stem-cell ZIP7 loss → Intestinal epithelial renewal source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse ZIP7 / Slc39a7 (affected_transporter)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/27736879.txt", "locator": "Results: Lgr5-positive cell-intrinsic ZIP7; supplemental Figure S4", "file_sha256": "4771f8b4a2b4e332b10bd2a5abef6f538cc38f4c85916b44ddab9f15679ed621"}
experimental_model
Conditional intestinal Zip7-deficient mice and organoids
exposure
Intestinal epithelial versus Lgr5-cell-specific deletion; zinc supplementation comparison.
limitations
Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
The affected cell population changed the outcome of the same transporter loss.
primary_references
[zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349
tissue_or_cell_type
Intestinal crypts, progenitor cells and organoids
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1153–1165
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal Zip7-deficient mice and organoids · source_derived_draft · unverified_draft
### zn-sig-zip7-lineage-null Restricting Zip7 deletion to Lgr5-positive stem cells did not impair baseline epithelial homeostasis or crypt-derived organoid formation, unlike deletion across intestinal epithelial cells. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The affected cell population changed the outcome of the same transporter loss. organism: Mus musculus tissue_or_cell_type: Intestinal crypts, progenitor cells and organoids experimental_model: Conditional intestinal Zip7-deficient mice and organoids limitations: Cell lineage and tissue context matter. Supplementation failing to rescue a transporter defect is not evidence that ordinary dietary zinc replacement fails. exposure: Intestinal epithelial versus Lgr5-cell-specific deletion; zinc supplementation comparison. cross_nutrient: Mouse ZIP7 / Slc39a7 (affected_transporter) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/27736879.txt", "locator": "Results: Lgr5-positive cell-intrinsic ZIP7; supplemental Figure S4", "file_sha256": "4771f8b4a2b4e332b10bd2a5abef6f538cc38f4c85916b44ddab9f15679ed621"} [zn-sig-27736879] Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress. (2016). https://pubmed.ncbi.nlm.nih.gov/27736879/ DOI: 10.1371/journal.pgen.1006349
Complete structured claim and evidence
A zinc chelator mimicked the dendritic-cell effects of LPS in the primary study, which linked reduced intracellular free zinc to the maturation-marker response.
Zinc → Dendritic-cell MHC-II and costimulatory markers source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Zinc(II) ion (availability_modifier)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/16892068-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "922aedddf1d5d49fc62e39285307917b93201e23b5b7ea57a60136edd6762a17"}
experimental_model
Dendritic-cell signaling study
exposure
Experimental zinc chelation, not dietary zinc restriction. Chelator identity, concentration and exposure time are not verified in the indexed abstract.
limitations
Chelation is a manipulation of available cellular zinc. It is not evidence for a human intake threshold or a universal immune benefit of low zinc.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
Experimentally binding available zinc reproduced part of the dendritic-cell response.
primary_references
[zn-sig-16892068] Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. (2006). https://pubmed.ncbi.nlm.nih.gov/16892068/ DOI: 10.1038/ni1373
tissue_or_cell_type
Dendritic cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1167–1179
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dendritic-cell signaling study · source_derived_draft · unverified_draft
### zn-sig-dendritic-chelation A zinc chelator mimicked the dendritic-cell effects of LPS in the primary study, which linked reduced intracellular free zinc to the maturation-marker response. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Experimentally binding available zinc reproduced part of the dendritic-cell response. organism: Mus musculus tissue_or_cell_type: Dendritic cells experimental_model: Dendritic-cell signaling study limitations: Chelation is a manipulation of available cellular zinc. It is not evidence for a human intake threshold or a universal immune benefit of low zinc. exposure: Experimental zinc chelation, not dietary zinc restriction. Chelator identity, concentration and exposure time are not verified in the indexed abstract. cross_nutrient: Zinc(II) ion (availability_modifier) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/16892068-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "922aedddf1d5d49fc62e39285307917b93201e23b5b7ea57a60136edd6762a17"} [zn-sig-16892068] Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. (2006). https://pubmed.ncbi.nlm.nih.gov/16892068/ DOI: 10.1038/ni1373
Complete structured claim and evidence
After ten weeks, erythrocyte Cu/Zn-superoxide dismutase activity was lower than pretreatment in both the zinc-only and zinc-plus-iron groups (P<0.05).
Zinc gluconate → Erythrocyte copper/zinc superoxide dismutase activity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Copper (affected_nutrient); Iron (coadministered_nutrient); Zinc(II) ion (administered_element)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969}
experimental_model
Ten-week zinc or zinc-plus-iron intervention in adult women
exposure
50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate.
limitations
Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Adding iron did not prevent the fall in this copper/zinc enzyme marker.
primary_references
[zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145
tissue_or_cell_type
Blood and erythrocytes
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1181–1194
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-week zinc or zinc-plus-iron intervention in adult women · source_derived_draft · unverified_draft
### zn-clin-esod-zinc After ten weeks, erythrocyte Cu/Zn-superoxide dismutase activity was lower than pretreatment in both the zinc-only and zinc-plus-iron groups (P<0.05). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding iron did not prevent the fall in this copper/zinc enzyme marker. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Ten-week zinc or zinc-plus-iron intervention in adult women limitations: Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency. exposure: 50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate. cross_nutrient: Copper (affected_nutrient); Iron (coadministered_nutrient); Zinc(II) ion (administered_element) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969} [zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145
Complete structured claim and evidence
Zinc-only treatment was followed by lower serum ferritin and hematocrit; with added iron, ferritin increased and hematocrit was unchanged. Hemoglobin did not change in either group.
Zinc gluconate → Serum ferritin concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron (coadministered_nutrient); Hematocrit (measured_endpoint); Blood hemoglobin concentration (unchanged_endpoint)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969}
experimental_model
Ten-week zinc or zinc-plus-iron intervention in adult women
exposure
50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate.
limitations
Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Iron-status markers responded differently depending on whether iron accompanied zinc.
primary_references
[zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145
tissue_or_cell_type
Blood and erythrocytes
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1196–1209
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-week zinc or zinc-plus-iron intervention in adult women · source_derived_draft · unverified_draft
### zn-clin-iron-markers Zinc-only treatment was followed by lower serum ferritin and hematocrit; with added iron, ferritin increased and hematocrit was unchanged. Hemoglobin did not change in either group. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-status markers responded differently depending on whether iron accompanied zinc. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Ten-week zinc or zinc-plus-iron intervention in adult women limitations: Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency. exposure: 50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate. cross_nutrient: Iron (coadministered_nutrient); Hematocrit (measured_endpoint); Blood hemoglobin concentration (unchanged_endpoint) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969} [zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145
Complete structured claim and evidence
Serum ceruloplasmin was unchanged in both intervention groups despite lower erythrocyte Cu/Zn-superoxide dismutase activity; serum zinc rose in both groups.
Zinc gluconate → Serum ceruloplasmin concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Copper (affected_nutrient); Serum zinc concentration (increased_marker); Erythrocyte copper/zinc superoxide dismutase activity (decreased_marker)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969}
experimental_model
Ten-week zinc or zinc-plus-iron intervention in adult women
exposure
50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate.
limitations
Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A rising zinc blood level and unchanged ceruloplasmin did not capture every functional change.
primary_references
[zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145
tissue_or_cell_type
Blood and erythrocytes
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1211–1224
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-week zinc or zinc-plus-iron intervention in adult women · source_derived_draft · unverified_draft
### zn-clin-ceruloplasmin-null Serum ceruloplasmin was unchanged in both intervention groups despite lower erythrocyte Cu/Zn-superoxide dismutase activity; serum zinc rose in both groups. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A rising zinc blood level and unchanged ceruloplasmin did not capture every functional change. organism: Homo sapiens tissue_or_cell_type: Blood and erythrocytes experimental_model: Ten-week zinc or zinc-plus-iron intervention in adult women limitations: Reported comparisons are within-group pretreatment versus 10 weeks, not placebo-adjusted effects. ESOD is a functional biomarker, not a diagnosis of symptomatic copper deficiency. exposure: 50 mg elemental zinc/day as gluconate, with or without 50 mg iron/day as ferrous sulfate monohydrate. cross_nutrient: Copper (affected_nutrient); Serum zinc concentration (increased_marker); Erythrocyte copper/zinc superoxide dismutase activity (decreased_marker) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/yadrick1989.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "utf8_bytes": 969} [zn-clin-yadrick1989] Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. (1989). https://pubmed.ncbi.nlm.nih.gov/2912000/ DOI: 10.1093/ajcn/49.1.145
Complete structured claim and evidence
Fasting-water zinc absorption was 59%, 58% and 34% at ferrous Fe:Zn molar ratios of 1:1, 2.5:1 and 25:1 respectively; inhibition was significant at the highest ratio.
Ferrous iron → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}
experimental_model
Human 65Zn tracer study with whole-body counting after two weeks
exposure
Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.
limitations
Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The high iron-to-zinc ratio reduced zinc uptake in the fasting solution.
primary_references
[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1226–1239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft
### zn-clin-iron-fasting Fasting-water zinc absorption was 59%, 58% and 34% at ferrous Fe:Zn molar ratios of 1:1, 2.5:1 and 25:1 respectively; inhibition was significant at the highest ratio. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The high iron-to-zinc ratio reduced zinc uptake in the fasting solution. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
Complete structured claim and evidence
When the corresponding iron-to-zinc ratios were administered with a meal, zinc absorption was 25%, 23% and 22%, without the inhibitory iron effect detected in fasting water. Two weeks of iron preloading also did not alter zinc absorption from water.
Ferrous iron → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}
experimental_model
Human 65Zn tracer study with whole-body counting after two weeks
exposure
Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.
limitations
Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The fasting-solution result did not carry over to the tested meal.
primary_references
[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1241–1254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft
### zn-clin-iron-meal When the corresponding iron-to-zinc ratios were administered with a meal, zinc absorption was 25%, 23% and 22%, without the inhibitory iron effect detected in fasting water. Two weeks of iron preloading also did not alter zinc absorption from water. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fasting-solution result did not carry over to the tested meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
Complete structured claim and evidence
Adding histidine to the high-iron water solution attenuated inhibition, with zinc absorption of 47% compared with 34% at the high iron ratio without that ligand.
L-Histidine → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Ferrous iron (competing_ion); Zinc(II) ion (absorbed_ion)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}
experimental_model
Human 65Zn tracer study with whole-body counting after two weeks
exposure
Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.
limitations
Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A ligand changed the interaction between iron and zinc in this experiment.
primary_references
[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1256–1269
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft
### zn-clin-histidine-iron Adding histidine to the high-iron water solution attenuated inhibition, with zinc absorption of 47% compared with 34% at the high iron ratio without that ligand. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A ligand changed the interaction between iron and zinc in this experiment. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Ferrous iron (competing_ion); Zinc(II) ion (absorbed_ion) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
Complete structured claim and evidence
Zinc absorption fractions were 32.8±2.3%, 26.9±2.4%, 39.4±2.4% and 26.2±2.3% (mean±SE) for moderate-Ca/low-phytate, moderate-Ca/high-phytate, high-Ca/low-phytate and high-Ca/high-phytate menus. Phytate reduced absorption; calcium did not significantly impair it.
Phytic acid / phytate → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
absolute_absorption
Corresponding absolute absorption: 3.8±0.3, 3.0±0.3, 4.5±0.3 and 3.2±0.3 mg zinc/day (mean±SE).
cross_nutrient
Calcium (dietary_context); Zinc (measured_nutrient)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hunt2009.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "d912d9f2c0890cde2ae13e9de7f1202bf130e661e3f14e13483563f179319f85", "utf8_bytes": 1659}
experimental_model
Two-by-two one-day feeding and 65Zn tracer study in ten healthy women
exposure
Approximately 700 versus 1800 mg calcium/day, and 440 versus 1800 mg phytate/day in conventional menus.
limitations
Short controlled menus in ten women; null calcium effect does not cover every formulation, population or dose.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Phytate reduced zinc uptake in these menus, while extra calcium did not.
primary_references
[zn-clin-hunt2009] Dietary calcium does not exacerbate phytate inhibition of zinc absorption by women from conventional diets. (2009). https://pubmed.ncbi.nlm.nih.gov/19176739/ DOI: 10.3945/ajcn.2008.27175
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1271–1285
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-by-two one-day feeding and 65Zn tracer study in ten healthy women · source_derived_draft · unverified_draft
### zn-clin-phytate-calcium Zinc absorption fractions were 32.8±2.3%, 26.9±2.4%, 39.4±2.4% and 26.2±2.3% (mean±SE) for moderate-Ca/low-phytate, moderate-Ca/high-phytate, high-Ca/low-phytate and high-Ca/high-phytate menus. Phytate reduced absorption; calcium did not significantly impair it. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phytate reduced zinc uptake in these menus, while extra calcium did not. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Two-by-two one-day feeding and 65Zn tracer study in ten healthy women limitations: Short controlled menus in ten women; null calcium effect does not cover every formulation, population or dose. exposure: Approximately 700 versus 1800 mg calcium/day, and 440 versus 1800 mg phytate/day in conventional menus. cross_nutrient: Calcium (dietary_context); Zinc (measured_nutrient) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hunt2009.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "d912d9f2c0890cde2ae13e9de7f1202bf130e661e3f14e13483563f179319f85", "utf8_bytes": 1659} absolute_absorption: Corresponding absolute absorption: 3.8±0.3, 3.0±0.3, 4.5±0.3 and 3.2±0.3 mg zinc/day (mean±SE). [zn-clin-hunt2009] Dietary calcium does not exacerbate phytate inhibition of zinc absorption by women from conventional diets. (2009). https://pubmed.ncbi.nlm.nih.gov/19176739/ DOI: 10.3945/ajcn.2008.27175
Complete structured claim and evidence
At added phytate-P levels of 0, 25, 50, 75, 100, 140, 175 and 250 mg, mean zinc absorption was 22%, 16%, 14%, 11%, 7%, 7%, 7% and 6%. Reductions were significant from 50 mg phytate-P in these meals.
Phytic acid / phytate → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc (absorbed_nutrient); Calcium (meal_context)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603}
experimental_model
Human dual-radioisotope meal study: 40 subjects, 105 meals
exposure
Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus.
limitations
Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Increasing phytate progressively reduced zinc uptake in the test meal.
primary_references
[zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
tissue_or_cell_type
Intestinal zinc absorption and whole-body calcium retention
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1287–1300
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dual-radioisotope meal study: 40 subjects, 105 meals · source_derived_draft · unverified_draft
### zn-clin-phytate-gradient At added phytate-P levels of 0, 25, 50, 75, 100, 140, 175 and 250 mg, mean zinc absorption was 22%, 16%, 14%, 11%, 7%, 7%, 7% and 6%. Reductions were significant from 50 mg phytate-P in these meals. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing phytate progressively reduced zinc uptake in the test meal. organism: Homo sapiens tissue_or_cell_type: Intestinal zinc absorption and whole-body calcium retention experimental_model: Human dual-radioisotope meal study: 40 subjects, 105 meals limitations: Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds. exposure: Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus. cross_nutrient: Zinc (absorbed_nutrient); Calcium (meal_context) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603} [zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
Complete structured claim and evidence
At the same ascending phytate-P additions, seven-day calcium retention was 31%, 28%, 27%, 26%, 22%, 19%, 14% and 11%; reduction was significant from 100 mg phytate-P in this study.
Phytic acid / phytate → Whole-body calcium retention source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium (retained_nutrient); Zinc (concurrently_measured_nutrient)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603}
experimental_model
Human dual-radioisotope meal study: 40 subjects, 105 meals
exposure
Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus.
limitations
Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The same meal manipulation also reduced retained calcium.
primary_references
[zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
tissue_or_cell_type
Intestinal zinc absorption and whole-body calcium retention
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1302–1315
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dual-radioisotope meal study: 40 subjects, 105 meals · source_derived_draft · unverified_draft
### zn-clin-phytate-calcium-retention At the same ascending phytate-P additions, seven-day calcium retention was 31%, 28%, 27%, 26%, 22%, 19%, 14% and 11%; reduction was significant from 100 mg phytate-P in this study. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same meal manipulation also reduced retained calcium. organism: Homo sapiens tissue_or_cell_type: Intestinal zinc absorption and whole-body calcium retention experimental_model: Human dual-radioisotope meal study: 40 subjects, 105 meals limitations: Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds. exposure: Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus. cross_nutrient: Calcium (retained_nutrient); Zinc (concurrently_measured_nutrient) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603} [zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
Complete structured claim and evidence
Absorption efficiency increased as dietary zinc fell. After 4–8 weeks below 11 mg zinc/day, further adaptation reached as high as 92% absorption on low-phytate diets; this additional adaptation was absent on high-phytate diets.
Zinc → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Phytic acid / phytate (dietary_modifier)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hunt2008.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "da28b136fa7271f3406a8cf55cc3e613a5e8749578c1ee662057ebe564df8995", "utf8_bytes": 1647}
experimental_model
Three controlled dietary experiments in 109 healthy adults
exposure
Ten diets: 4–29 mg zinc/day, phytate:zinc molar ratios 2–7 or 15–23, before and after 4 or 8 weeks.
limitations
Dietary restriction and adaptation are not proof of clinical zinc deficiency. The reported 92% was an upper observed absorption value, not a mean.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc uptake can adapt to intake, but phytate constrained that adaptation.
primary_references
[zn-clin-hunt2008] Adaptation in human zinc absorption as influenced by dietary zinc and bioavailability. (2008). https://pubmed.ncbi.nlm.nih.gov/18469257/ DOI: 10.1093/ajcn/87.5.1336
tissue_or_cell_type
Intestinal absorption and candidate blood biomarkers
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1317–1330
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three controlled dietary experiments in 109 healthy adults · source_derived_draft · unverified_draft
### zn-clin-adaptation Absorption efficiency increased as dietary zinc fell. After 4–8 weeks below 11 mg zinc/day, further adaptation reached as high as 92% absorption on low-phytate diets; this additional adaptation was absent on high-phytate diets. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc uptake can adapt to intake, but phytate constrained that adaptation. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption and candidate blood biomarkers experimental_model: Three controlled dietary experiments in 109 healthy adults limitations: Dietary restriction and adaptation are not proof of clinical zinc deficiency. The reported 92% was an upper observed absorption value, not a mean. exposure: Ten diets: 4–29 mg zinc/day, phytate:zinc molar ratios 2–7 or 15–23, before and after 4 or 8 weeks. cross_nutrient: Phytic acid / phytate (dietary_modifier) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hunt2008.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "da28b136fa7271f3406a8cf55cc3e613a5e8749578c1ee662057ebe564df8995", "utf8_bytes": 1647} [zn-clin-hunt2008] Adaptation in human zinc absorption as influenced by dietary zinc and bioavailability. (2008). https://pubmed.ncbi.nlm.nih.gov/18469257/ DOI: 10.1093/ajcn/87.5.1336
Complete structured claim and evidence
Erythrocyte osmotic fragility, in-vitro erythrocyte 65Zn uptake, and leukocyte ZIP1 and ZnT1 expression did not respond to dietary zinc content in these experiments.
Zinc → Candidate biomarkers during dietary zinc adaptation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hunt2008.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "da28b136fa7271f3406a8cf55cc3e613a5e8749578c1ee662057ebe564df8995", "utf8_bytes": 1647}
experimental_model
Three controlled dietary experiments in 109 healthy adults
exposure
Ten diets: 4–29 mg zinc/day, phytate:zinc molar ratios 2–7 or 15–23, before and after 4 or 8 weeks.
limitations
Dietary restriction and adaptation are not proof of clinical zinc deficiency. The reported 92% was an upper observed absorption value, not a mean.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Several candidate blood tests missed the dietary differences.
primary_references
[zn-clin-hunt2008] Adaptation in human zinc absorption as influenced by dietary zinc and bioavailability. (2008). https://pubmed.ncbi.nlm.nih.gov/18469257/ DOI: 10.1093/ajcn/87.5.1336
tissue_or_cell_type
Intestinal absorption and candidate blood biomarkers
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1332–1345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three controlled dietary experiments in 109 healthy adults · source_derived_draft · unverified_draft
### zn-clin-adaptation-markers Erythrocyte osmotic fragility, in-vitro erythrocyte 65Zn uptake, and leukocyte ZIP1 and ZnT1 expression did not respond to dietary zinc content in these experiments. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several candidate blood tests missed the dietary differences. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption and candidate blood biomarkers experimental_model: Three controlled dietary experiments in 109 healthy adults limitations: Dietary restriction and adaptation are not proof of clinical zinc deficiency. The reported 92% was an upper observed absorption value, not a mean. exposure: Ten diets: 4–29 mg zinc/day, phytate:zinc molar ratios 2–7 or 15–23, before and after 4 or 8 weeks. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hunt2008.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "da28b136fa7271f3406a8cf55cc3e613a5e8749578c1ee662057ebe564df8995", "utf8_bytes": 1647} [zn-clin-hunt2008] Adaptation in human zinc absorption as influenced by dietary zinc and bioavailability. (2008). https://pubmed.ncbi.nlm.nih.gov/18469257/ DOI: 10.1093/ajcn/87.5.1336
Complete structured claim and evidence
Experimental human zinc restriction reduced interferon gamma production, contributing to the selective decline in the tested TH1-associated cytokine response.
Zinc → T-cell interferon gamma production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Interferon gamma (measured_cytokine)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106}
experimental_model
Experimental dietary zinc restriction and repletion in humans
exposure
Baseline, end of zinc restriction, and following repletion were assessed.
limitations
Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc shortage reduced interferon gamma production in the tested immune cells.
primary_references
[zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
tissue_or_cell_type
T lymphocytes and cytokine production
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1347–1360
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Experimental dietary zinc restriction and repletion in humans · source_derived_draft · unverified_draft
### zn-clin-depletion-ifng Experimental human zinc restriction reduced interferon gamma production, contributing to the selective decline in the tested TH1-associated cytokine response. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc shortage reduced interferon gamma production in the tested immune cells. organism: Homo sapiens tissue_or_cell_type: T lymphocytes and cytokine production experimental_model: Experimental dietary zinc restriction and repletion in humans limitations: Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk. exposure: Baseline, end of zinc restriction, and following repletion were assessed. cross_nutrient: Interferon gamma (measured_cytokine) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106} [zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
Complete structured claim and evidence
Experimental human zinc restriction reduced interleukin-2 production, contributing to the selective decline in the tested TH1-associated cytokine response.
Zinc → T-cell interleukin-2 production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
interleukin-2 (measured_cytokine)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106}
experimental_model
Experimental dietary zinc restriction and repletion in humans
exposure
Baseline, end of zinc restriction, and following repletion were assessed.
limitations
Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc shortage reduced interleukin-2 production in the tested immune cells.
primary_references
[zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
tissue_or_cell_type
T lymphocytes and cytokine production
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1362–1375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Experimental dietary zinc restriction and repletion in humans · source_derived_draft · unverified_draft
### zn-clin-depletion-il2 Experimental human zinc restriction reduced interleukin-2 production, contributing to the selective decline in the tested TH1-associated cytokine response. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc shortage reduced interleukin-2 production in the tested immune cells. organism: Homo sapiens tissue_or_cell_type: T lymphocytes and cytokine production experimental_model: Experimental dietary zinc restriction and repletion in humans limitations: Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk. exposure: Baseline, end of zinc restriction, and following repletion were assessed. cross_nutrient: interleukin-2 (measured_cytokine) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106} [zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
Complete structured claim and evidence
Experimental human zinc restriction reduced tumor necrosis factor alpha production, contributing to the selective decline in the tested TH1-associated cytokine response.
Zinc → T-cell tumor necrosis factor production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Tumor necrosis factor (measured_cytokine)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106}
experimental_model
Experimental dietary zinc restriction and repletion in humans
exposure
Baseline, end of zinc restriction, and following repletion were assessed.
limitations
Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc shortage reduced tumor necrosis factor alpha production in the tested immune cells.
primary_references
[zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
tissue_or_cell_type
T lymphocytes and cytokine production
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1377–1390
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Experimental dietary zinc restriction and repletion in humans · source_derived_draft · unverified_draft
### zn-clin-depletion-tnf Experimental human zinc restriction reduced tumor necrosis factor alpha production, contributing to the selective decline in the tested TH1-associated cytokine response. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc shortage reduced tumor necrosis factor alpha production in the tested immune cells. organism: Homo sapiens tissue_or_cell_type: T lymphocytes and cytokine production experimental_model: Experimental dietary zinc restriction and repletion in humans limitations: Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk. exposure: Baseline, end of zinc restriction, and following repletion were assessed. cross_nutrient: Tumor necrosis factor (measured_cytokine) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106} [zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
Complete structured claim and evidence
Production of IL4, IL6 and IL10 was unchanged during the reported zinc-deficiency experiment, unlike the TH1-associated cytokines.
Zinc → T-cell IL4, IL6 and IL10 production profile source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Interleukin 4 (measured_cytokine); interleukin 6 (measured_cytokine); Interleukin 10 (measured_cytokine)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106}
experimental_model
Experimental dietary zinc restriction and repletion in humans
exposure
Baseline, end of zinc restriction, and following repletion were assessed.
limitations
Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Zinc shortage did not suppress every cytokine in the same way.
primary_references
[zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
tissue_or_cell_type
T lymphocytes and cytokine production
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1392–1405
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Experimental dietary zinc restriction and repletion in humans · source_derived_draft · unverified_draft
### zn-clin-depletion-th2-null Production of IL4, IL6 and IL10 was unchanged during the reported zinc-deficiency experiment, unlike the TH1-associated cytokines. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc shortage did not suppress every cytokine in the same way. organism: Homo sapiens tissue_or_cell_type: T lymphocytes and cytokine production experimental_model: Experimental dietary zinc restriction and repletion in humans limitations: Indexed abstract only; no sample size, intake, duration, assay stimulus or repletion effect size is invented. Changes in selected cytokines do not quantify overall infection risk. exposure: Baseline, end of zinc restriction, and following repletion were assessed. cross_nutrient: Interleukin 4 (measured_cytokine); interleukin 6 (measured_cytokine); Interleukin 10 (measured_cytokine) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/beck1997.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "f731be20460b3ded18a253c1d1595c48849db9c09ef164f8a7d03a552e5619dd", "utf8_bytes": 1106} [zn-clin-beck1997] Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. (1997). https://pubmed.ncbi.nlm.nih.gov/9227444/ DOI: 10.1152/ajpendo.1997.272.6.e1002
Complete structured claim and evidence
An adult with sickle cell anemia developed hypocupremia after two years of zinc therapy, accompanied by microcytosis and relative neutropenia. Additional zinc-treated patients had varying hypoceruloplasminemia.
Zinc → Plasma copper concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Copper (deficient_nutrient); Erythrocyte mean cell volume (reduced_endpoint); Blood neutrophil count (reduced_endpoint); Serum ceruloplasmin concentration (associated_marker)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/prasad1978.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "7c4b85a9dd24c3e3bfd04414c0add5d0fa2bcc8c15b5e46bded351e2a2f01e3f", "utf8_bytes": 487}
experimental_model
Clinical case and additional observations in adults with sickle cell anemia receiving zinc therapy
exposure
Index patient received zinc as an antisickling intervention for two years; copper was subsequently administered.
limitations
Case evidence in a particular disease setting; dose and formulation are not verified from the abstract. Does not establish incidence or a universal zinc:copper supplement ratio.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Long zinc treatment was associated with copper shortage and blood-cell changes.
primary_references
[zn-clin-prasad1978] Hypocupremia induced by zinc therapy in adults. (1978). https://pubmed.ncbi.nlm.nih.gov/359844/ DOI: 10.1001/jama.1978.03290200044019
tissue_or_cell_type
Blood copper and hematology
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1407–1420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical case and additional observations in adults with sickle cell anemia receiving zinc therapy · source_derived_draft · unverified_draft
### zn-clin-hypocupremia An adult with sickle cell anemia developed hypocupremia after two years of zinc therapy, accompanied by microcytosis and relative neutropenia. Additional zinc-treated patients had varying hypoceruloplasminemia. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Long zinc treatment was associated with copper shortage and blood-cell changes. organism: Homo sapiens tissue_or_cell_type: Blood copper and hematology experimental_model: Clinical case and additional observations in adults with sickle cell anemia receiving zinc therapy limitations: Case evidence in a particular disease setting; dose and formulation are not verified from the abstract. Does not establish incidence or a universal zinc:copper supplement ratio. exposure: Index patient received zinc as an antisickling intervention for two years; copper was subsequently administered. cross_nutrient: Copper (deficient_nutrient); Erythrocyte mean cell volume (reduced_endpoint); Blood neutrophil count (reduced_endpoint); Serum ceruloplasmin concentration (associated_marker) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/prasad1978.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "7c4b85a9dd24c3e3bfd04414c0add5d0fa2bcc8c15b5e46bded351e2a2f01e3f", "utf8_bytes": 487} [zn-clin-prasad1978] Hypocupremia induced by zinc therapy in adults. (1978). https://pubmed.ncbi.nlm.nih.gov/359844/ DOI: 10.1001/jama.1978.03290200044019
Complete structured claim and evidence
Copper administration increased erythrocyte size and leukocyte counts in the reported index patient; the authors also reported correction of hypoceruloplasminemia in additional zinc-treated patients.
Copper → Erythrocyte mean cell volume source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Zinc (prior_exposure); Blood leukocyte count (increased_endpoint); Serum ceruloplasmin concentration (responsive_marker)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/prasad1978.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "7c4b85a9dd24c3e3bfd04414c0add5d0fa2bcc8c15b5e46bded351e2a2f01e3f", "utf8_bytes": 487}
experimental_model
Clinical case and additional observations in adults with sickle cell anemia receiving zinc therapy
exposure
Index patient received zinc as an antisickling intervention for two years; copper was subsequently administered.
limitations
Case evidence in a particular disease setting; dose and formulation are not verified from the abstract. Does not establish incidence or a universal zinc:copper supplement ratio.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Copper replacement improved the reported blood-cell abnormalities.
primary_references
[zn-clin-prasad1978] Hypocupremia induced by zinc therapy in adults. (1978). https://pubmed.ncbi.nlm.nih.gov/359844/ DOI: 10.1001/jama.1978.03290200044019
tissue_or_cell_type
Blood copper and hematology
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1422–1435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical case and additional observations in adults with sickle cell anemia receiving zinc therapy · source_derived_draft · unverified_draft
### zn-clin-copper-response Copper administration increased erythrocyte size and leukocyte counts in the reported index patient; the authors also reported correction of hypoceruloplasminemia in additional zinc-treated patients. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper replacement improved the reported blood-cell abnormalities. organism: Homo sapiens tissue_or_cell_type: Blood copper and hematology experimental_model: Clinical case and additional observations in adults with sickle cell anemia receiving zinc therapy limitations: Case evidence in a particular disease setting; dose and formulation are not verified from the abstract. Does not establish incidence or a universal zinc:copper supplement ratio. exposure: Index patient received zinc as an antisickling intervention for two years; copper was subsequently administered. cross_nutrient: Zinc (prior_exposure); Blood leukocyte count (increased_endpoint); Serum ceruloplasmin concentration (responsive_marker) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/prasad1978.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "7c4b85a9dd24c3e3bfd04414c0add5d0fa2bcc8c15b5e46bded351e2a2f01e3f", "utf8_bytes": 487} [zn-clin-prasad1978] Hypocupremia induced by zinc therapy in adults. (1978). https://pubmed.ncbi.nlm.nih.gov/359844/ DOI: 10.1001/jama.1978.03290200044019
Complete structured claim and evidence
Fasting/post-meal plasma zinc means were 71/60 µg per 100 mL in cirrhosis, 76/64 in malabsorption and 97/81 in controls; the study also documented diurnal variation.
Zinc → Plasma zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/walker1973.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "350425d75c9023c5b9ddb97d734e320b4e07c6fe5b834213defb1adc7cc26b00", "utf8_bytes": 991}
experimental_model
Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients
exposure
Fasting and post-meal plasma samples; disease-group comparisons.
limitations
Correlations cannot distinguish dietary shortage from albumin binding, redistribution and disease effects. Plasma measurements are not intracellular zinc thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Blood sampling time and disease context changed the measured zinc level.
primary_references
[zn-clin-walker1973] Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis. (1973). https://pubmed.ncbi.nlm.nih.gov/4785284/ DOI: 10.1136/gut.14.12.943
tissue_or_cell_type
Plasma and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1437–1450
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients · source_derived_draft · unverified_draft
### zn-clin-plasma-meals Fasting/post-meal plasma zinc means were 71/60 µg per 100 mL in cirrhosis, 76/64 in malabsorption and 97/81 in controls; the study also documented diurnal variation. Condition category: biomarker_context nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood sampling time and disease context changed the measured zinc level. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients limitations: Correlations cannot distinguish dietary shortage from albumin binding, redistribution and disease effects. Plasma measurements are not intracellular zinc thresholds. exposure: Fasting and post-meal plasma samples; disease-group comparisons. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/walker1973.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "350425d75c9023c5b9ddb97d734e320b4e07c6fe5b834213defb1adc7cc26b00", "utf8_bytes": 991} [zn-clin-walker1973] Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis. (1973). https://pubmed.ncbi.nlm.nih.gov/4785284/ DOI: 10.1136/gut.14.12.943
Complete structured claim and evidence
Plasma zinc correlated with plasma albumin in the cirrhosis and malabsorption groups, supporting albumin as one contributor to lower measured circulating zinc.
Plasma albumin concentration → Plasma zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Human serum albumin (carrier_protein)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/walker1973.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "350425d75c9023c5b9ddb97d734e320b4e07c6fe5b834213defb1adc7cc26b00", "utf8_bytes": 991}
experimental_model
Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients
exposure
Fasting and post-meal plasma samples; disease-group comparisons.
limitations
Correlations cannot distinguish dietary shortage from albumin binding, redistribution and disease effects. Plasma measurements are not intracellular zinc thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A lower carrier-protein level can help explain a lower plasma zinc reading.
primary_references
[zn-clin-walker1973] Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis. (1973). https://pubmed.ncbi.nlm.nih.gov/4785284/ DOI: 10.1136/gut.14.12.943
tissue_or_cell_type
Plasma and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1452–1465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients · source_derived_draft · unverified_draft
### zn-clin-plasma-albumin Plasma zinc correlated with plasma albumin in the cirrhosis and malabsorption groups, supporting albumin as one contributor to lower measured circulating zinc. Condition category: biomarker_context nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower carrier-protein level can help explain a lower plasma zinc reading. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients limitations: Correlations cannot distinguish dietary shortage from albumin binding, redistribution and disease effects. Plasma measurements are not intracellular zinc thresholds. exposure: Fasting and post-meal plasma samples; disease-group comparisons. cross_nutrient: Human serum albumin (carrier_protein) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/walker1973.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "350425d75c9023c5b9ddb97d734e320b4e07c6fe5b834213defb1adc7cc26b00", "utf8_bytes": 991} [zn-clin-walker1973] Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis. (1973). https://pubmed.ncbi.nlm.nih.gov/4785284/ DOI: 10.1136/gut.14.12.943
Complete structured claim and evidence
Urinary zinc excretion was increased in cirrhosis but not in malabsorption, although both groups had low plasma zinc.
Zinc → Urinary zinc excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/walker1973.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "350425d75c9023c5b9ddb97d734e320b4e07c6fe5b834213defb1adc7cc26b00", "utf8_bytes": 991}
experimental_model
Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients
exposure
Fasting and post-meal plasma samples; disease-group comparisons.
limitations
Correlations cannot distinguish dietary shortage from albumin binding, redistribution and disease effects. Plasma measurements are not intracellular zinc thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Similar plasma results did not imply the same route of zinc loss.
primary_references
[zn-clin-walker1973] Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis. (1973). https://pubmed.ncbi.nlm.nih.gov/4785284/ DOI: 10.1136/gut.14.12.943
tissue_or_cell_type
Plasma and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1467–1480
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients · source_derived_draft · unverified_draft
### zn-clin-urinary-loss Urinary zinc excretion was increased in cirrhosis but not in malabsorption, although both groups had low plasma zinc. Condition category: biomarker_context nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Similar plasma results did not imply the same route of zinc loss. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Observational comparison of 19 malabsorption patients, 21 cirrhosis patients, 20 controls and 23 other disease patients limitations: Correlations cannot distinguish dietary shortage from albumin binding, redistribution and disease effects. Plasma measurements are not intracellular zinc thresholds. exposure: Fasting and post-meal plasma samples; disease-group comparisons. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/walker1973.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "350425d75c9023c5b9ddb97d734e320b4e07c6fe5b834213defb1adc7cc26b00", "utf8_bytes": 991} [zn-clin-walker1973] Plasma and urinary zinc in patients with malabsorption syndromes or hepatic cirrhosis. (1973). https://pubmed.ncbi.nlm.nih.gov/4785284/ DOI: 10.1136/gut.14.12.943
Complete structured claim and evidence
Zinc reduced continued-diarrhea risk by 23% (95% CI 12–32%); the reduction was 7% (−9 to 22%) on days 1–3 and 38% (27–48%) thereafter. Starting within three days reduced episodes lasting over seven days by 39% (7–61%).
Zinc → Child diarrheal illness days source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sazawal1995.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "8c21c0c3ec6dedca7f245298445dfe9f71d64ff618734cd66b0eac35952c5bc8", "utf8_bytes": 2090}
experimental_model
Double-blind randomized controlled trial in 937 children aged 6–35 months in New Delhi
exposure
20 mg elemental zinc/day; all children received oral rehydration and vitamin supplements.
limitations
Not every child had confirmed zinc deficiency. Specific zinc salt is not verified from abstract; efficacy belongs to this regimen and background care.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The zinc group recovered sooner, with differences depending on treatment timing.
primary_references
[zn-clin-sazawal1995] Zinc supplementation in young children with acute diarrhea in India. (1995). https://pubmed.ncbi.nlm.nih.gov/7651474/ DOI: 10.1056/nejm199509283331304
tissue_or_cell_type
Acute diarrheal illness
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1482–1495
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized controlled trial in 937 children aged 6–35 months in New Delhi · source_derived_draft · unverified_draft
### zn-clin-diarrhea-duration Zinc reduced continued-diarrhea risk by 23% (95% CI 12–32%); the reduction was 7% (−9 to 22%) on days 1–3 and 38% (27–48%) thereafter. Starting within three days reduced episodes lasting over seven days by 39% (7–61%). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The zinc group recovered sooner, with differences depending on treatment timing. organism: Homo sapiens tissue_or_cell_type: Acute diarrheal illness experimental_model: Double-blind randomized controlled trial in 937 children aged 6–35 months in New Delhi limitations: Not every child had confirmed zinc deficiency. Specific zinc salt is not verified from abstract; efficacy belongs to this regimen and background care. exposure: 20 mg elemental zinc/day; all children received oral rehydration and vitamin supplements. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sazawal1995.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "8c21c0c3ec6dedca7f245298445dfe9f71d64ff618734cd66b0eac35952c5bc8", "utf8_bytes": 2090} [zn-clin-sazawal1995] Zinc supplementation in young children with acute diarrhea in India. (1995). https://pubmed.ncbi.nlm.nih.gov/7651474/ DOI: 10.1056/nejm199509283331304
Complete structured claim and evidence
Mean watery stools per day fell by 39% (95% CI 6–70%; P=.02), and days with watery diarrhea by 21% (10–31%) in the zinc group. Benefits were larger in stunted children.
Zinc → Child watery stool frequency source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Child diarrheal illness days (additional_endpoint)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sazawal1995.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "8c21c0c3ec6dedca7f245298445dfe9f71d64ff618734cd66b0eac35952c5bc8", "utf8_bytes": 2090}
experimental_model
Double-blind randomized controlled trial in 937 children aged 6–35 months in New Delhi
exposure
20 mg elemental zinc/day; all children received oral rehydration and vitamin supplements.
limitations
Not every child had confirmed zinc deficiency. Specific zinc salt is not verified from abstract; efficacy belongs to this regimen and background care.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The trial found fewer watery stools as well as shorter illness.
primary_references
[zn-clin-sazawal1995] Zinc supplementation in young children with acute diarrhea in India. (1995). https://pubmed.ncbi.nlm.nih.gov/7651474/ DOI: 10.1056/nejm199509283331304
tissue_or_cell_type
Acute diarrheal illness
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1497–1510
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized controlled trial in 937 children aged 6–35 months in New Delhi · source_derived_draft · unverified_draft
### zn-clin-diarrhea-stools Mean watery stools per day fell by 39% (95% CI 6–70%; P=.02), and days with watery diarrhea by 21% (10–31%) in the zinc group. Benefits were larger in stunted children. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial found fewer watery stools as well as shorter illness. organism: Homo sapiens tissue_or_cell_type: Acute diarrheal illness experimental_model: Double-blind randomized controlled trial in 937 children aged 6–35 months in New Delhi limitations: Not every child had confirmed zinc deficiency. Specific zinc salt is not verified from abstract; efficacy belongs to this regimen and background care. exposure: 20 mg elemental zinc/day; all children received oral rehydration and vitamin supplements. cross_nutrient: Child diarrheal illness days (additional_endpoint) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sazawal1995.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "8c21c0c3ec6dedca7f245298445dfe9f71d64ff618734cd66b0eac35952c5bc8", "utf8_bytes": 2090} [zn-clin-sazawal1995] Zinc supplementation in young children with acute diarrhea in India. (1995). https://pubmed.ncbi.nlm.nih.gov/7651474/ DOI: 10.1056/nejm199509283331304
Complete structured claim and evidence
Diarrhea beyond five days occurred in 6.5%, 7.7% and 7.2% of the 20, 10 and 5 mg groups. The lower doses met the four-percentage-point noninferiority margin; stool counts also met the two-stool margin.
Zinc sulfate → Child diarrheal illness days source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Total loose or watery stools after enrollment (co_primary_endpoint)
evidence_location
Indexed primary abstract; accessible manuscript Methods and Results also inspected.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/dhingra2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "48deafc698125c49384f5678bf65f3af2a4fc3359510f29a9a94a6b4991ee03e", "utf8_bytes": 2238}
experimental_model
Double-blind randomized multicenter noninferiority trial in 4500 children aged 6–59 months in India and Tanzania
exposure
5, 10 or 20 mg zinc/day using zinc sulfate for 14 days.
limitations
Active-dose comparisons without a placebo arm. Noninferiority depends on the prespecified margin; not proof that doses are identical. Historical regimens are not current dosing guidance.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The tested lower doses preserved trial-defined efficacy.
primary_references
[zn-clin-dhingra2020] Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32966722/ DOI: 10.1056/nejmoa1915905
published_estimates
10 versus 20 mg: risk difference 1.2 percentage points, upper 98.75% CI 3.3; 5 versus 20 mg: 0.7, upper 2.8. Mean stools 10.7, 10.9, 10.8 (20,10,5 mg); reported differences 0.3 (upper 1.0) and 0.1 (upper 0.8). Indexed published version used; source-version differences retained in paper notes.
tissue_or_cell_type
Acute diarrheal illness and vomiting
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1512–1526
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized multicenter noninferiority trial in 4500 children aged 6–59 months in India and Tanzania · source_derived_draft · unverified_draft
### zn-clin-diarrhea-dose-efficacy Diarrhea beyond five days occurred in 6.5%, 7.7% and 7.2% of the 20, 10 and 5 mg groups. The lower doses met the four-percentage-point noninferiority margin; stool counts also met the two-stool margin. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested lower doses preserved trial-defined efficacy. organism: Homo sapiens tissue_or_cell_type: Acute diarrheal illness and vomiting experimental_model: Double-blind randomized multicenter noninferiority trial in 4500 children aged 6–59 months in India and Tanzania limitations: Active-dose comparisons without a placebo arm. Noninferiority depends on the prespecified margin; not proof that doses are identical. Historical regimens are not current dosing guidance. exposure: 5, 10 or 20 mg zinc/day using zinc sulfate for 14 days. cross_nutrient: Total loose or watery stools after enrollment (co_primary_endpoint) evidence_location: Indexed primary abstract; accessible manuscript Methods and Results also inspected. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/dhingra2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "48deafc698125c49384f5678bf65f3af2a4fc3359510f29a9a94a6b4991ee03e", "utf8_bytes": 2238} published_estimates: 10 versus 20 mg: risk difference 1.2 percentage points, upper 98.75% CI 3.3; 5 versus 20 mg: 0.7, upper 2.8. Mean stools 10.7, 10.9, 10.8 (20,10,5 mg); reported differences 0.3 (upper 1.0) and 0.1 (upper 0.8). Indexed published version used; source-version differences retained in paper notes. [zn-clin-dhingra2020] Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32966722/ DOI: 10.1056/nejmoa1915905
Complete structured claim and evidence
Vomiting within 30 minutes occurred in 19.3%, 15.6% and 13.7% of children at 20, 10 and 5 mg respectively; relative risks versus 20 mg were 0.81 (97.5% CI .67–.96) and .71 (.59–.86).
Zinc sulfate → Vomiting after an administered dose source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract; accessible manuscript Methods and Results also inspected.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/dhingra2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "48deafc698125c49384f5678bf65f3af2a4fc3359510f29a9a94a6b4991ee03e", "utf8_bytes": 2238}
experimental_model
Double-blind randomized multicenter noninferiority trial in 4500 children aged 6–59 months in India and Tanzania
exposure
5, 10 or 20 mg zinc/day using zinc sulfate for 14 days.
limitations
Active-dose comparisons without a placebo arm. Noninferiority depends on the prespecified margin; not proof that doses are identical. Historical regimens are not current dosing guidance.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Lower doses caused less vomiting in this trial.
primary_references
[zn-clin-dhingra2020] Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32966722/ DOI: 10.1056/nejmoa1915905
tissue_or_cell_type
Acute diarrheal illness and vomiting
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1528–1541
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized multicenter noninferiority trial in 4500 children aged 6–59 months in India and Tanzania · source_derived_draft · unverified_draft
### zn-clin-diarrhea-dose-vomiting Vomiting within 30 minutes occurred in 19.3%, 15.6% and 13.7% of children at 20, 10 and 5 mg respectively; relative risks versus 20 mg were 0.81 (97.5% CI .67–.96) and .71 (.59–.86). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower doses caused less vomiting in this trial. organism: Homo sapiens tissue_or_cell_type: Acute diarrheal illness and vomiting experimental_model: Double-blind randomized multicenter noninferiority trial in 4500 children aged 6–59 months in India and Tanzania limitations: Active-dose comparisons without a placebo arm. Noninferiority depends on the prespecified margin; not proof that doses are identical. Historical regimens are not current dosing guidance. exposure: 5, 10 or 20 mg zinc/day using zinc sulfate for 14 days. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract; accessible manuscript Methods and Results also inspected. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/dhingra2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "48deafc698125c49384f5678bf65f3af2a4fc3359510f29a9a94a6b4991ee03e", "utf8_bytes": 2238} [zn-clin-dhingra2020] Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial. (2020). https://pubmed.ncbi.nlm.nih.gov/32966722/ DOI: 10.1056/nejmoa1915905
Complete structured claim and evidence
Mean overall cold duration was 4.0 days with zinc versus 7.1 with placebo (P<.0001); cough lasted 2.1 versus 5.0 days and nasal discharge 3.0 versus 4.5 days.
Zinc acetate → Common cold symptom duration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/prasad2008.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "fbee9b28c3866295933e0baab1770cdaab0b62567ec2787a587522e493051b6e", "utf8_bytes": 1456}
experimental_model
Double-blind randomized placebo-controlled trial in 50 adults enrolled within 24 hours of cold onset
exposure
One lozenge with 13.3 mg elemental zinc as acetate every 2–3 hours while awake.
limitations
Small trial with subjective symptoms; biomarker differences do not prove the proposed antioxidant or anti-inflammatory pathway mediates benefit.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
This small acetate-lozenge trial found shorter symptoms.
primary_references
[zn-clin-prasad2008] Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate. (2008). https://pubmed.ncbi.nlm.nih.gov/18279051/ DOI: 10.1086/528803
tissue_or_cell_type
Upper respiratory symptoms
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1543–1556
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled trial in 50 adults enrolled within 24 hours of cold onset · source_derived_draft · unverified_draft
### zn-clin-cold-duration-positive Mean overall cold duration was 4.0 days with zinc versus 7.1 with placebo (P<.0001); cough lasted 2.1 versus 5.0 days and nasal discharge 3.0 versus 4.5 days. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: This small acetate-lozenge trial found shorter symptoms. organism: Homo sapiens tissue_or_cell_type: Upper respiratory symptoms experimental_model: Double-blind randomized placebo-controlled trial in 50 adults enrolled within 24 hours of cold onset limitations: Small trial with subjective symptoms; biomarker differences do not prove the proposed antioxidant or anti-inflammatory pathway mediates benefit. exposure: One lozenge with 13.3 mg elemental zinc as acetate every 2–3 hours while awake. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/prasad2008.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "fbee9b28c3866295933e0baab1770cdaab0b62567ec2787a587522e493051b6e", "utf8_bytes": 1456} [zn-clin-prasad2008] Duration and severity of symptoms and levels of plasma interleukin-1 receptor antagonist, soluble tumor necrosis factor receptor, and adhesion molecules in patients with common cold treated with zinc acetate. (2008). https://pubmed.ncbi.nlm.nih.gov/18279051/ DOI: 10.1086/528803
Complete structured claim and evidence
The tested commercial lozenge did not significantly improve ten-day recovery: zinc/placebo recovery-rate ratio .68 (95% CI .42–1.08; P=.10).
Zinc acetate → Common cold recovery rate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract; accessible manuscript Methods and Results also inspected.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hemila2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "581a713c4eeae243c2c96cb508cfe731318175d77c781476575775c09b6e9913", "utf8_bytes": 2004}
experimental_model
Double-blind randomized placebo-controlled Finnish trial: 253 packages allocated; 87 colds analyzed
exposure
Commercial acetate lozenges: 13 mg elemental zinc, six times daily, at most five days; nominal 78 mg/day.
limitations
This specific formulation dissolved in about eight minutes. Authors extended planned seven-day recovery analysis to ten days after finding no significant difference. Results do not identify why other formulations differ.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
A different acetate-lozenge regimen did not show faster recovery.
primary_references
[zn-clin-hemila2020] Zinc acetate lozenges for the treatment of the common cold: a randomised controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31980506/ DOI: 10.1136/bmjopen-2019-031662
tissue_or_cell_type
Upper respiratory symptoms and tolerability
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1558–1571
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled Finnish trial: 253 packages allocated; 87 colds analyzed · source_derived_draft · unverified_draft
### zn-clin-cold-recovery-null The tested commercial lozenge did not significantly improve ten-day recovery: zinc/placebo recovery-rate ratio .68 (95% CI .42–1.08; P=.10). Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different acetate-lozenge regimen did not show faster recovery. organism: Homo sapiens tissue_or_cell_type: Upper respiratory symptoms and tolerability experimental_model: Double-blind randomized placebo-controlled Finnish trial: 253 packages allocated; 87 colds analyzed limitations: This specific formulation dissolved in about eight minutes. Authors extended planned seven-day recovery analysis to ten days after finding no significant difference. Results do not identify why other formulations differ. exposure: Commercial acetate lozenges: 13 mg elemental zinc, six times daily, at most five days; nominal 78 mg/day. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract; accessible manuscript Methods and Results also inspected. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hemila2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "581a713c4eeae243c2c96cb508cfe731318175d77c781476575775c09b6e9913", "utf8_bytes": 2004} [zn-clin-hemila2020] Zinc acetate lozenges for the treatment of the common cold: a randomised controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31980506/ DOI: 10.1136/bmjopen-2019-031662
Complete structured claim and evidence
No adverse effects were reported by 37% of zinc recipients compared with 69% of placebo recipients. Taste was a prominent tolerability issue.
Zinc acetate → Adverse effects during zinc lozenge use source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc exposure and the specifically measured response.
evidence_location
Indexed primary abstract; accessible manuscript Methods and Results also inspected.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hemila2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "581a713c4eeae243c2c96cb508cfe731318175d77c781476575775c09b6e9913", "utf8_bytes": 2004}
experimental_model
Double-blind randomized placebo-controlled Finnish trial: 253 packages allocated; 87 colds analyzed
exposure
Commercial acetate lozenges: 13 mg elemental zinc, six times daily, at most five days; nominal 78 mg/day.
limitations
This specific formulation dissolved in about eight minutes. Authors extended planned seven-day recovery analysis to ten days after finding no significant difference. Results do not identify why other formulations differ.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The zinc lozenge caused more reported side effects.
primary_references
[zn-clin-hemila2020] Zinc acetate lozenges for the treatment of the common cold: a randomised controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31980506/ DOI: 10.1136/bmjopen-2019-031662
tissue_or_cell_type
Upper respiratory symptoms and tolerability
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1573–1586
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized placebo-controlled Finnish trial: 253 packages allocated; 87 colds analyzed · source_derived_draft · unverified_draft
### zn-clin-cold-tolerability No adverse effects were reported by 37% of zinc recipients compared with 69% of placebo recipients. Taste was a prominent tolerability issue. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The zinc lozenge caused more reported side effects. organism: Homo sapiens tissue_or_cell_type: Upper respiratory symptoms and tolerability experimental_model: Double-blind randomized placebo-controlled Finnish trial: 253 packages allocated; 87 colds analyzed limitations: This specific formulation dissolved in about eight minutes. Authors extended planned seven-day recovery analysis to ten days after finding no significant difference. Results do not identify why other formulations differ. exposure: Commercial acetate lozenges: 13 mg elemental zinc, six times daily, at most five days; nominal 78 mg/day. cross_nutrient: Zinc exposure and the specifically measured response. evidence_location: Indexed primary abstract; accessible manuscript Methods and Results also inspected. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hemila2020.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "581a713c4eeae243c2c96cb508cfe731318175d77c781476575775c09b6e9913", "utf8_bytes": 2004} [zn-clin-hemila2020] Zinc acetate lozenges for the treatment of the common cold: a randomised controlled trial. (2020). https://pubmed.ncbi.nlm.nih.gov/31980506/ DOI: 10.1136/bmjopen-2019-031662
Complete structured claim and evidence
SLC19A2 mRNA fell 76% and THTR-1 protein 77% under high glucose.
D-glucose → Human thiamine transporter 1 / SLC19A2 source_derived_draftungraded
Experimental context and source evidence
curation_topic
thiamine · Thiamine (vitamin B1)
experimental_condition
5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Transporter abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human primary proximal-tubule epithelial cells; 5-day culture
limitations
Cell culture; does not by itself establish patient-level thiamine loss.
primary_references
Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
Diabetes cascade: targeted primary-source supplement · lines 18–18
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft
SLC19A2 mRNA fell 76% and THTR-1 protein 77% under high glucose. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Cell culture; does not by itself establish patient-level thiamine loss. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
Complete structured claim and evidence
SLC19A3 mRNA fell 53% and THTR-2 protein 83% under high glucose.
D-glucose → Human thiamine transporter 2 / SLC19A3 source_derived_draftungraded
Experimental context and source evidence
curation_topic
thiamine · Thiamine (vitamin B1)
experimental_condition
5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Transporter abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human primary proximal-tubule epithelial cells; 5-day culture
limitations
Cell culture; does not by itself establish patient-level thiamine loss.
primary_references
Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
Diabetes cascade: targeted primary-source supplement · lines 21–21
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft
SLC19A3 mRNA fell 53% and THTR-2 protein 83% under high glucose. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Cell culture; does not by itself establish patient-level thiamine loss. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
Complete structured claim and evidence
High glucose reduced apical-to-basolateral thiamine transport across proximal-tubule monolayers by 37%.
D-glucose → Human proximal-tubule thiamine reabsorption source_derived_draftungraded
Experimental context and source evidence
curation_topic
thiamine · Thiamine (vitamin B1)
experimental_condition
5 mM glucose 26 mM glucose · D-glucose Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "26 mM glucose", "comparator": "5 mM glucose", "endpoint": "Directional thiamine transport", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "glucose", "state": "26 mM glucose"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human primary proximal-tubule epithelial cells; 5-day culture
limitations
Transport assay; transporter-expression changes accompany the effect without proving exclusive mediation.
primary_references
Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
Diabetes cascade: targeted primary-source supplement · lines 24–24
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human primary proximal-tubule epithelial cells; 5-day culture · source_derived_draft · unverified_draft
High glucose reduced apical-to-basolateral thiamine transport across proximal-tubule monolayers by 37%. Model: Human primary proximal-tubule epithelial cells; 5-day culture. Limits: Transport assay; transporter-expression changes accompany the effect without proving exclusive mediation. Primary reference: Larkin et al. 2012; DOI:10.1371/journal.pone.0053175; PMCID:PMC3532206; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053175
Complete structured claim and evidence
Renal thiamine clearance was 24-fold higher in type 1 and 16-fold higher in type 2 diabetes; plasma thiamine was 76% and 75% lower, respectively.
Human diabetes status in the specified observational comparison → Renal clearance of thiamine source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
curation_topic
thiamine · Thiamine (vitamin B1)
experimental_condition
Healthy control group Diabetes status · Human diabetes status in the specified observational comparison Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "Diabetes status", "comparator": "Healthy control group", "endpoint": "Renal thiamine clearance", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "human-diabetes-study-state", "state": "Diabetes status"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
26 type-1 and 48 type-2 patients versus 20 healthy controls
limitations
Cross-sectional association; not proof that dietary deficiency caused diabetes. Erythrocyte transporter changes complicate status assessment.
primary_references
Thornalley et al. 2007; PMID:17676306; PMCID:PMC1998885; https://pubmed.ncbi.nlm.nih.gov/17676306/
trigger_kind
biomarker_context Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 27–27
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · 26 type-1 and 48 type-2 patients versus 20 healthy controls · source_derived_draft · unverified_draft
Renal thiamine clearance was 24-fold higher in type 1 and 16-fold higher in type 2 diabetes; plasma thiamine was 76% and 75% lower, respectively. Model: 26 type-1 and 48 type-2 patients versus 20 healthy controls. Limits: Cross-sectional association; not proof that dietary deficiency caused diabetes. Erythrocyte transporter changes complicate status assessment. Primary reference: Thornalley et al. 2007; PMID:17676306; PMCID:PMC1998885; https://pubmed.ncbi.nlm.nih.gov/17676306/
Complete structured claim and evidence
GPX1-overexpressing mice showed reduced insulin-stimulated receptor phosphorylation in liver and Akt phosphorylation in liver and soleus.
Mouse Gpx1 overexpression genotype → Mouse insulin receptor / Insr source_derived_draftungraded
Experimental context and source evidence
curation_topic
selenium · Selenium
experimental_condition
Wild-type mice on the same diet GPX1 overexpression · Mouse Gpx1 overexpression genotype Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "GPX1 overexpression", "comparator": "Wild-type mice on the same diet", "endpoint": "Insulin-stimulated phosphorylation", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "mouse-gpx1-overexpression", "state": "GPX1 overexpression"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Male transgenic mice; selenium-adequate 0.4 mg/kg diet, ages 8 to 24 weeks
limitations
Overexpression experiment, not dietary selenium excess. Excess ROS quenching is a proposed explanation rather than a measured universal mechanism.
primary_references
McClung et al. 2004; DOI:10.1073/pnas.0308096101; PMID:15184668; https://pmc.ncbi.nlm.nih.gov/articles/PMC428436/
Diabetes cascade: targeted primary-source supplement · lines 30–30
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Male transgenic mice; selenium-adequate 0.4 mg/kg diet, ages 8 to 24 weeks · source_derived_draft · unverified_draft
GPX1-overexpressing mice showed reduced insulin-stimulated receptor phosphorylation in liver and Akt phosphorylation in liver and soleus. Model: Male transgenic mice; selenium-adequate 0.4 mg/kg diet, ages 8 to 24 weeks. Limits: Overexpression experiment, not dietary selenium excess. Excess ROS quenching is a proposed explanation rather than a measured universal mechanism. Primary reference: McClung et al. 2004; DOI:10.1073/pnas.0308096101; PMID:15184668; https://pmc.ncbi.nlm.nih.gov/articles/PMC428436/
Complete structured claim and evidence
GPX1-overexpressing mice had a smaller blood-glucose fall after insulin challenge and developed hyperglycemia, hyperinsulinemia and greater adiposity.
Mouse Gpx1 overexpression genotype → Mouse blood-glucose fall after insulin challenge source_derived_draftungraded
Experimental context and source evidence
curation_topic
selenium · Selenium
experimental_condition
Wild-type mice GPX1 overexpression · Mouse Gpx1 overexpression genotype Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "GPX1 overexpression", "comparator": "Wild-type mice", "endpoint": "Glucose fall after insulin", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "mouse-gpx1-overexpression", "state": "GPX1 overexpression"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Male transgenic mice on selenium-adequate diet, evaluated at 24 weeks
limitations
Does not establish that suppressing GPX1 is beneficial in other settings.
primary_references
McClung et al. 2004; DOI:10.1073/pnas.0308096101; PMID:15184668; https://pmc.ncbi.nlm.nih.gov/articles/PMC428436/
Diabetes cascade: targeted primary-source supplement · lines 33–33
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Male transgenic mice on selenium-adequate diet, evaluated at 24 weeks · source_derived_draft · unverified_draft
GPX1-overexpressing mice had a smaller blood-glucose fall after insulin challenge and developed hyperglycemia, hyperinsulinemia and greater adiposity. Model: Male transgenic mice on selenium-adequate diet, evaluated at 24 weeks. Limits: Does not establish that suppressing GPX1 is beneficial in other settings. Primary reference: McClung et al. 2004; DOI:10.1073/pnas.0308096101; PMID:15184668; https://pmc.ncbi.nlm.nih.gov/articles/PMC428436/
Complete structured claim and evidence
Wild-type mice fed thiamine-deficient diet for 10 days had higher plasma glucose, hepatic glucose and hepatic glycogen.
Thiamine (vitamin B1) → Plasma glucose concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
curation_topic
thiamine · Thiamine (vitamin B1)
experimental_condition
5 mg/kg control diet 0 mg/kg added thiamine diet · Thiamine (vitamin B1) Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "0 mg/kg added thiamine diet", "comparator": "5 mg/kg control diet", "endpoint": "Plasma glucose", "effect_direction": "increase", "combination": "single", "conditions": [{"entity_slug": "thiamine", "state": "0 mg/kg added thiamine diet"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment
limitations
A separate dietary arm of the OCT1 paper; not a berberine exposure experiment or direct proof of human diabetes causation.
primary_references
OCT1 cardiometabolic study 2018; DOI:10.1371/journal.pbio.2002907; PMID:29659562; https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002907
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 36–36
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment · source_derived_draft · unverified_draft
Wild-type mice fed thiamine-deficient diet for 10 days had higher plasma glucose, hepatic glucose and hepatic glycogen. Model: Mouse dietary experiment, figure 5; 16-hour fast before sampling; n=4 per genotype/treatment. Limits: A separate dietary arm of the OCT1 paper; not a berberine exposure experiment or direct proof of human diabetes causation. Primary reference: OCT1 cardiometabolic study 2018; DOI:10.1371/journal.pbio.2002907; PMID:29659562; https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2002907
Complete structured claim and evidence
Vascular specimens from patients with type 2 diabetes showed lower ATP7A protein.
Human vascular specimens from patients with type 2 diabetes → Human copper-transporting ATPase ATP7A source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
curation_topic
copper · Copper
experimental_condition
Control vascular specimens Type 2 diabetes vascular specimens · Human vascular specimens from patients with type 2 diabetes Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "Type 2 diabetes vascular specimens", "comparator": "Control vascular specimens", "endpoint": "ATP7A protein abundance", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "human-t2d-vessel-state", "state": "Type 2 diabetes vascular specimens"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Human vascular specimens; primary abstract reviewed
limitations
Observational human finding; detailed sampling and covariate analysis require full-methods review.
primary_references
Sudhahar et al. 2018; DOI:10.1161/ATVBAHA.117.309819; PMID:29301787; https://pubmed.ncbi.nlm.nih.gov/29301787/
trigger_kind
biomarker_context Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 39–39
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Human vascular specimens; primary abstract reviewed · source_derived_draft · unverified_draft
Vascular specimens from patients with type 2 diabetes showed lower ATP7A protein. Model: Human vascular specimens; primary abstract reviewed. Limits: Observational human finding; detailed sampling and covariate analysis require full-methods review. Primary reference: Sudhahar et al. 2018; DOI:10.1161/ATVBAHA.117.309819; PMID:29301787; https://pubmed.ncbi.nlm.nih.gov/29301787/
Complete structured claim and evidence
Akt2-null vessels or vascular smooth-muscle cells had lower SOD3 activity, rescued by ATP7A overexpression.
Mouse Akt2-null genotype → Mouse extracellular superoxide dismutase Sod3 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
curation_topic
copper · Copper
experimental_condition
Control; ATP7A overexpression tested as rescue Akt2 loss · Mouse Akt2-null genotype Condition belongs to the full experimental contrast; do not separate a joint intervention.
experimental_contrast
{"intervention": "Akt2 loss", "comparator": "Control; ATP7A overexpression tested as rescue", "endpoint": "SOD3 activity", "effect_direction": "decrease", "combination": "single", "conditions": [{"entity_slug": "mouse-akt2-null", "state": "Akt2 loss"}]} Explicit extracted experimental comparison; source-derived draft.
experimental_model
Mouse Akt2-null vascular experiments; primary abstract reviewed
limitations
Genetic signaling defect, not dietary copper deficiency. Mechanistic phosphorylation experiments are not substituted for human causal evidence.
primary_references
Sudhahar et al. 2018; DOI:10.1161/ATVBAHA.117.309819; PMID:29301787; https://pubmed.ncbi.nlm.nih.gov/29301787/
trigger_kind
machinery_impairment Imported condition classification; unverified.
Diabetes cascade: targeted primary-source supplement · lines 42–42
See claim-local references; curated paraphrases reviewed 2026-09-20. · supports · Mouse Akt2-null vascular experiments; primary abstract reviewed · source_derived_draft · unverified_draft
Akt2-null vessels or vascular smooth-muscle cells had lower SOD3 activity, rescued by ATP7A overexpression. Model: Mouse Akt2-null vascular experiments; primary abstract reviewed. Limits: Genetic signaling defect, not dietary copper deficiency. Mechanistic phosphorylation experiments are not substituted for human causal evidence. Primary reference: Sudhahar et al. 2018; DOI:10.1161/ATVBAHA.117.309819; PMID:29301787; https://pubmed.ncbi.nlm.nih.gov/29301787/
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

Adaptive ZIP4 expression during dietary zinc deficiency

Condition: nutrient_deficiency · Experimental zinc-deficient diet

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: ZIP4 transcript persists longer

Scope: Mus musculus; Defined zinc-deficient versus adequate diets; transcription assessed after 24 hours from gestational day 8.

Across approximately 150,000 people, carriers of 12 rare SLC30A8 truncating variants had 65% lower type 2 diabetes risk.

Condition: machinery_impairment · Truncating-variant carrier

Normal role: Read the matched control and canonical normal-mechanism records; this scenario does not infer the reverse relationship.

Recorded consequence: Across approximately 150,000 people, carriers of 12 rare SLC30A8 truncating variants had 65% lower type 2 diabetes risk.

Scope: Human genetic association across five ancestry groups

ZIP4 response to zinc repletion after dietary depletion

Condition: nutrient_deficiency · Zinc gavage following zinc-deficient feeding

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: Less ZIP4 remains at the apical membrane

Scope: Mus musculus; Zinc-deficient weanlings for 10 days; 100 micromol ZnCl2/kg oral gavage with time-course localization.

SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation.

Condition: machinery_impairment · SLC30A8 knockout

Normal role: Read the matched control and canonical normal-mechanism records; this scenario does not infer the reverse relationship.

Recorded consequence: SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation.

Scope: Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed

Intestinal ZIP4 loss depletes systemic tissue zinc

Condition: machinery_impairment · Enterocyte-specific Slc39a4 deletion

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: Total tissue zinc rapidly declines Total tissue zinc rapidly declines Hepatic iron, manganese and copper accumulated as disease progressed.

Scope: Mus musculus; Conditional gene deletion compared with intact controls.

SLC30A8-null and R138X beta cells had fewer crystalline insulin granules; glucose-stimulated secretion was not impaired in the tested system.

Condition: machinery_impairment · SLC30A8-null or R138X cells

Normal role: Read the matched control and canonical normal-mechanism records; this scenario does not infer the reverse relationship.

Recorded consequence: SLC30A8-null and R138X beta cells had fewer crystalline insulin granules; glucose-stimulated secretion was not impaired in the tested system.

Scope: Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed

H54R ZnT2 trafficking defect

Condition: machinery_impairment · H54R amino-acid substitution

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: Abnormal localization and reduced cellular zinc secretion

Scope: Homo sapiens; H54R compared with wild-type ZnT2.

After 5 micromolar TPEN for 48 hours, apoptosis was lower in SLC30A8-null and R138X cells than treated wild-type cells.

Condition: machinery_impairment · ZnT8 loss plus TPEN

Normal role: Read the matched control and canonical normal-mechanism records; this scenario does not infer the reverse relationship.

Recorded consequence: After 5 micromolar TPEN for 48 hours, apoptosis was lower in SLC30A8-null and R138X cells than treated wild-type cells.

Scope: Engineered human embryonic stem-cell-derived beta cells; results and figure 5 reviewed

H54R coexpression retains wild-type transport effect

Condition: machinery_impairment · Coexpression of H54R and intact ZnT2

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: No abolition of the wild-type secretion increase

Scope: Homo sapiens; H54R plus wild type compared with wild type alone.

W152R ZnT2 transport loss

Condition: machinery_impairment · W152R substitution identified in a compound-heterozygous mother

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: Loss of transport activity

Scope: Human protein in Gallus gallus cells; W152R compared with wild type; functional complementation and zinc-handling assays.

S296L ZnT2 instability

Condition: machinery_impairment · S296L amino-acid substitution

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: Less stable transporter despite retained intrinsic functions

Scope: Human protein in Gallus gallus cells; S296L variant compared with wild type.

Intestinal ZIP5 loss changes zinc distribution

Condition: machinery_impairment · Enterocyte-specific Zip5 deletion

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: More zinc accumulates in the pancreas

Scope: Mus musculus; Induced enterocyte deletion on zinc-adequate chow.

Acinar ZIP5 loss reduces zinc retention

Condition: machinery_impairment · Acinar-cell Slc39a5 deletion

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: Tracer zinc is retained less well

Scope: Mus musculus; Tracer zinc uptake and retention compared between acinar knockouts and controls.

ZIP5 protein decreases during zinc depletion

Condition: nutrient_deficiency · Experimental dietary zinc deficiency

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: ZIP5 is removed and degraded while transcript abundance remains stable

Scope: Mus musculus; Defined zinc-deficient diet followed in some experiments by oral zinc repletion.

When alcohol strips zinc from the gut barrier

Condition: nutrient_deficiency · Alcohol exposure, which lowers ileal zinc in association with reactive oxygen species accumulation.

Normal role: Zinc holds tight junction proteins together at the intestinal epithelium.

Recorded consequence: The ileal barrier leaks, tight junction proteins disassemble, and minor zinc deprivation makes the alcohol effect worse.

Scope: Mouse ileum and Caco-2 monolayers

Placental response to moderate maternal zinc restriction

Condition: nutrient_deficiency · 15 mg zinc/kg experimental diet versus adequate 50 mg/kg

Normal role: The intact transporter system regulates zinc movement and compartment availability.

Recorded consequence: Lower placental ZnT1 abundance

Scope: Mus musculus; 15 versus 50 mg zinc/kg diet from pregnancy onset to day 17; 150 mg/kg group also had lower expression than 50 mg/kg.

Maternal ZnT2 variants can restrict infant zinc supply

Condition: machinery_impairment · Impaired maternal ZnT2-associated milk zinc secretion

Normal role: Maternal milk supplies zinc to a breastfed infant.

Recorded consequence: Low milk zinc and neonatal zinc deficiency in reported families.

Scope: Human genetic case observations; cell functional tests retained separately.

Secretory zinc-loading machinery impairment

Condition: machinery_impairment · Genetic deficiency of the two specific secretory ZnT complexes, followed by zinc supplementation in culture; amount unreported in abstract.

Normal role: Specific ZnT complexes deliver zinc during TNAP maturation.

Recorded consequence: Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes.

Scope: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation

Secretory zinc-loading machinery impairment

Condition: machinery_impairment · Transport-incompetent ZnT5 variant reconstituted with ZnT6 in DT40 cells. Transport-incompetent ZnT5 variant with ZnT6, compared with functional loading machinery.

Normal role: Specific ZnT complexes deliver zinc during TNAP maturation.

Recorded consequence: A transport-incompetent ZnT5 variant expressed with ZnT6 stabilized TNAP protein as the apo form despite failing to restore enzyme activity. Reconstitution of ZnT5-ZnT6 with transport-incompetent ZnT5 did not restore TNAP activity.

Scope: Engineered chicken DT40 cells with ZnT gene disruption and transporter re-expression; TNAP activation

Experimental zinc deficiency reduces vitamin-phosphate hydrolysis

Condition: nutrient_deficiency · Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract.

Normal role: Zinc availability supports zinc-dependent ectoenzyme activity.

Recorded consequence: Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study.

Scope: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets

Experimental zinc deficiency reduces vitamin-phosphate hydrolysis

Condition: nutrient_deficiency · Rats fed zinc-deficient diets; dietary content and duration not available in the abstract.

Normal role: Zinc availability supports zinc-dependent ectoenzyme activity.

Recorded consequence: Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study.

Scope: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets

Without MTF1 the metallothionein response is lost

Condition: machinery_impairment · Mouse Mtf1 loss

Normal role: The recorded zinc-handling machinery supports the specified cellular function.

Recorded consequence: Basal and zinc-induced Mt1/Mt2 transcription fail

Scope: Genetic or cellular model as recorded in the primary claim.

Loss of ZIP10 disrupts B-cell signaling

Condition: machinery_impairment · ZIP10 deletion in mature mouse B cells

Normal role: The recorded zinc-handling machinery supports the specified cellular function.

Recorded consequence: CD45R activity falls, LYN signaling is dysregulated and antibody responses weaken

Scope: Genetic or cellular model as recorded in the primary claim.

Intestinal ZIP7 loss triggers endoplasmic-reticulum stress

Condition: machinery_impairment · ZIP7 loss in the indicated mouse intestinal cell lineage

Normal role: The recorded zinc-handling machinery supports the specified cellular function.

Recorded consequence: Crypt-cell stress, progenitor-cell loss and impaired renewal; phenotype depends on targeted lineage

Scope: Genetic or cellular model as recorded in the primary claim.

Chelating available zinc changes dendritic-cell maturation markers

Condition: nutrient_deficiency · Zinc availability reduced with a chelator in the experimental model

Normal role: Intracellular zinc distribution participates in cell-specific signaling regulation.

Recorded consequence: The chelator mimicked the reported LPS-associated response.

Scope: Mouse dendritic-cell experimental manipulation.

Dietary zinc restriction affects selected T-cell responses

Condition: nutrient_deficiency · Controlled experimental zinc restriction

Normal role: Adequate zinc availability supports the tested T-cell responses.

Recorded consequence: TH1-associated cytokine production decreased while the tested TH2 profile was unchanged.

Scope: Human experimental deficiency model; baseline, restriction and repletion sampled.

Manganese chelation can lower zinc

Condition: biomarker_context · Chelation in the reported SLC30A10 patient

Normal role: Nutrient availability and its transport machinery support the specifically measured function.

Recorded consequence: Zinc concentration fell during treatment.

Scope: The particular human, enzyme or cellular model specified in the linked claims.

Zinc depletion changed retinoid handling in the liver.

Condition: nutrient_deficiency · Pair-fed experimental zinc deficiency.

Normal role: Retinoid oxidation and storage occur through several hepatic pathways.

Recorded consequence: Different hepatic retinoid-oxidation activities changed in different directions.

Scope: Rat liver homogenate assays.

Low plasma zinc can reflect more than intake

Condition: biomarker_context · Sampling time, meals and cirrhosis or malabsorption context

Normal role: Plasma zinc is one measured circulating pool, partly related to albumin.

Recorded consequence: Plasma levels differ with timing and disease; albumin correlation complicates interpretation.

Scope: Observational human plasma and urine study.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Diabetes cascade: targeted primary-source supplementSee claim-local references; curated paraphrases reviewed 2026-09-20. · unverified_draftRead preserved source
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which zinc pool or repeated biomarker best predicts a specific cellular failure in an individual?Intake, circulating zinc, albumin, labile intracellular zinc and protein metallation are different quantities.
Which lozenge properties, contact time, formulation and population explain differing cold outcomes?The two trials differ in regimen and formulation. A negative result and a positive result under different conditions do not establish a single unresolved molecular contradiction.
What dose-duration and host factors predict copper depletion during zinc exposure?Case evidence and biomarker changes do not supply a universal zinc:copper supplement ratio.
Which secretory zinc-loading pathway supplies native human CA6?TNAP loading cannot be extrapolated to CA6 without a direct experiment.
Does correcting dietary zinc deficiency improve human B-vitamin absorption or clinical response through these ectoenzymes?The 2024 abstract reports cell-lysate and rat-serum hydrolysis, not a human absorption or treatment experiment.
How much oral zinc changes SOD1 maturation in an already zinc-replete person?The cell-expression and purified-protein experiments do not answer a supplementation question.
How do different intestinal exposures determine whether copper is retained on metallothionein or prevented from entering mucosal cells?Whole-animal feeding and perfused-intestine studies resolve different steps and concentrations; binding alone does not define net uptake.
Which local zinc pool and transporter defect determine whether nutrient repletion restores a specific cell function?Extracellular zinc did not rescue ZIP7-deficient organoid stress. This cannot be generalized to every transporter or dietary deficiency.
How much do calcium countertransport and proton-dependent transitions each contribute to human ZnT1 export in native tissues?Two 2024 primary studies emphasize different coupling models. Calcium-gradient effects and pH-dependent structures are retained separately; they do not by themselves quantify physiological flux or show that the routes are mutually exclusive.
How much of human renal zinc reabsorption and transplacental zinc transfer is specifically carried by ZIP8?The scoped primary evidence here measures mouse renal manganese transport and human placental-cell iron uptake, not native human zinc flux.
Does ZIP5-driven blood-to-enterocyte zinc entry quantitatively account for intestinal zinc excretion in humans?Basolateral localization and mouse knockout redistribution support this route but are not direct human excretion measurements.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Zinc

The mechanisms

CNNM2 coexpression increased TRPM7-dependent zinc influx, and the TRPM7 E1047K pore mutant prevented this increase.

Chemical zinc removal inactivated human BHMT; zinc reconstitution restored its activity and metal content.

Human GCPII crystal structures resolved two zinc ions at the catalytic center, bridged by water or hydroxide and Asp387.

Calcium at TNAP site M3 supported about 40% of the activity of Mg/Zn-TNAP at pH 7.4 and 9.8.

Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity.

Very high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH.

The same zinc-deficient rats showed increased retinal oxidase activity, with no detected REH/ARAT activity changes.

In women with low initial zinc, vitamin A plus zinc improved night-vision recovery versus double placebo; zinc alone did not.

Zinc increased plasma retinol and transthyretin versus placebo; the RBP increase was not significant.

The pooled high-zinc groups also had lower Mg balance.

ZnCl2 did not restore isomerohydrolase activity after metal chelation in the bovine RPE assay, whereas FeSO4 did.

Zinc-deficient rats had lower hepatic retinol-oxidizing ADH activity and greater hepatic vitamin A content.

Iron increased plasma retinol, RBP and transthyretin; the combined iron/zinc arm increased retinol without significant carrier-protein increases.

High-dose supplemental zinc reduced measured Mg absorption in the pooled metabolic-balance groups.

Across approximately 150,000 people, carriers of 12 rare SLC30A8 truncating variants had 65% lower type 2 diabetes risk.

SLC30A8 knockout elevated free cytosolic zinc, whereas R138X did not show the same significant elevation.

SLC30A8-null and R138X beta cells had fewer crystalline insulin granules; glucose-stimulated secretion was not impaired in the tested system.

After 5 micromolar TPEN for 48 hours, apoptosis was lower in SLC30A8-null and R138X cells than treated wild-type cells.

Expression of mouse ZIP4 increased zinc influx into transfected cells.

Dietary zinc deficiency increased mouse Zip4 mRNA by greater transcript stability rather than an increased relative transcription rate.

Oral zinc repletion caused mouse ZIP4 internalization from enterocyte apical membranes after dietary zinc deficiency.

Elevated zinc stimulated human ZIP4 ubiquitination and degradation; a cytoplasmic histidine-rich region was required for this degradation response but dispensable for zinc-induced endocytosis.

Enterocyte-specific Slc39a4 deletion rapidly lowered total zinc in mouse small intestine, liver and pancreas.

In reconstituted human ZnT1 proteoliposomes, a transmembrane calcium gradient accelerated zinc transport and zinc addition drove calcium countertransport. Zinc transport persisted at a lower rate without the calcium gradient.

Human ZnT1 purified with zinc at pH 6.0 yielded inward-facing, outward-facing and mixed dimers, whereas the pH 7.5 zinc-bound structure was outward-facing; the authors interpreted structures and simulations as supporting proton-dependent zinc release.

Human ZnT2 H54R expressed in HEK293 cells accumulated in perinuclear aggresomal structures and showed reduced zinc secretion.

Coexpressing human ZnT2 H54R with wild-type ZnT2 did not abolish the increased zinc secretion produced by wild-type ZnT2 overexpression alone.

Human ZnT2 W152R lost zinc transport activity in zinc-sensitive DT40 cells.

Human ZnT2 S296L retained zinc transport and dimer-forming capacity in the DT40 characterization but had markedly reduced protein stability.

Mouse ZIP5 expression increased cellular Zn(II) uptake and showed selectivity for zinc among the potential substrates tested.

Mouse ZIP5 localized to the basolateral membrane when expressed in polarized MDCK cells.

Enterocyte-specific Zip5 deletion increased pancreatic zinc in mice eating a zinc-adequate diet.

Pancreatic acinar-cell Zip5 deletion impaired retention of administered 67Zn despite no detected impairment of rapid pancreatic 67Zn accumulation.

During dietary zinc deficiency in mice, ZIP5 protein was internalized and degraded in enterocytes, pancreatic acinar cells and visceral endoderm even though Zip5 mRNA abundance did not change.

Rat ZIP8 expression in HEK293T cells increased radiolabeled zinc uptake by about 40% compared with empty-vector controls.

A tenfold molar excess of iron inhibited radiolabeled zinc uptake in HEK293T cells expressing rat ZIP8.

A tenfold molar excess of zinc inhibited iron uptake by more than 90% in rat ZIP8-expressing HEK293T cells under the study conditions.

Suppressing endogenous human ZIP8 in BeWo placental cells reduced iron uptake by approximately 40%.

Mouse ZIP14 expression in Xenopus oocytes supported saturable zinc uptake with an apparent half-maximal zinc concentration near 2 micromolar.

Mouse ZIP14 directly mediated 54Mn(II) uptake in RNA-injected Xenopus oocytes.

Zinc inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes.

Mouse ZIP14 did not increase uptake of radiolabeled copper supplied as Cu(I) or Cu(II) in the tested oocyte conditions.

ZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells.

Placental ZnT1 expression was lower in pregnant mice fed 15 mg zinc/kg diet than in those fed 50 mg/kg; the mRNA pattern was reflected at the protein level.

In the reported family, two exclusively breastfed infants developed zinc deficiency associated with low maternal milk zinc; affected mothers carried SLC30A2 H54R.

A mother carrying W152R and S296L on different SLC30A2 alleles had a reported greater-than-90% reduction in milk zinc; her breastfed infant developed severe zinc deficiency.

After enterocyte Zip4 deletion in mice, liver iron, manganese and copper gradually accumulated as the zinc-depletion disease progressed.

Chelating zinc from recombinant human CA2 reduced catalytic activity; the apo preparation retained about 10% residual zinc.

Adding 1 mM ZnCl2 revived the activity of chelated recombinant human CA2.

Zinc-containing CA2 unfolded at 59±0.5°C versus 51±0.5°C for the chelated preparation in differential scanning calorimetry.

The chelated human CA2 structure retained the overall protein fold relative to zinc-containing CA2.

X-ray absorption analysis of human CA2 supported a zinc site with three histidine nitrogen ligands and most likely one water/hydroxide oxygen ligand in both isolated and reconstituted enzyme.

Purified human salivary and milk CA6 catalyzed CO2 hydration, with reported kcat values of 3.3×10^5 and 2.3×10^5 s−1, respectively.

Acetazolamide inhibited salivary and milk human CA6 with reported Ki values of 16 and 23 nM in the enzyme assay.

In the purified human protein system, CCS domain 1 was necessary for loading SOD1 with Cu(I).

Human CCS domain 2 promoted the CCS-SOD1 heterodimer interaction required for copper loading in the in-vitro study.

Human CCS domain 3 catalyzed formation of the SOD1 Cys57-Cys146 disulfide through a transfer mechanism involving CCS Cys244 and Cys246.

Adding 10 µM ZnSO4 during human SOD1 expression in HEK293T cells promoted site-selective binding of one zinc ion per SOD1 subunit and the zinc-containing dimer.

Coexpression of CCS increased Cu(I) incorporation into SOD1 after Cu(II) exposure in zinc-supplemented HEK293T cells; at higher expression the Cu(I),Zn-SOD1:E,Zn-SOD1 ratio reached about 1:1.

In zinc-supplemented HEK293T cells, CCS coexpression promoted SOD1 disulfide oxidation without detectable additional SOD1 copper loading.

The ZnT5-ZnT6 and ZnT7 complexes support TNAP conversion from apoenzyme to zinc-loaded active enzyme in the early secretory pathway.

Extracellular zinc supplementation did not restore reduced TNAP activity in DT40 cells deficient in both ZnT5-ZnT6 and ZnT7 complexes.

A transport-incompetent ZnT5 variant expressed with ZnT6 stabilized TNAP protein as the apo form despite failing to restore enzyme activity.

Reconstitution of ZnT5-ZnT6 with transport-incompetent ZnT5 did not restore TNAP activity.

The recombinant TNAP mutant study attributed effects of disrupting calcium site M4 to protein structure rather than direct catalysis by M4-bound calcium.

Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study.

Serum from rats fed zinc-deficient diets showed reduced B-vitamin phosphate-ester hydrolysis activity in the study.

Mtf1-null mouse embryonic stem cells lacked detectable basal and zinc-induced Mt1 and Mt2 transcription.

Recombinant human and mouse MTF1 required added zinc for DNA binding; among the tested transition metals, only zinc activated recombinant MTF1 binding.

Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay.

Rat diets with zinc up to 450 mg/kg did not change 64Cu absorption; 900 mg/kg reduced it by about 40% and increased mucosal 64Cu uptake.

The increased intestinal 64Cu was predominantly metallothionein-associated; the authors inferred copper displacement of zinc after zinc-induced metallothionein synthesis.

Raising rat dietary copper from 3 to 24 mg/kg reduced 65Zn absorption by about 20%; further increases to 300 mg/kg did not add inhibition or change zinc association with intestinal metallothionein.

After the tested dietary conditioning, high zinc increased metallothionein-bound copper without changing intracellular copper concentration or significantly altering measured copper absorption in the perfused intestine.

High luminal zinc reduced both mucosal cytosolic copper and copper transfer into portal effluent in the perfused-rat-intestine experiments.

High luminal copper increased mucosal zinc accumulation while reducing zinc transfer to portal effluent at the highest luminal zinc concentration.

The study identified CK2-dependent phosphorylation of ZIP7 as a regulatory step preceding cytosolic zinc release from intracellular stores.

ZIP7 phosphorylation was linked to release of stored zinc and downstream AKT and ERK1/2 phosphorylation in the studied human cells.