Nutrient chapter

Copper

Copper; read each linked claim for the measured context and model.

127 recorded mechanisms · 21 availability situations · 8 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.

Human hephaestin catalyzed diferric transferrin formation from Fe(II) and apotransferrin in vitro.
Human hephaestin / HEPH → Human transferrin loaded with two ferric ions source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"}
experimental_model
Purified recombinant human hephaestin
exposure
Fe(II) substrate and apotransferrin assays
limitations
Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein produced in baby hamster kidney cells
plain_language
Copper-dependent iron processing helps load iron onto its blood carrier.
primary_references
[copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k
tissue_or_cell_type
Purified soluble hephaestin construct
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 780–791
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human hephaestin · source_derived_draft · unverified_draft
### copper-heph-transferrin-loading Human hephaestin catalyzed diferric transferrin formation from Fe(II) and apotransferrin in vitro. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper-dependent iron processing helps load iron onto its blood carrier. organism: Human protein produced in baby hamster kidney cells tissue_or_cell_type: Purified soluble hephaestin construct experimental_model: Purified recombinant human hephaestin limitations: Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry. exposure: Fe(II) substrate and apotransferrin assays evidence_span: {"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"} [copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k
Complete structured claim and evidence
Whole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues.
Mouse hephaestin Heph → Mouse circulating iron availability source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"}
experimental_model
Whole-body and intestine-specific Heph/Cp double-knockout mice
exposure
Combined or tissue-specific deletion; oral iron tracer
limitations
Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The body had iron, but much of it was in the wrong places.
primary_references
[copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
tissue_or_cell_type
Intestine, liver, heart, pancreas and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 819–830
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and intestine-specific Heph/Cp double-knockout mice · source_derived_draft · unverified_draft
### copper-heph-cp-low-blood-iron Whole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body had iron, but much of it was in the wrong places. organism: Mouse tissue_or_cell_type: Intestine, liver, heart, pancreas and blood experimental_model: Whole-body and intestine-specific Heph/Cp double-knockout mice limitations: Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route. exposure: Combined or tissue-specific deletion; oral iron tracer evidence_span: {"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"} [copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
Complete structured claim and evidence
Copper-deficient rats had enterocyte hephaestin protein at about 35% of copper-adequate controls.
Copper → Rat enterocyte hephaestin protein abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"}
experimental_model
Controlled copper-deficient versus adequate diets with radiolabeled iron
exposure
Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings
limitations
Animal depletion regimens are not human thresholds. Iron redistribution differed by sex.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat
plain_language
Copper shortage reduced part of the intestine’s iron-processing machinery.
primary_references
[copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
tissue_or_cell_type
Duodenal enterocytes and whole-body iron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 858–869
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled copper-deficient versus adequate diets with radiolabeled iron · source_derived_draft · unverified_draft
### copper-cud-hephaestin Copper-deficient rats had enterocyte hephaestin protein at about 35% of copper-adequate controls. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper shortage reduced part of the intestine’s iron-processing machinery. organism: Rat tissue_or_cell_type: Duodenal enterocytes and whole-body iron experimental_model: Controlled copper-deficient versus adequate diets with radiolabeled iron limitations: Animal depletion regimens are not human thresholds. Iron redistribution differed by sex. exposure: Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings evidence_span: {"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"} [copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
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
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
Human CTR1 supported high-affinity, saturable, metal-selective copper uptake at the plasma membrane.
Human high-affinity copper transporter CTR1 / SLC31A1 → Cellular copper uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/11734551.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c", "start_char": 0, "end_char": 1144, "text_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c"}
experimental_model
Human CTR1 expression and radiocopper transport assays
exposure
CTR1 expression; pH and potassium changes in culture
limitations
Transport kinetics in cells; elevated assay potassium is not evidence that potassium supplements improve human copper status.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein in human HEK293 cells
plain_language
CTR1 is a controlled entry route for copper into cells.
primary_references
[copper-p11734551] Biochemical characterization of the human copper transporter Ctr1. (2002). https://pubmed.ncbi.nlm.nih.gov/11734551/ DOI: 10.1074/jbc.m104728200
tissue_or_cell_type
Plasma membrane
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 247–258
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CTR1 expression and radiocopper transport assays · source_derived_draft · unverified_draft
### copper-ctr1-uptake Human CTR1 supported high-affinity, saturable, metal-selective copper uptake at the plasma membrane. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: CTR1 is a controlled entry route for copper into cells. organism: Human protein in human HEK293 cells tissue_or_cell_type: Plasma membrane experimental_model: Human CTR1 expression and radiocopper transport assays limitations: Transport kinetics in cells; elevated assay potassium is not evidence that potassium supplements improve human copper status. exposure: CTR1 expression; pH and potassium changes in culture evidence_span: {"source_cache": "artifacts/copper-research/11734551.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c", "start_char": 0, "end_char": 1144, "text_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c"} [copper-p11734551] Biochemical characterization of the human copper transporter Ctr1. (2002). https://pubmed.ncbi.nlm.nih.gov/11734551/ DOI: 10.1074/jbc.m104728200
Complete structured claim and evidence
Copper-loaded ATOX1 activated ATP7B ATP hydrolysis while changing interactions among its first three metal-binding domains.
Human copper chaperone ATOX1 → ATP7B ATP hydrolysis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/28900031.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8", "start_char": 0, "end_char": 1471, "text_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8"}
experimental_model
Biochemistry, solution NMR and small-angle X-ray scattering
exposure
Apo versus copper-loaded ATOX1
limitations
Domain motion and ATP hydrolysis were studied directly; these assays do not establish a whole-body copper requirement.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human proteins
plain_language
The courier also helps switch on the copper pump.
primary_references
[copper-p28900031] The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics. (2017). https://pubmed.ncbi.nlm.nih.gov/28900031/ DOI: 10.1074/jbc.m117.811752
tissue_or_cell_type
Purified ATOX1 and ATP7B domains
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 390–401
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemistry, solution NMR and small-angle X-ray scattering · source_derived_draft · unverified_draft
### copper-atox1-atp7b-activation Copper-loaded ATOX1 activated ATP7B ATP hydrolysis while changing interactions among its first three metal-binding domains. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The courier also helps switch on the copper pump. organism: Human proteins tissue_or_cell_type: Purified ATOX1 and ATP7B domains experimental_model: Biochemistry, solution NMR and small-angle X-ray scattering limitations: Domain motion and ATP hydrolysis were studied directly; these assays do not establish a whole-body copper requirement. exposure: Apo versus copper-loaded ATOX1 evidence_span: {"source_cache": "artifacts/copper-research/28900031.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8", "start_char": 0, "end_char": 1471, "text_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8"} [copper-p28900031] The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics. (2017). https://pubmed.ncbi.nlm.nih.gov/28900031/ DOI: 10.1074/jbc.m117.811752
Complete structured claim and evidence
Elesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells.
Elesclomol-copper complex → Mitochondrial cytochrome c oxidase / respiratory complex IV source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"}
experimental_model
Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria
exposure
Slc25a3 deletion and elesclomol-copper exposure
limitations
Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat H9c2 cells; human SLC25A3 in Lactococcus lactis
plain_language
Delivering more copper to the organelle did not ensure delivery to the enzyme.
primary_references
[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
tissue_or_cell_type
Mitochondria; bacterial copper export assay
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 559–570
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft
### copper-slc25a3-es-no-cox-rescue Elesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delivering more copper to the organelle did not ensure delivery to the enzyme. organism: Rat H9c2 cells; human SLC25A3 in Lactococcus lactis tissue_or_cell_type: Mitochondria; bacterial copper export assay experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
Complete structured claim and evidence
Glutathione reduced fully oxidized apo-COX17 back to the two-disulfide state in the protein-transfer system.
GSH → Human apo-COX17 with three disulfides source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"}
experimental_model
Purified-protein metal and electron transfer experiments
exposure
Defined COX17 and SCO redox states; glutathione reduction
limitations
Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human proteins
plain_language
Glutathione helps reset a mitochondrial copper courier.
primary_references
[copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
tissue_or_cell_type
Mitochondrial intermembrane-space protein system
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 624–635
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-protein metal and electron transfer experiments · source_derived_draft · unverified_draft
### copper-glutathione-cox17-recycling Glutathione reduced fully oxidized apo-COX17 back to the two-disulfide state in the protein-transfer system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione helps reset a mitochondrial copper courier. organism: Human proteins tissue_or_cell_type: Mitochondrial intermembrane-space protein system experimental_model: Purified-protein metal and electron transfer experiments limitations: Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly. exposure: Defined COX17 and SCO redox states; glutathione reduction evidence_span: {"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"} [copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
Complete structured claim and evidence
Ccs-null mice retained normal SOD1 protein abundance but had markedly reduced SOD1 copper incorporation and activity.
Mouse copper chaperone for SOD1 / Ccs → Mouse copper-zinc superoxide dismutase Sod1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/10694572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad", "start_char": 0, "end_char": 1205, "text_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad"}
experimental_model
Ccs knockout mice and radiocopper labeling
exposure
Ccs deletion
limitations
Normal protein abundance can coexist with low activity; the phenotype does not establish a general dietary copper deficiency.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Counting enzyme molecules alone misses whether the enzyme has its working metal.
primary_references
[copper-p10694572] Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. (2000). https://pubmed.ncbi.nlm.nih.gov/10694572/ DOI: 10.1073/pnas.040461197
tissue_or_cell_type
Multiple tissues and SOD1 protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 741–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ccs knockout mice and radiocopper labeling · source_derived_draft · unverified_draft
### copper-ccs-mouse-sod1 Ccs-null mice retained normal SOD1 protein abundance but had markedly reduced SOD1 copper incorporation and activity. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Counting enzyme molecules alone misses whether the enzyme has its working metal. organism: Mouse tissue_or_cell_type: Multiple tissues and SOD1 protein experimental_model: Ccs knockout mice and radiocopper labeling limitations: Normal protein abundance can coexist with low activity; the phenotype does not establish a general dietary copper deficiency. exposure: Ccs deletion evidence_span: {"source_cache": "artifacts/copper-research/10694572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad", "start_char": 0, "end_char": 1205, "text_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad"} [copper-p10694572] Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. (2000). https://pubmed.ncbi.nlm.nih.gov/10694572/ DOI: 10.1073/pnas.040461197
Complete structured claim and evidence
Human DBH is the copper-enzyme step converting dopamine to norepinephrine; the study resolved its catalytic-core architecture.
Human dopamine beta-hydroxylase / DBH → Norepinephrine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/27152332.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09", "start_char": 0, "end_char": 1325, "text_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09"}
experimental_model
Human DBH X-ray crystallography
exposure
Crystal structure at 2.9 angstrom resolution
limitations
Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein
plain_language
Copper is part of the enzyme that converts one neurotransmitter into another.
primary_references
[copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980
tissue_or_cell_type
Purified dimeric enzyme
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1079–1090
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DBH X-ray crystallography · source_derived_draft · unverified_draft
### copper-dbh-neurotransmitter-step Human DBH is the copper-enzyme step converting dopamine to norepinephrine; the study resolved its catalytic-core architecture. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper is part of the enzyme that converts one neurotransmitter into another. organism: Human protein tissue_or_cell_type: Purified dimeric enzyme experimental_model: Human DBH X-ray crystallography limitations: Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake. exposure: Crystal structure at 2.9 angstrom resolution evidence_span: {"source_cache": "artifacts/copper-research/27152332.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09", "start_char": 0, "end_char": 1325, "text_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09"} [copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980
Complete structured claim and evidence
Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites.
Human diamine oxidase / AOC1 / DAO → Protein-derived topaquinone / TPQ cofactor source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/19764817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6", "start_char": 0, "end_char": 1343, "text_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6"}
experimental_model
Crystallography of recombinant human diamine oxidase and inhibitor complexes
exposure
Native structure and inhibitor binding
limitations
Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human AOC1 expressed in insect cells
plain_language
Histamine-processing machinery includes both a metal and a protein-derived cofactor.
primary_references
[copper-p19764817] Structure and inhibition of human diamine oxidase. (2009). https://pubmed.ncbi.nlm.nih.gov/19764817/ DOI: 10.1021/bi9014192
tissue_or_cell_type
Purified protein
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1014–1025
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography of recombinant human diamine oxidase and inhibitor complexes · source_derived_draft · unverified_draft
### copper-aoc1-copper-tpq Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Histamine-processing machinery includes both a metal and a protein-derived cofactor. organism: Human AOC1 expressed in insect cells tissue_or_cell_type: Purified protein experimental_model: Crystallography of recombinant human diamine oxidase and inhibitor complexes limitations: Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants. exposure: Native structure and inhibitor binding evidence_span: {"source_cache": "artifacts/copper-research/19764817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6", "start_char": 0, "end_char": 1343, "text_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6"} [copper-p19764817] Structure and inhibition of human diamine oxidase. (2009). https://pubmed.ncbi.nlm.nih.gov/19764817/ DOI: 10.1021/bi9014192
Complete structured claim and evidence
CTR1-mediated radiocopper transport was energy independent and increased at acidic extracellular pH and high extracellular potassium in the assay.
Human high-affinity copper transporter CTR1 / SLC31A1 → Cellular copper uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/11734551.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c", "start_char": 0, "end_char": 1144, "text_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c"}
experimental_model
Human CTR1 expression and radiocopper transport assays
exposure
CTR1 expression; pH and potassium changes in culture
limitations
Transport kinetics in cells; elevated assay potassium is not evidence that potassium supplements improve human copper status.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein in human HEK293 cells
plain_language
The chemical surroundings changed transport speed; this is not a dietary potassium recommendation.
primary_references
[copper-p11734551] Biochemical characterization of the human copper transporter Ctr1. (2002). https://pubmed.ncbi.nlm.nih.gov/11734551/ DOI: 10.1074/jbc.m104728200
tissue_or_cell_type
Plasma membrane
transport_effect
raises The object already names cellular copper uptake.
transport_pool
the cytosol The object already names cellular copper uptake.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 260–271
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CTR1 expression and radiocopper transport assays · source_derived_draft · unverified_draft
### copper-ctr1-energy-ph CTR1-mediated radiocopper transport was energy independent and increased at acidic extracellular pH and high extracellular potassium in the assay. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The chemical surroundings changed transport speed; this is not a dietary potassium recommendation. organism: Human protein in human HEK293 cells tissue_or_cell_type: Plasma membrane experimental_model: Human CTR1 expression and radiocopper transport assays limitations: Transport kinetics in cells; elevated assay potassium is not evidence that potassium supplements improve human copper status. exposure: CTR1 expression; pH and potassium changes in culture evidence_span: {"source_cache": "artifacts/copper-research/11734551.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c", "start_char": 0, "end_char": 1144, "text_sha256": "e7b07ef7169b07bef414cdfb8996cffda2636f9a1bcd93b556d22bdce980a03c"} [copper-p11734551] Biochemical characterization of the human copper transporter Ctr1. (2002). https://pubmed.ncbi.nlm.nih.gov/11734551/ DOI: 10.1074/jbc.m104728200
Complete structured claim and evidence
Expressed mouse Steap2 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system.
Mouse metalloreductase Steap2 → Copper(II) ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/16609065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f", "start_char": 0, "end_char": 827, "text_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f"}
experimental_model
Mouse Steap expression constructs and metal-reduction assays
exposure
Transient expression of Steap2, Steap3 or Steap4
limitations
Protein species verified in primary Methods (PMC1785011). Overexpression does not establish the dominant intestinal reductase in humans; relative activity can reflect localization and abundance.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse proteins expressed in human HEK293T cells
plain_language
This enzyme prepares copper in a chemical form compatible with uptake.
primary_references
[copper-p16609065] The Steap proteins are metalloreductases. (2006). https://pubmed.ncbi.nlm.nih.gov/16609065/ DOI: 10.1182/blood-2006-02-003681
tissue_or_cell_type
Cell surface and endosomal compartments
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 273–284
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse Steap expression constructs and metal-reduction assays · source_derived_draft · unverified_draft
### copper-steap2-reduces-copper Expressed mouse Steap2 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme prepares copper in a chemical form compatible with uptake. organism: Mouse proteins expressed in human HEK293T cells tissue_or_cell_type: Cell surface and endosomal compartments experimental_model: Mouse Steap expression constructs and metal-reduction assays limitations: Protein species verified in primary Methods (PMC1785011). Overexpression does not establish the dominant intestinal reductase in humans; relative activity can reflect localization and abundance. exposure: Transient expression of Steap2, Steap3 or Steap4 evidence_span: {"source_cache": "artifacts/copper-research/16609065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f", "start_char": 0, "end_char": 827, "text_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f"} [copper-p16609065] The Steap proteins are metalloreductases. (2006). https://pubmed.ncbi.nlm.nih.gov/16609065/ DOI: 10.1182/blood-2006-02-003681
Complete structured claim and evidence
Expressed mouse Steap3 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system.
Mouse metalloreductase Steap3 → Copper(II) ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/16609065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f", "start_char": 0, "end_char": 827, "text_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f"}
experimental_model
Mouse Steap expression constructs and metal-reduction assays
exposure
Transient expression of Steap2, Steap3 or Steap4
limitations
Protein species verified in primary Methods (PMC1785011). Overexpression does not establish the dominant intestinal reductase in humans; relative activity can reflect localization and abundance.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse proteins expressed in human HEK293T cells
plain_language
This enzyme prepares copper in a chemical form compatible with uptake.
primary_references
[copper-p16609065] The Steap proteins are metalloreductases. (2006). https://pubmed.ncbi.nlm.nih.gov/16609065/ DOI: 10.1182/blood-2006-02-003681
tissue_or_cell_type
Cell surface and endosomal compartments
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 286–297
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse Steap expression constructs and metal-reduction assays · source_derived_draft · unverified_draft
### copper-steap3-reduces-copper Expressed mouse Steap3 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme prepares copper in a chemical form compatible with uptake. organism: Mouse proteins expressed in human HEK293T cells tissue_or_cell_type: Cell surface and endosomal compartments experimental_model: Mouse Steap expression constructs and metal-reduction assays limitations: Protein species verified in primary Methods (PMC1785011). Overexpression does not establish the dominant intestinal reductase in humans; relative activity can reflect localization and abundance. exposure: Transient expression of Steap2, Steap3 or Steap4 evidence_span: {"source_cache": "artifacts/copper-research/16609065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f", "start_char": 0, "end_char": 827, "text_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f"} [copper-p16609065] The Steap proteins are metalloreductases. (2006). https://pubmed.ncbi.nlm.nih.gov/16609065/ DOI: 10.1182/blood-2006-02-003681
Complete structured claim and evidence
Expressed mouse Steap4 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system.
Mouse metalloreductase Steap4 → Copper(II) ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/16609065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f", "start_char": 0, "end_char": 827, "text_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f"}
experimental_model
Mouse Steap expression constructs and metal-reduction assays
exposure
Transient expression of Steap2, Steap3 or Steap4
limitations
Protein species verified in primary Methods (PMC1785011). Overexpression does not establish the dominant intestinal reductase in humans; relative activity can reflect localization and abundance.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse proteins expressed in human HEK293T cells
plain_language
This enzyme prepares copper in a chemical form compatible with uptake.
primary_references
[copper-p16609065] The Steap proteins are metalloreductases. (2006). https://pubmed.ncbi.nlm.nih.gov/16609065/ DOI: 10.1182/blood-2006-02-003681
tissue_or_cell_type
Cell surface and endosomal compartments
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 299–310
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse Steap expression constructs and metal-reduction assays · source_derived_draft · unverified_draft
### copper-steap4-reduces-copper Expressed mouse Steap4 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme prepares copper in a chemical form compatible with uptake. organism: Mouse proteins expressed in human HEK293T cells tissue_or_cell_type: Cell surface and endosomal compartments experimental_model: Mouse Steap expression constructs and metal-reduction assays limitations: Protein species verified in primary Methods (PMC1785011). Overexpression does not establish the dominant intestinal reductase in humans; relative activity can reflect localization and abundance. exposure: Transient expression of Steap2, Steap3 or Steap4 evidence_span: {"source_cache": "artifacts/copper-research/16609065.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f", "start_char": 0, "end_char": 827, "text_sha256": "d0f42a3f30c22ba4235d82f21ba165c78b6c519a6218f487411fb2247ecc0d9f"} [copper-p16609065] The Steap proteins are metalloreductases. (2006). https://pubmed.ncbi.nlm.nih.gov/16609065/ DOI: 10.1182/blood-2006-02-003681
Complete structured claim and evidence
Intestinal Ctr1 deletion reduced peripheral copper availability and caused neonatal growth failure and cardiac hypertrophy in mice.
Mouse copper transporter Ctr1 / Slc31a1 → Delivery of intestinal copper to peripheral tissues source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"}
experimental_model
Intestinal epithelial Ctr1 knockout mice
exposure
Intestinal Ctr1 deletion; postnatal copper rescue
limitations
Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Copper in food is not enough if the intestine cannot deliver it to the body.
primary_references
[copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009
tissue_or_cell_type
Intestine and peripheral organs
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 312–323
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal epithelial Ctr1 knockout mice · source_derived_draft · unverified_draft
### copper-intestinal-ctr1-systemic Intestinal Ctr1 deletion reduced peripheral copper availability and caused neonatal growth failure and cardiac hypertrophy in mice. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper in food is not enough if the intestine cannot deliver it to the body. organism: Mouse tissue_or_cell_type: Intestine and peripheral organs experimental_model: Intestinal epithelial Ctr1 knockout mice limitations: Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose. exposure: Intestinal Ctr1 deletion; postnatal copper rescue evidence_span: {"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"} [copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009
Complete structured claim and evidence
Mice lacking intestinal Ctr1 developed hepatic iron overload alongside systemic copper deficiency.
Mouse copper transporter Ctr1 / Slc31a1 → Mouse hepatic iron accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"}
experimental_model
Intestinal epithelial Ctr1 knockout mice
exposure
Intestinal Ctr1 deletion; postnatal copper rescue
limitations
Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
A copper transport defect also disrupted where iron accumulated.
primary_references
[copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009
tissue_or_cell_type
Intestine and peripheral organs
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 325–336
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal epithelial Ctr1 knockout mice · source_derived_draft · unverified_draft
### copper-intestinal-ctr1-iron Mice lacking intestinal Ctr1 developed hepatic iron overload alongside systemic copper deficiency. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper transport defect also disrupted where iron accumulated. organism: Mouse tissue_or_cell_type: Intestine and peripheral organs experimental_model: Intestinal epithelial Ctr1 knockout mice limitations: Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose. exposure: Intestinal Ctr1 deletion; postnatal copper rescue evidence_span: {"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"} [copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009
Complete structured claim and evidence
A single postnatal copper administration partially rescued growth and viability in intestinal Ctr1 knockout mice.
Copper → Delivery of intestinal copper to peripheral tissues source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"}
experimental_model
Intestinal epithelial Ctr1 knockout mice
exposure
Intestinal Ctr1 deletion; postnatal copper rescue
limitations
Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Some consequences of the transport defect could be bypassed in this animal experiment.
primary_references
[copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009
tissue_or_cell_type
Intestine and peripheral organs
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 338–349
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal epithelial Ctr1 knockout mice · source_derived_draft · unverified_draft
### copper-intestinal-ctr1-copper-rescue A single postnatal copper administration partially rescued growth and viability in intestinal Ctr1 knockout mice. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some consequences of the transport defect could be bypassed in this animal experiment. organism: Mouse tissue_or_cell_type: Intestine and peripheral organs experimental_model: Intestinal epithelial Ctr1 knockout mice limitations: Genetic intestinal transport failure differs from low dietary intake. The indexed abstract does not establish the administration route of the rescue dose. exposure: Intestinal Ctr1 deletion; postnatal copper rescue evidence_span: {"source_cache": "artifacts/copper-research/16950140.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98", "start_char": 0, "end_char": 1026, "text_sha256": "08532f69fd9530033f8d9afcece9249fc50dd425f57313e120f55ea81cee8f98"} [copper-p16950140] Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function. (2006). https://pubmed.ncbi.nlm.nih.gov/16950140/ DOI: 10.1016/j.cmet.2006.08.009
Complete structured claim and evidence
Dietary copper limitation increased total and apically localized Ctr1 protein in mouse intestine.
Copper → Mouse intestinal apical Ctr1 protein abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/20699218.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c638594d4e707bb39a8f2e8c1fed15a42982e1dc4d525fda112d28281a853012", "start_char": 0, "end_char": 1749, "text_sha256": "c638594d4e707bb39a8f2e8c1fed15a42982e1dc4d525fda112d28281a853012"}
experimental_model
Intestinal immunolocalization and dietary copper limitation
exposure
Copper limitation in mice
limitations
Apical Ctr1 was observed in the examined mammalian preparations; membrane localization is model dependent and cannot be assigned universally to every human intestinal condition.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse, rat and pig; human HEK293T cells for separate processing experiments
plain_language
The intestine increased an entry route when copper supply fell.
primary_references
[copper-p20699218] Ctr1 is an apical copper transporter in mammalian intestinal epithelial cells in vivo that is controlled at the level of protein stability. (2010). https://pubmed.ncbi.nlm.nih.gov/20699218/ DOI: 10.1074/jbc.m110.143826
tissue_or_cell_type
Intestinal epithelium
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 351–362
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestinal immunolocalization and dietary copper limitation · source_derived_draft · unverified_draft
### copper-ctr1-intestinal-adaptation Dietary copper limitation increased total and apically localized Ctr1 protein in mouse intestine. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intestine increased an entry route when copper supply fell. organism: Mouse, rat and pig; human HEK293T cells for separate processing experiments tissue_or_cell_type: Intestinal epithelium experimental_model: Intestinal immunolocalization and dietary copper limitation limitations: Apical Ctr1 was observed in the examined mammalian preparations; membrane localization is model dependent and cannot be assigned universally to every human intestinal condition. exposure: Copper limitation in mice evidence_span: {"source_cache": "artifacts/copper-research/20699218.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c638594d4e707bb39a8f2e8c1fed15a42982e1dc4d525fda112d28281a853012", "start_char": 0, "end_char": 1749, "text_sha256": "c638594d4e707bb39a8f2e8c1fed15a42982e1dc4d525fda112d28281a853012"} [copper-p20699218] Ctr1 is an apical copper transporter in mammalian intestinal epithelial cells in vivo that is controlled at the level of protein stability. (2010). https://pubmed.ncbi.nlm.nih.gov/20699218/ DOI: 10.1074/jbc.m110.143826
Complete structured claim and evidence
Atox1-deficient fibroblasts accumulated copper because cellular copper efflux was reduced.
Mouse copper chaperone Atox1 → Cellular copper efflux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/12538877.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283", "start_char": 0, "end_char": 1579, "text_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283"}
experimental_model
Atox1-null and control immortalized embryonic fibroblasts
exposure
Atox1 deletion and copper challenge
limitations
Trafficking and efflux are related but distinguishable; this is a cell knockout study, not human dietary depletion.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Copper can build up while its delivery and removal machinery works poorly.
primary_references
[copper-p12538877] Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. (2003). https://pubmed.ncbi.nlm.nih.gov/12538877/ DOI: 10.1073/pnas.0336230100
tissue_or_cell_type
Fibroblast Golgi and cellular copper pools
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 364–375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atox1-null and control immortalized embryonic fibroblasts · source_derived_draft · unverified_draft
### copper-atox1-efflux Atox1-deficient fibroblasts accumulated copper because cellular copper efflux was reduced. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper can build up while its delivery and removal machinery works poorly. organism: Mouse tissue_or_cell_type: Fibroblast Golgi and cellular copper pools experimental_model: Atox1-null and control immortalized embryonic fibroblasts limitations: Trafficking and efflux are related but distinguishable; this is a cell knockout study, not human dietary depletion. exposure: Atox1 deletion and copper challenge evidence_span: {"source_cache": "artifacts/copper-research/12538877.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283", "start_char": 0, "end_char": 1579, "text_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283"} [copper-p12538877] Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. (2003). https://pubmed.ncbi.nlm.nih.gov/12538877/ DOI: 10.1073/pnas.0336230100
Complete structured claim and evidence
Atox1 loss impaired copper-responsive ATP7A movement from the Golgi even when intracellular copper concentrations were matched.
Mouse copper chaperone Atox1 → Copper-responsive ATP7A exit from the Golgi source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/12538877.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283", "start_char": 0, "end_char": 1579, "text_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283"}
experimental_model
Atox1-null and control immortalized embryonic fibroblasts
exposure
Atox1 deletion and copper challenge
limitations
Trafficking and efflux are related but distinguishable; this is a cell knockout study, not human dietary depletion.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The copper courier affects transporter behavior as well as total copper content.
primary_references
[copper-p12538877] Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. (2003). https://pubmed.ncbi.nlm.nih.gov/12538877/ DOI: 10.1073/pnas.0336230100
tissue_or_cell_type
Fibroblast Golgi and cellular copper pools
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 377–388
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atox1-null and control immortalized embryonic fibroblasts · source_derived_draft · unverified_draft
### copper-atox1-atp7a-traffic Atox1 loss impaired copper-responsive ATP7A movement from the Golgi even when intracellular copper concentrations were matched. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper courier affects transporter behavior as well as total copper content. organism: Mouse tissue_or_cell_type: Fibroblast Golgi and cellular copper pools experimental_model: Atox1-null and control immortalized embryonic fibroblasts limitations: Trafficking and efflux are related but distinguishable; this is a cell knockout study, not human dietary depletion. exposure: Atox1 deletion and copper challenge evidence_span: {"source_cache": "artifacts/copper-research/12538877.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283", "start_char": 0, "end_char": 1579, "text_sha256": "480f54240ace7abfb1e0a00ae4f113de3bb518ae356fc523354ced9619428283"} [copper-p12538877] Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase. (2003). https://pubmed.ncbi.nlm.nih.gov/12538877/ DOI: 10.1073/pnas.0336230100
Complete structured claim and evidence
Copper transfer from ATOX1 reduced interactions within ATP7B MBD1-3 and increased domain mobility.
Human copper chaperone ATOX1 → ATP7B N-terminal metal-binding domain mobility source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/28900031.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8", "start_char": 0, "end_char": 1471, "text_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8"}
experimental_model
Biochemistry, solution NMR and small-angle X-ray scattering
exposure
Apo versus copper-loaded ATOX1
limitations
Domain motion and ATP hydrolysis were studied directly; these assays do not establish a whole-body copper requirement.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human proteins
plain_language
Copper handoff changes how the pump can move.
primary_references
[copper-p28900031] The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics. (2017). https://pubmed.ncbi.nlm.nih.gov/28900031/ DOI: 10.1074/jbc.m117.811752
tissue_or_cell_type
Purified ATOX1 and ATP7B domains
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 403–414
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemistry, solution NMR and small-angle X-ray scattering · source_derived_draft · unverified_draft
### copper-atox1-atp7b-mobility Copper transfer from ATOX1 reduced interactions within ATP7B MBD1-3 and increased domain mobility. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper handoff changes how the pump can move. organism: Human proteins tissue_or_cell_type: Purified ATOX1 and ATP7B domains experimental_model: Biochemistry, solution NMR and small-angle X-ray scattering limitations: Domain motion and ATP hydrolysis were studied directly; these assays do not establish a whole-body copper requirement. exposure: Apo versus copper-loaded ATOX1 evidence_span: {"source_cache": "artifacts/copper-research/28900031.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8", "start_char": 0, "end_char": 1471, "text_sha256": "64fceb98b5bf2ca406f26799cea5832b0306883118b9ad2416ba87db47b18ce8"} [copper-p28900031] The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics. (2017). https://pubmed.ncbi.nlm.nih.gov/28900031/ DOI: 10.1074/jbc.m117.811752
Complete structured claim and evidence
Elevated copper redirected ATP7B from the trans-Golgi network to a subset of lysosomes.
Human copper-transporting ATPase ATP7B → ATP7B trafficking from Golgi to lysosomes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"}
experimental_model
Copper perturbation, imaging and trafficking assays in hepatocyte systems
exposure
Copper challenge and lysosomal exocytosis perturbation
limitations
The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human HepG2 cells with complementary hepatic models
plain_language
The liver-cell copper pump changes location when copper rises.
primary_references
[copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
tissue_or_cell_type
Golgi, lysosomes and canalicular pole
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 416–427
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper perturbation, imaging and trafficking assays in hepatocyte systems · source_derived_draft · unverified_draft
### copper-atp7b-lysosomes Elevated copper redirected ATP7B from the trans-Golgi network to a subset of lysosomes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver-cell copper pump changes location when copper rises. organism: Human HepG2 cells with complementary hepatic models tissue_or_cell_type: Golgi, lysosomes and canalicular pole experimental_model: Copper perturbation, imaging and trafficking assays in hepatocyte systems limitations: The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62. exposure: Copper challenge and lysosomal exocytosis perturbation evidence_span: {"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"} [copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
Complete structured claim and evidence
Lysosomal ATP7B transported copper into the lysosomal lumen.
Human copper-transporting ATPase ATP7B → Copper accumulation in the lysosomal lumen source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"}
experimental_model
Copper perturbation, imaging and trafficking assays in hepatocyte systems
exposure
Copper challenge and lysosomal exocytosis perturbation
limitations
The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human HepG2 cells with complementary hepatic models
plain_language
A temporary storage compartment helps prepare copper for removal.
primary_references
[copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
tissue_or_cell_type
Golgi, lysosomes and canalicular pole
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 429–440
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper perturbation, imaging and trafficking assays in hepatocyte systems · source_derived_draft · unverified_draft
### copper-atp7b-lysosomal-loading Lysosomal ATP7B transported copper into the lysosomal lumen. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A temporary storage compartment helps prepare copper for removal. organism: Human HepG2 cells with complementary hepatic models tissue_or_cell_type: Golgi, lysosomes and canalicular pole experimental_model: Copper perturbation, imaging and trafficking assays in hepatocyte systems limitations: The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62. exposure: Copper challenge and lysosomal exocytosis perturbation evidence_span: {"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"} [copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
Complete structured claim and evidence
ATP7B interaction with dynactin p62 supported movement of copper-containing lysosomes toward the hepatocyte canalicular pole.
Human copper-transporting ATPase ATP7B → Human dynactin subunit 4 / DCTN4 / dynactin p62 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"}
experimental_model
Copper perturbation, imaging and trafficking assays in hepatocyte systems
exposure
Copper challenge and lysosomal exocytosis perturbation
limitations
The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human HepG2 cells with complementary hepatic models
plain_language
Transporter placement helps route copper toward bile.
primary_references
[copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
tissue_or_cell_type
Golgi, lysosomes and canalicular pole
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 442–453
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper perturbation, imaging and trafficking assays in hepatocyte systems · source_derived_draft · unverified_draft
### copper-atp7b-dynactin ATP7B interaction with dynactin p62 supported movement of copper-containing lysosomes toward the hepatocyte canalicular pole. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Transporter placement helps route copper toward bile. organism: Human HepG2 cells with complementary hepatic models tissue_or_cell_type: Golgi, lysosomes and canalicular pole experimental_model: Copper perturbation, imaging and trafficking assays in hepatocyte systems limitations: The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62. exposure: Copper challenge and lysosomal exocytosis perturbation evidence_span: {"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"} [copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
Complete structured claim and evidence
Stimulating lysosomal exocytosis increased ATP7B delivery toward the canalicular membrane and copper release into the biliary space.
Lysosomal exocytosis at the hepatocyte canalicular pole → Copper excretion toward bile source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"}
experimental_model
Copper perturbation, imaging and trafficking assays in hepatocyte systems
exposure
Copper challenge and lysosomal exocytosis perturbation
limitations
The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human HepG2 cells with complementary hepatic models
plain_language
Lysosome fusion provides a route out of the liver cell for excess copper.
primary_references
[copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
tissue_or_cell_type
Golgi, lysosomes and canalicular pole
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 455–466
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper perturbation, imaging and trafficking assays in hepatocyte systems · source_derived_draft · unverified_draft
### copper-lysosome-bile-export Stimulating lysosomal exocytosis increased ATP7B delivery toward the canalicular membrane and copper release into the biliary space. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lysosome fusion provides a route out of the liver cell for excess copper. organism: Human HepG2 cells with complementary hepatic models tissue_or_cell_type: Golgi, lysosomes and canalicular pole experimental_model: Copper perturbation, imaging and trafficking assays in hepatocyte systems limitations: The main cellular trafficking observations are mechanistic; experimental copper exposures and mutant rescue do not establish a clinical treatment. Dynactin p62 is DCTN4, not autophagy SQSTM1/p62. exposure: Copper challenge and lysosomal exocytosis perturbation evidence_span: {"source_cache": "artifacts/copper-research/24909901.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b", "start_char": 0, "end_char": 1036, "text_sha256": "abfdc86e4b47b489037af635672033532c905d291127030d9dbcfc02e998c20b"} [copper-p24909901] Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24909901/ DOI: 10.1016/j.devcel.2014.04.033
Complete structured claim and evidence
Ctr2 was required for normal formation of the ectodomain-cleaved form of Ctr1 in mice.
Mouse copper transporter Ctr2 / Slc31a2 → Mouse Ctr1 with cleaved extracellular N-terminal domain source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/24167251.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968", "start_char": 0, "end_char": 1212, "text_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968"}
experimental_model
Ctr2 knockout and Ctr1 processing experiments
exposure
Ctr2 deletion
limitations
CTR2 regulates truncated CTR1 and intracellular mobilization; it should not simply be treated as a duplicate plasma-membrane CTR1 importer.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
One copper transporter controls the processing of another.
primary_references
[copper-p24167251] Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain. (2013). https://pubmed.ncbi.nlm.nih.gov/24167251/ DOI: 10.1073/pnas.1311749110
tissue_or_cell_type
Tissues and endosomal copper pools
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 468–479
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ctr2 knockout and Ctr1 processing experiments · source_derived_draft · unverified_draft
### copper-ctr2-ctr1-cleavage Ctr2 was required for normal formation of the ectodomain-cleaved form of Ctr1 in mice. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: One copper transporter controls the processing of another. organism: Mouse tissue_or_cell_type: Tissues and endosomal copper pools experimental_model: Ctr2 knockout and Ctr1 processing experiments limitations: CTR2 regulates truncated CTR1 and intracellular mobilization; it should not simply be treated as a duplicate plasma-membrane CTR1 importer. exposure: Ctr2 deletion evidence_span: {"source_cache": "artifacts/copper-research/24167251.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968", "start_char": 0, "end_char": 1212, "text_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968"} [copper-p24167251] Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain. (2013). https://pubmed.ncbi.nlm.nih.gov/24167251/ DOI: 10.1073/pnas.1311749110
Complete structured claim and evidence
The truncated Ctr1 form mobilized endosomal copper stores, whereas full-length Ctr1 efficiently supported plasma-membrane uptake.
Mouse Ctr1 with cleaved extracellular N-terminal domain → Mobilization of copper from endosomal stores source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/24167251.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968", "start_char": 0, "end_char": 1212, "text_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968"}
experimental_model
Ctr2 knockout and Ctr1 processing experiments
exposure
Ctr2 deletion
limitations
CTR2 regulates truncated CTR1 and intracellular mobilization; it should not simply be treated as a duplicate plasma-membrane CTR1 importer.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Copper trapped inside a compartment needs a different access step.
primary_references
[copper-p24167251] Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain. (2013). https://pubmed.ncbi.nlm.nih.gov/24167251/ DOI: 10.1073/pnas.1311749110
tissue_or_cell_type
Endosomal stores versus plasma-membrane uptake
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 481–492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ctr2 knockout and Ctr1 processing experiments · source_derived_draft · unverified_draft
### copper-truncated-ctr1-endosome The truncated Ctr1 form mobilized endosomal copper stores, whereas full-length Ctr1 efficiently supported plasma-membrane uptake. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper trapped inside a compartment needs a different access step. organism: Mouse tissue_or_cell_type: Endosomal stores versus plasma-membrane uptake experimental_model: Ctr2 knockout and Ctr1 processing experiments limitations: CTR2 regulates truncated CTR1 and intracellular mobilization; it should not simply be treated as a duplicate plasma-membrane CTR1 importer. exposure: Ctr2 deletion evidence_span: {"source_cache": "artifacts/copper-research/24167251.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968", "start_char": 0, "end_char": 1212, "text_sha256": "7315e9041dddd5510d6efd970560c80316d38120ba1d8eefca10952be8ea0968"} [copper-p24167251] Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain. (2013). https://pubmed.ncbi.nlm.nih.gov/24167251/ DOI: 10.1073/pnas.1311749110
Complete structured claim and evidence
Copper deficiency lowered ATP7A abundance in mouse peripheral tissues; subcutaneous copper restored it.
Copper → Mouse peripheral-tissue ATP7A abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"}
experimental_model
Copper-deficient mouse models and subcutaneous copper administration
exposure
Systemic copper depletion and restoration
limitations
Opposite tissue responses are reported regulatory context, not a contradiction in the source.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Tissues adjusted their copper-export machinery as supply changed.
primary_references
[copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z
tissue_or_cell_type
Intestine, heart, spleen and liver
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 494–505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper-deficient mouse models and subcutaneous copper administration · source_derived_draft · unverified_draft
### copper-atp7a-peripheral-response Copper deficiency lowered ATP7A abundance in mouse peripheral tissues; subcutaneous copper restored it. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Tissues adjusted their copper-export machinery as supply changed. organism: Mouse tissue_or_cell_type: Intestine, heart, spleen and liver experimental_model: Copper-deficient mouse models and subcutaneous copper administration limitations: Opposite tissue responses are reported regulatory context, not a contradiction in the source. exposure: Systemic copper depletion and restoration evidence_span: {"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"} [copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z
Complete structured claim and evidence
Low systemic copper increased intestinal ATP7A, while subcutaneous copper lowered it in the same mouse study.
Copper → Mouse intestinal ATP7A abundance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"}
experimental_model
Copper-deficient mouse models and subcutaneous copper administration
exposure
Systemic copper depletion and restoration
limitations
Opposite tissue responses are reported regulatory context, not a contradiction in the source.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The intestine responded in the opposite direction, consistent with delivering copper to the rest of the body.
primary_references
[copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z
tissue_or_cell_type
Intestine, heart, spleen and liver
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 507–518
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper-deficient mouse models and subcutaneous copper administration · source_derived_draft · unverified_draft
### copper-atp7a-intestinal-response Low systemic copper increased intestinal ATP7A, while subcutaneous copper lowered it in the same mouse study. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intestine responded in the opposite direction, consistent with delivering copper to the rest of the body. organism: Mouse tissue_or_cell_type: Intestine, heart, spleen and liver experimental_model: Copper-deficient mouse models and subcutaneous copper administration limitations: Opposite tissue responses are reported regulatory context, not a contradiction in the source. exposure: Systemic copper depletion and restoration evidence_span: {"source_cache": "artifacts/copper-research/28931909.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f", "start_char": 0, "end_char": 1284, "text_sha256": "040f84f61342770e57eec0c3e82a0165c000bc5592a54344f92378b48e626c9f"} [copper-p28931909] Organ-specific regulation of ATP7A abundance is coordinated with systemic copper homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28931909/ DOI: 10.1038/s41598-017-11961-z
Complete structured claim and evidence
SLC25A3 supported copper transport in heterologous assays and reconstituted liposomes.
Human mitochondrial phosphate/copper carrier SLC25A3 → Copper source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"}
experimental_model
Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes
exposure
SLC25A3 loss or reconstitution; extracellular copper addition
limitations
The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human and mouse cells; heterologous yeast and Lactococcus assays
plain_language
The mitochondrial phosphate carrier also moves copper.
primary_references
[copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
tissue_or_cell_type
Inner mitochondrial membrane
transport_effect
depends Transport supported in heterologous assays and liposomes, with no direction recorded.
transport_pool
the mitochondrial matrix Transport supported in heterologous assays and liposomes, with no direction recorded.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 520–531
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes · source_derived_draft · unverified_draft
### copper-slc25a3-copper-carrier SLC25A3 supported copper transport in heterologous assays and reconstituted liposomes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial phosphate carrier also moves copper. organism: Human and mouse cells; heterologous yeast and Lactococcus assays tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes limitations: The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments. exposure: SLC25A3 loss or reconstitution; extracellular copper addition evidence_span: {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"} [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
Complete structured claim and evidence
SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study.
Human mitochondrial phosphate/copper carrier SLC25A3 → Mitochondrial cytochrome c oxidase / respiratory complex IV source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"}
experimental_model
Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes
exposure
SLC25A3 loss or reconstitution; extracellular copper addition
limitations
The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human and mouse cells; heterologous yeast and Lactococcus assays
plain_language
Getting enough copper to the respiratory enzyme depends on transport machinery.
primary_references
[copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
tissue_or_cell_type
Inner mitochondrial membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 533–544
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes · source_derived_draft · unverified_draft
### copper-slc25a3-cox-deficiency SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Getting enough copper to the respiratory enzyme depends on transport machinery. organism: Human and mouse cells; heterologous yeast and Lactococcus assays tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes limitations: The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments. exposure: SLC25A3 loss or reconstitution; extracellular copper addition evidence_span: {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"} [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
Complete structured claim and evidence
Human SLC25A3 expression increased copper export from copper-loaded Lactococcus lactis, supporting an export function.
Human mitochondrial phosphate/copper carrier SLC25A3 → Copper export across the mitochondrial inner membrane toward the intermembrane space source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"}
experimental_model
Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria
exposure
Slc25a3 deletion and elesclomol-copper exposure
limitations
Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein in Lactococcus lactis
plain_language
The carrier can move copper outward as well as support its entry.
primary_references
[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
tissue_or_cell_type
Bacterial assay; mitochondrial export is the linked interpretation
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 546–557
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft
### copper-slc25a3-export Human SLC25A3 expression increased copper export from copper-loaded Lactococcus lactis, supporting an export function. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier can move copper outward as well as support its entry. organism: Human protein in Lactococcus lactis tissue_or_cell_type: Bacterial assay; mitochondrial export is the linked interpretation experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92", "start_char": 0, "end_char": 1276, "text_sha256": "a172ec9e3d13811a6e6a745d2017398361cc01ec2a06c65065b82ffd06d26d92"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
Complete structured claim and evidence
Slc25a3-null rat cells exposed to elesclomol-copper showed increased DLAT oligomerization and loss of lipoylated DLAT and DLST.
Elesclomol-copper complex → Rat lipoylated Dlat oligomerization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 5507, "end_char": 5866, "text_sha256": "77f0d121a0aed5bdcd3c4898c369533a29208ebd8a9450a3a37ceff5d783c3af"}
experimental_model
Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria
exposure
Slc25a3 deletion and elesclomol-copper exposure
limitations
Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat H9c2 cells; human SLC25A3 in Lactococcus lactis
plain_language
Misplaced copper damaged proteins that normally carry lipoamide.
primary_references
[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
tissue_or_cell_type
Mitochondria; bacterial copper export assay
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 572–583
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft
### copper-slc25a3-es-dlat Slc25a3-null rat cells exposed to elesclomol-copper showed increased DLAT oligomerization and loss of lipoylated DLAT and DLST. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Misplaced copper damaged proteins that normally carry lipoamide. organism: Rat H9c2 cells; human SLC25A3 in Lactococcus lactis tissue_or_cell_type: Mitochondria; bacterial copper export assay experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 5507, "end_char": 5866, "text_sha256": "77f0d121a0aed5bdcd3c4898c369533a29208ebd8a9450a3a37ceff5d783c3af"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
Complete structured claim and evidence
Elesclomol-copper reduced the iron-sulfur proteins SDHB and ACO2 in Slc25a3-null rat cells.
Elesclomol-copper complex → Rat succinate dehydrogenase iron-sulfur subunit Sdhb source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 4157, "end_char": 4553, "text_sha256": "458c46d27cddab000b77009e2f8f1d373871eaa90d0571867d421984ecd9803a"}
experimental_model
Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria
exposure
Slc25a3 deletion and elesclomol-copper exposure
limitations
Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat H9c2 cells; human SLC25A3 in Lactococcus lactis
plain_language
Copper misrouting also affected enzymes that depend on iron-sulfur clusters.
primary_references
[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
tissue_or_cell_type
Mitochondria; bacterial copper export assay
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 585–596
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft
### copper-slc25a3-es-fe-s Elesclomol-copper reduced the iron-sulfur proteins SDHB and ACO2 in Slc25a3-null rat cells. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper misrouting also affected enzymes that depend on iron-sulfur clusters. organism: Rat H9c2 cells; human SLC25A3 in Lactococcus lactis tissue_or_cell_type: Mitochondria; bacterial copper export assay experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 4157, "end_char": 4553, "text_sha256": "458c46d27cddab000b77009e2f8f1d373871eaa90d0571867d421984ecd9803a"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123
Complete structured claim and evidence
Oral elesclomol without extra copper supplementation rescued neonatal mortality in intestine-specific Ctr1 knockout mice.
Elesclomol → Delivery of intestinal copper to peripheral tissues source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/35433682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ebf1fdc967be53f455383e4edc79468266a5685db3867ca04ce2e2ccc4f2617", "start_char": 0, "end_char": 1449, "text_sha256": "6ebf1fdc967be53f455383e4edc79468266a5685db3867ca04ce2e2ccc4f2617"}
experimental_model
Oral elesclomol in genetically copper-transport-defective animals
exposure
Oral drug exposure without additional copper supplementation
limitations
Animal rescue does not establish safety or efficacy in people. Intestinal CTR1 loss is a different block from mitochondrial SLC25A3 loss.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse; separate Caenorhabditis elegans experiments
plain_language
The drug helped use existing dietary copper despite a missing intestinal entry route.
primary_references
[copper-p35433682] Oral Elesclomol Treatment Alleviates Copper Deficiency in Animal Models. (2022). https://pubmed.ncbi.nlm.nih.gov/35433682/ DOI: 10.3389/fcell.2022.856300
tissue_or_cell_type
Intestine and whole-animal development
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 598–609
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral elesclomol in genetically copper-transport-defective animals · source_derived_draft · unverified_draft
### copper-elesclomol-intestinal-bypass Oral elesclomol without extra copper supplementation rescued neonatal mortality in intestine-specific Ctr1 knockout mice. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug helped use existing dietary copper despite a missing intestinal entry route. organism: Mouse; separate Caenorhabditis elegans experiments tissue_or_cell_type: Intestine and whole-animal development experimental_model: Oral elesclomol in genetically copper-transport-defective animals limitations: Animal rescue does not establish safety or efficacy in people. Intestinal CTR1 loss is a different block from mitochondrial SLC25A3 loss. exposure: Oral drug exposure without additional copper supplementation evidence_span: {"source_cache": "artifacts/copper-research/35433682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ebf1fdc967be53f455383e4edc79468266a5685db3867ca04ce2e2ccc4f2617", "start_char": 0, "end_char": 1449, "text_sha256": "6ebf1fdc967be53f455383e4edc79468266a5685db3867ca04ce2e2ccc4f2617"} [copper-p35433682] Oral Elesclomol Treatment Alleviates Copper Deficiency in Animal Models. (2022). https://pubmed.ncbi.nlm.nih.gov/35433682/ DOI: 10.3389/fcell.2022.856300
Complete structured claim and evidence
Cu(I)-COX17 with two disulfides transferred copper and two electrons to oxidized SCO1, producing copper-loaded SCO1 and apo-COX17 with three disulfides.
Human Cu(I)-COX17 with two disulfides → Human SCO1 with oxidized copper-binding cysteines source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"}
experimental_model
Purified-protein metal and electron transfer experiments
exposure
Defined COX17 and SCO redox states; glutathione reduction
limitations
Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human proteins
plain_language
Copper delivery also changes the receiving protein into a form that can bind it.
primary_references
[copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
tissue_or_cell_type
Mitochondrial intermembrane-space protein system
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 611–622
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-protein metal and electron transfer experiments · source_derived_draft · unverified_draft
### copper-cox17-sco1-handoff Cu(I)-COX17 with two disulfides transferred copper and two electrons to oxidized SCO1, producing copper-loaded SCO1 and apo-COX17 with three disulfides. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper delivery also changes the receiving protein into a form that can bind it. organism: Human proteins tissue_or_cell_type: Mitochondrial intermembrane-space protein system experimental_model: Purified-protein metal and electron transfer experiments limitations: Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly. exposure: Defined COX17 and SCO redox states; glutathione reduction evidence_span: {"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"} [copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
Complete structured claim and evidence
The copper-and-electron-coupled transfer observed with SCO1 did not occur with SCO2 under the same biochemical conditions.
Human Cu(I)-COX17 with two disulfides → Human cytochrome c oxidase assembly protein SCO2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"}
experimental_model
Purified-protein metal and electron transfer experiments
exposure
Defined COX17 and SCO redox states; glutathione reduction
limitations
Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human proteins
plain_language
Related assembly proteins cannot automatically be given the same handoff mechanism.
primary_references
[copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
tissue_or_cell_type
Mitochondrial intermembrane-space protein system
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 637–648
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-protein metal and electron transfer experiments · source_derived_draft · unverified_draft
### copper-cox17-sco2-boundary The copper-and-electron-coupled transfer observed with SCO1 did not occur with SCO2 under the same biochemical conditions. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Related assembly proteins cannot automatically be given the same handoff mechanism. organism: Human proteins tissue_or_cell_type: Mitochondrial intermembrane-space protein system experimental_model: Purified-protein metal and electron transfer experiments limitations: Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly. exposure: Defined COX17 and SCO redox states; glutathione reduction evidence_span: {"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"} [copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
Complete structured claim and evidence
COA6 acted as a thiol reductase for critical cysteine disulfides in SCO1.
Human cytochrome c oxidase assembly factor COA6 → Human cytochrome c oxidase assembly protein SCO1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"}
experimental_model
COA6 knockout HEK293T cells and biochemical protein interaction experiments
exposure
COA6 loss; SCO1/SCO2 disulfide reduction assays
limitations
COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human cells and proteins
plain_language
An assembly factor prepares copper-binding sites for use.
primary_references
[copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
tissue_or_cell_type
Mitochondrial intermembrane space
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 650–661
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · COA6 knockout HEK293T cells and biochemical protein interaction experiments · source_derived_draft · unverified_draft
### copper-coa6-sco1-reduction COA6 acted as a thiol reductase for critical cysteine disulfides in SCO1. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: An assembly factor prepares copper-binding sites for use. organism: Human cells and proteins tissue_or_cell_type: Mitochondrial intermembrane space experimental_model: COA6 knockout HEK293T cells and biochemical protein interaction experiments limitations: COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import. exposure: COA6 loss; SCO1/SCO2 disulfide reduction assays evidence_span: {"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"} [copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
Complete structured claim and evidence
COA6 reduced critical SCO2 disulfides; SCO2 cysteines in its CX3CXnH domain mediated COA6 interaction.
Human cytochrome c oxidase assembly factor COA6 → Human cytochrome c oxidase assembly protein SCO2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"}
experimental_model
COA6 knockout HEK293T cells and biochemical protein interaction experiments
exposure
COA6 loss; SCO1/SCO2 disulfide reduction assays
limitations
COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human cells and proteins
plain_language
The same assembly factor also prepares a second copper-handling protein.
primary_references
[copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
tissue_or_cell_type
Mitochondrial intermembrane space
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 663–674
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · COA6 knockout HEK293T cells and biochemical protein interaction experiments · source_derived_draft · unverified_draft
### copper-coa6-sco2-reduction COA6 reduced critical SCO2 disulfides; SCO2 cysteines in its CX3CXnH domain mediated COA6 interaction. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same assembly factor also prepares a second copper-handling protein. organism: Human cells and proteins tissue_or_cell_type: Mitochondrial intermembrane space experimental_model: COA6 knockout HEK293T cells and biochemical protein interaction experiments limitations: COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import. exposure: COA6 loss; SCO1/SCO2 disulfide reduction assays evidence_span: {"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"} [copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
Complete structured claim and evidence
COA6 loss caused combined respiratory complex I and IV deficiency in human cells.
Human cytochrome c oxidase assembly factor COA6 → Mitochondrial cytochrome c oxidase / respiratory complex IV source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"}
experimental_model
COA6 knockout HEK293T cells and biochemical protein interaction experiments
exposure
COA6 loss; SCO1/SCO2 disulfide reduction assays
limitations
COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human cells and proteins
plain_language
A failure in copper-enzyme assembly can affect more than one respiratory complex.
primary_references
[copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
tissue_or_cell_type
Mitochondrial intermembrane space
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 676–687
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · COA6 knockout HEK293T cells and biochemical protein interaction experiments · source_derived_draft · unverified_draft
### copper-coa6-respiratory-loss COA6 loss caused combined respiratory complex I and IV deficiency in human cells. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A failure in copper-enzyme assembly can affect more than one respiratory complex. organism: Human cells and proteins tissue_or_cell_type: Mitochondrial intermembrane space experimental_model: COA6 knockout HEK293T cells and biochemical protein interaction experiments limitations: COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import. exposure: COA6 loss; SCO1/SCO2 disulfide reduction assays evidence_span: {"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"} [copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
Complete structured claim and evidence
COA6 loss reduced membrane potential and impaired potential-dependent protein import across the inner mitochondrial membrane.
Human cytochrome c oxidase assembly factor COA6 → Membrane-potential-dependent mitochondrial protein import source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"}
experimental_model
COA6 knockout HEK293T cells and biochemical protein interaction experiments
exposure
COA6 loss; SCO1/SCO2 disulfide reduction assays
limitations
COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human cells and proteins
plain_language
The energy deficit can interfere with importing other mitochondrial proteins.
primary_references
[copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
tissue_or_cell_type
Mitochondrial intermembrane space
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 689–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · COA6 knockout HEK293T cells and biochemical protein interaction experiments · source_derived_draft · unverified_draft
### copper-coa6-protein-import COA6 loss reduced membrane potential and impaired potential-dependent protein import across the inner mitochondrial membrane. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The energy deficit can interfere with importing other mitochondrial proteins. organism: Human cells and proteins tissue_or_cell_type: Mitochondrial intermembrane space experimental_model: COA6 knockout HEK293T cells and biochemical protein interaction experiments limitations: COA6 machinery failure is not dietary copper depletion. Protein import effects were selective rather than universal loss of all mitochondrial import. exposure: COA6 loss; SCO1/SCO2 disulfide reduction assays evidence_span: {"source_cache": "artifacts/copper-research/32061935.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a", "start_char": 0, "end_char": 1043, "text_sha256": "7a7828c0b3a9e17878ed230d32af9dd51b667cd1ef0c934fb299f15b5a5e2b0a"} [copper-p32061935] COA6 Facilitates Cytochrome c Oxidase Biogenesis as Thiol-reductase for Copper Metallochaperones in Mitochondria. (2020). https://pubmed.ncbi.nlm.nih.gov/32061935/ DOI: 10.1016/j.jmb.2020.01.036
Complete structured claim and evidence
SCO1-associated cellular copper deficiency reflected increased copper efflux rather than reduced high-affinity uptake in the studied patient-cell models.
Human cytochrome c oxidase assembly protein SCO1 → Cellular copper efflux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/17189203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698", "start_char": 0, "end_char": 950, "text_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698"}
experimental_model
SCO1/SCO2 patient-cell analysis and genetic complementation
exposure
Pathogenic SCO variants; transporter and rescue assays
limitations
Copper effects varied with allele and tissue. A genetic assembly defect does not prove inadequate intake or universal response to copper supplementation.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
The problem was copper leaving the cell too quickly.
primary_references
[copper-p17189203] The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. (2007). https://pubmed.ncbi.nlm.nih.gov/17189203/ DOI: 10.1016/j.cmet.2006.12.001
tissue_or_cell_type
Patient-derived cellular systems
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 702–713
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SCO1/SCO2 patient-cell analysis and genetic complementation · source_derived_draft · unverified_draft
### copper-sco1-copper-efflux SCO1-associated cellular copper deficiency reflected increased copper efflux rather than reduced high-affinity uptake in the studied patient-cell models. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The problem was copper leaving the cell too quickly. organism: Human tissue_or_cell_type: Patient-derived cellular systems experimental_model: SCO1/SCO2 patient-cell analysis and genetic complementation limitations: Copper effects varied with allele and tissue. A genetic assembly defect does not prove inadequate intake or universal response to copper supplementation. exposure: Pathogenic SCO variants; transporter and rescue assays evidence_span: {"source_cache": "artifacts/copper-research/17189203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698", "start_char": 0, "end_char": 950, "text_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698"} [copper-p17189203] The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. (2007). https://pubmed.ncbi.nlm.nih.gov/17189203/ DOI: 10.1016/j.cmet.2006.12.001
Complete structured claim and evidence
SCO2 variants also produced tissue- and allele-specific cellular copper deficiency through increased efflux.
Human cytochrome c oxidase assembly protein SCO2 → Cellular copper efflux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/17189203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698", "start_char": 0, "end_char": 950, "text_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698"}
experimental_model
SCO1/SCO2 patient-cell analysis and genetic complementation
exposure
Pathogenic SCO variants; transporter and rescue assays
limitations
Copper effects varied with allele and tissue. A genetic assembly defect does not prove inadequate intake or universal response to copper supplementation.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
A second mitochondrial assembly protein also influences whole-cell copper balance.
primary_references
[copper-p17189203] The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. (2007). https://pubmed.ncbi.nlm.nih.gov/17189203/ DOI: 10.1016/j.cmet.2006.12.001
tissue_or_cell_type
Patient-derived cellular systems
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 715–726
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SCO1/SCO2 patient-cell analysis and genetic complementation · source_derived_draft · unverified_draft
### copper-sco2-copper-homeostasis SCO2 variants also produced tissue- and allele-specific cellular copper deficiency through increased efflux. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second mitochondrial assembly protein also influences whole-cell copper balance. organism: Human tissue_or_cell_type: Patient-derived cellular systems experimental_model: SCO1/SCO2 patient-cell analysis and genetic complementation limitations: Copper effects varied with allele and tissue. A genetic assembly defect does not prove inadequate intake or universal response to copper supplementation. exposure: Pathogenic SCO variants; transporter and rescue assays evidence_span: {"source_cache": "artifacts/copper-research/17189203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698", "start_char": 0, "end_char": 950, "text_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698"} [copper-p17189203] The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. (2007). https://pubmed.ncbi.nlm.nih.gov/17189203/ DOI: 10.1016/j.cmet.2006.12.001
Complete structured claim and evidence
SCO2 overexpression suppressed the cellular copper-deficiency phenotype; SCO1 overexpression did not provide the same rescue.
Human cytochrome c oxidase assembly protein SCO2 → Biochemically low copper status source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/17189203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698", "start_char": 0, "end_char": 950, "text_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698"}
experimental_model
SCO1/SCO2 patient-cell analysis and genetic complementation
exposure
Pathogenic SCO variants; transporter and rescue assays
limitations
Copper effects varied with allele and tissue. A genetic assembly defect does not prove inadequate intake or universal response to copper supplementation.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
Similar-looking proteins are not interchangeable repairs.
primary_references
[copper-p17189203] The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. (2007). https://pubmed.ncbi.nlm.nih.gov/17189203/ DOI: 10.1016/j.cmet.2006.12.001
tissue_or_cell_type
Patient-derived cellular systems
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 728–739
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SCO1/SCO2 patient-cell analysis and genetic complementation · source_derived_draft · unverified_draft
### copper-sco2-rescue-specificity SCO2 overexpression suppressed the cellular copper-deficiency phenotype; SCO1 overexpression did not provide the same rescue. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Similar-looking proteins are not interchangeable repairs. organism: Human tissue_or_cell_type: Patient-derived cellular systems experimental_model: SCO1/SCO2 patient-cell analysis and genetic complementation limitations: Copper effects varied with allele and tissue. A genetic assembly defect does not prove inadequate intake or universal response to copper supplementation. exposure: Pathogenic SCO variants; transporter and rescue assays evidence_span: {"source_cache": "artifacts/copper-research/17189203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698", "start_char": 0, "end_char": 950, "text_sha256": "7653227df0fe557c484a72eafed6a7a96dc06f5d4f63f7eea4a5b9568949a698"} [copper-p17189203] The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. (2007). https://pubmed.ncbi.nlm.nih.gov/17189203/ DOI: 10.1016/j.cmet.2006.12.001
Complete structured claim and evidence
Ccs deletion did not measurably disrupt overall copper uptake, distribution or incorporation into the other cuproenzymes examined.
Mouse copper chaperone for SOD1 / Ccs → Cellular copper uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/10694572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad", "start_char": 0, "end_char": 1205, "text_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad"}
experimental_model
Ccs knockout mice and radiocopper labeling
exposure
Ccs deletion
limitations
Normal protein abundance can coexist with low activity; the phenotype does not establish a general dietary copper deficiency.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
A broken delivery route can affect one enzyme while other copper routes keep working.
primary_references
[copper-p10694572] Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. (2000). https://pubmed.ncbi.nlm.nih.gov/10694572/ DOI: 10.1073/pnas.040461197
tissue_or_cell_type
Multiple tissues and SOD1 protein
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 754–765
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ccs knockout mice and radiocopper labeling · source_derived_draft · unverified_draft
### copper-ccs-selective-copper-route Ccs deletion did not measurably disrupt overall copper uptake, distribution or incorporation into the other cuproenzymes examined. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A broken delivery route can affect one enzyme while other copper routes keep working. organism: Mouse tissue_or_cell_type: Multiple tissues and SOD1 protein experimental_model: Ccs knockout mice and radiocopper labeling limitations: Normal protein abundance can coexist with low activity; the phenotype does not establish a general dietary copper deficiency. exposure: Ccs deletion evidence_span: {"source_cache": "artifacts/copper-research/10694572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad", "start_char": 0, "end_char": 1205, "text_sha256": "a8c8eb387b7e9d62e19f8de4ab12db826bbda965d5e673391bff49cb7ffe99ad"} [copper-p10694572] Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase. (2000). https://pubmed.ncbi.nlm.nih.gov/10694572/ DOI: 10.1073/pnas.040461197
Complete structured claim and evidence
Recombinant copper-containing human hephaestin oxidized Fe(II), with an apparent substrate Km of 2.1 micromolar.
Human hephaestin / HEPH → Ferrous iron source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"}
experimental_model
Purified recombinant human hephaestin
exposure
Fe(II) substrate and apotransferrin assays
limitations
Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein produced in baby hamster kidney cells
plain_language
A copper enzyme changes iron into the form needed for the next transport step.
primary_references
[copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k
tissue_or_cell_type
Purified soluble hephaestin construct
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 767–778
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human hephaestin · source_derived_draft · unverified_draft
### copper-heph-ferroxidation Recombinant copper-containing human hephaestin oxidized Fe(II), with an apparent substrate Km of 2.1 micromolar. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper enzyme changes iron into the form needed for the next transport step. organism: Human protein produced in baby hamster kidney cells tissue_or_cell_type: Purified soluble hephaestin construct experimental_model: Purified recombinant human hephaestin limitations: Soluble recombinant construct; average measured copper loading of 3.13 atoms is not a universal mature-protein stoichiometry. exposure: Fe(II) substrate and apotransferrin assays evidence_span: {"source_cache": "artifacts/copper-research/16274220.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976", "start_char": 0, "end_char": 1880, "text_sha256": "7f88de566cf98e9aad1df97f91b7b37a4d8e685b842c164db25a196b09c0b976"} [copper-p16274220] Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity. (2005). https://pubmed.ncbi.nlm.nih.gov/16274220/ DOI: 10.1021/bi051559k
Complete structured claim and evidence
Cp-null mice had impaired iron release from hepatocytes and reticuloendothelial cells, while measured iron absorption and plasma turnover were comparable to controls.
Mouse ceruloplasmin Cp → Mouse release of stored iron from hepatocytes and reticuloendothelial cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"}
experimental_model
Ceruloplasmin gene disruption and ferrokinetics
exposure
Cp knockout followed through one year
limitations
Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The main defect was moving stored iron out of cells.
primary_references
[copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812
tissue_or_cell_type
Liver, spleen and reticuloendothelial cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 793–804
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ceruloplasmin gene disruption and ferrokinetics · source_derived_draft · unverified_draft
### copper-cp-iron-mobilization Cp-null mice had impaired iron release from hepatocytes and reticuloendothelial cells, while measured iron absorption and plasma turnover were comparable to controls. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The main defect was moving stored iron out of cells. organism: Mouse tissue_or_cell_type: Liver, spleen and reticuloendothelial cells experimental_model: Ceruloplasmin gene disruption and ferrokinetics limitations: Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally. exposure: Cp knockout followed through one year evidence_span: {"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"} [copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812
Complete structured claim and evidence
By one year, Cp-null mice had three- to sixfold higher liver and spleen iron with increased serum ferritin.
Mouse ceruloplasmin Cp → Mouse hepatic iron accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"}
experimental_model
Ceruloplasmin gene disruption and ferrokinetics
exposure
Cp knockout followed through one year
limitations
Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
High storage markers can coexist with an iron-distribution problem.
primary_references
[copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812
tissue_or_cell_type
Liver, spleen and reticuloendothelial cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 806–817
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ceruloplasmin gene disruption and ferrokinetics · source_derived_draft · unverified_draft
### copper-cp-liver-iron By one year, Cp-null mice had three- to sixfold higher liver and spleen iron with increased serum ferritin. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: High storage markers can coexist with an iron-distribution problem. organism: Mouse tissue_or_cell_type: Liver, spleen and reticuloendothelial cells experimental_model: Ceruloplasmin gene disruption and ferrokinetics limitations: Genetic ceruloplasmin absence differs from dietary copper shortage; normal intestinal absorption in this experiment does not imply all copper-deficient states absorb iron normally. exposure: Cp knockout followed through one year evidence_span: {"source_cache": "artifacts/copper-research/10485908.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067", "start_char": 0, "end_char": 1368, "text_sha256": "2feaccc19bf8f4480643a918de9300a6c224935b47c24e251d96050599e3b067"} [copper-p10485908] Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. (1999). https://pubmed.ncbi.nlm.nih.gov/10485908/ DOI: 10.1073/pnas.96.19.10812
Complete structured claim and evidence
Whole-body double deletion loaded iron into duodenum, liver, heart and pancreas; intestine-specific Heph deletion with global Cp loss produced a more restricted distribution.
Mouse hephaestin Heph → Mouse iron accumulation across multiple organs source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"}
experimental_model
Whole-body and intestine-specific Heph/Cp double-knockout mice
exposure
Combined or tissue-specific deletion; oral iron tracer
limitations
Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Where the enzyme is missing changes where iron gets trapped.
primary_references
[copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
tissue_or_cell_type
Intestine, liver, heart, pancreas and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 832–843
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and intestine-specific Heph/Cp double-knockout mice · source_derived_draft · unverified_draft
### copper-heph-cp-organ-loading Whole-body double deletion loaded iron into duodenum, liver, heart and pancreas; intestine-specific Heph deletion with global Cp loss produced a more restricted distribution. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Where the enzyme is missing changes where iron gets trapped. organism: Mouse tissue_or_cell_type: Intestine, liver, heart, pancreas and blood experimental_model: Whole-body and intestine-specific Heph/Cp double-knockout mice limitations: Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route. exposure: Combined or tissue-specific deletion; oral iron tracer evidence_span: {"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"} [copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
Complete structured claim and evidence
Both Heph/Cp double-knockout models still absorbed oral iron tracer, but retained an abnormally high fraction in the liver.
Mouse hephaestin Heph → Mouse intestinal iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"}
experimental_model
Whole-body and intestine-specific Heph/Cp double-knockout mice
exposure
Combined or tissue-specific deletion; oral iron tracer
limitations
Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Absorption and useful distribution are different steps.
primary_references
[copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
tissue_or_cell_type
Intestine, liver, heart, pancreas and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 845–856
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and intestine-specific Heph/Cp double-knockout mice · source_derived_draft · unverified_draft
### copper-heph-cp-residual-absorption Both Heph/Cp double-knockout models still absorbed oral iron tracer, but retained an abnormally high fraction in the liver. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorption and useful distribution are different steps. organism: Mouse tissue_or_cell_type: Intestine, liver, heart, pancreas and blood experimental_model: Whole-body and intestine-specific Heph/Cp double-knockout mice limitations: Double knockouts differ from low dietary copper. Detectable iron absorption remained, so these enzymes are not an absolute all-or-none gate for every absorption route. exposure: Combined or tissue-specific deletion; oral iron tracer evidence_span: {"source_cache": "artifacts/copper-research/30182051.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72", "start_char": 0, "end_char": 1882, "text_sha256": "57ed2ee0540cc9ec88748eaa23af1a38d307271d9e7ea6367a24d412622a4b72"} [copper-p30182051] Severe Iron Metabolism Defects in Mice With Double Knockout of the Multicopper Ferroxidases Hephaestin and Ceruloplasmin. (2018). https://pubmed.ncbi.nlm.nih.gov/30182051/ DOI: 10.1016/j.jcmgh.2018.06.006
Complete structured claim and evidence
Copper-deficient male and female rats absorbed about 60% and 70%, respectively, of the iron absorbed by copper-adequate controls.
Copper → Rat intestinal iron absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"}
experimental_model
Controlled copper-deficient versus adequate diets with radiolabeled iron
exposure
Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings
limitations
Animal depletion regimens are not human thresholds. Iron redistribution differed by sex.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat
plain_language
Adding iron alone does not describe the copper-dependent processing step.
primary_references
[copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
tissue_or_cell_type
Duodenal enterocytes and whole-body iron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 871–882
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled copper-deficient versus adequate diets with radiolabeled iron · source_derived_draft · unverified_draft
### copper-cud-iron-absorption Copper-deficient male and female rats absorbed about 60% and 70%, respectively, of the iron absorbed by copper-adequate controls. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding iron alone does not describe the copper-dependent processing step. organism: Rat tissue_or_cell_type: Duodenal enterocytes and whole-body iron experimental_model: Controlled copper-deficient versus adequate diets with radiolabeled iron limitations: Animal depletion regimens are not human thresholds. Iron redistribution differed by sex. exposure: Less than 0.3 versus 5 mg copper/kg diet; male and female weanlings evidence_span: {"source_cache": "artifacts/copper-research/15623839.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac", "start_char": 0, "end_char": 1613, "text_sha256": "5e3723e4fdd961caf66979e26614d98cbfbd65f38ba48232428e5302c054c3ac"} [copper-p15623839] Dietary copper deficiency reduces iron absorption and duodenal enterocyte hephaestin protein in male and female rats. (2005). https://pubmed.ncbi.nlm.nih.gov/15623839/ DOI: 10.1093/jn/135.1.92
Complete structured claim and evidence
Dietary copper deficiency caused little ferroportin mRNA change; protein responses varied and did not account for the anemia across the rodent models.
Copper → Rodent tissue ferroportin protein abundance source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/22294464.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008de3f1f584a29a0ce082e6423042ed21585064b2dc900802103fc00b3fee8e", "start_char": 0, "end_char": 1578, "text_sha256": "008de3f1f584a29a0ce082e6423042ed21585064b2dc900802103fc00b3fee8e"}
experimental_model
Dietary copper-deficient rat and mouse tissue comparisons
exposure
Dietary copper depletion
limitations
Tissue ferroportin responses were complex and did not explain copper-deficiency anemia. Do not generalize genetic GPI-ceruloplasmin absence into universal ferroportin destruction during nutritional copper deficiency.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat and mouse
plain_language
There is no single demonstrated switch that destroys every iron exporter when copper falls.
primary_references
[copper-p22294464] Copper deficiency has minimal impact on ferroportin expression or function. (2012). https://pubmed.ncbi.nlm.nih.gov/22294464/ DOI: 10.1007/s10534-012-9521-2
tissue_or_cell_type
Liver, spleen and intestinal iron-related tissues
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 884–895
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary copper-deficient rat and mouse tissue comparisons · source_derived_draft · unverified_draft
### copper-cud-ferroportin-boundary Dietary copper deficiency caused little ferroportin mRNA change; protein responses varied and did not account for the anemia across the rodent models. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: There is no single demonstrated switch that destroys every iron exporter when copper falls. organism: Rat and mouse tissue_or_cell_type: Liver, spleen and intestinal iron-related tissues experimental_model: Dietary copper-deficient rat and mouse tissue comparisons limitations: Tissue ferroportin responses were complex and did not explain copper-deficiency anemia. Do not generalize genetic GPI-ceruloplasmin absence into universal ferroportin destruction during nutritional copper deficiency. exposure: Dietary copper depletion evidence_span: {"source_cache": "artifacts/copper-research/22294464.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "008de3f1f584a29a0ce082e6423042ed21585064b2dc900802103fc00b3fee8e", "start_char": 0, "end_char": 1578, "text_sha256": "008de3f1f584a29a0ce082e6423042ed21585064b2dc900802103fc00b3fee8e"} [copper-p22294464] Copper deficiency has minimal impact on ferroportin expression or function. (2012). https://pubmed.ncbi.nlm.nih.gov/22294464/ DOI: 10.1007/s10534-012-9521-2
Complete structured claim and evidence
ATP7A silencing impaired iron uptake and efflux in differentiated human Caco-2 cells.
Human copper-transporting ATPase ATP7A → Iron uptake and efflux in cultured intestinal epithelia source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/27714044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37", "start_char": 0, "end_char": 1780, "text_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37"}
experimental_model
ATP7A knockdown in differentiated intestinal cell cultures
exposure
ATP7A knockdown and radiolabeled iron transport
limitations
Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
A copper transporter also helps the intestinal iron-handling system function.
primary_references
[copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b
tissue_or_cell_type
Caco-2 cells
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 897–908
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ATP7A knockdown in differentiated intestinal cell cultures · source_derived_draft · unverified_draft
### copper-human-atp7a-iron ATP7A silencing impaired iron uptake and efflux in differentiated human Caco-2 cells. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper transporter also helps the intestinal iron-handling system function. organism: Human tissue_or_cell_type: Caco-2 cells experimental_model: ATP7A knockdown in differentiated intestinal cell cultures limitations: Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line. exposure: ATP7A knockdown and radiolabeled iron transport evidence_span: {"source_cache": "artifacts/copper-research/27714044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37", "start_char": 0, "end_char": 1780, "text_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37"} [copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b
Complete structured claim and evidence
Rat Atp7a knockdown increased hephaestin expression more than tenfold and increased ferroxidase activity, even though net iron uptake and efflux fell.
Rat copper-transporting ATPase Atp7a → Rat hephaestin Heph source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/27714044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37", "start_char": 0, "end_char": 1780, "text_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37"}
experimental_model
ATP7A knockdown in differentiated intestinal cell cultures
exposure
ATP7A knockdown and radiolabeled iron transport
limitations
Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat
plain_language
Compensatory enzyme increases did not repair the overall transport chain.
primary_references
[copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b
tissue_or_cell_type
IEC-6 cells
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 910–921
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ATP7A knockdown in differentiated intestinal cell cultures · source_derived_draft · unverified_draft
### copper-rat-atp7a-heph-compensation Rat Atp7a knockdown increased hephaestin expression more than tenfold and increased ferroxidase activity, even though net iron uptake and efflux fell. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Compensatory enzyme increases did not repair the overall transport chain. organism: Rat tissue_or_cell_type: IEC-6 cells experimental_model: ATP7A knockdown in differentiated intestinal cell cultures limitations: Reductionist cell models; increased enzyme activity did not guarantee increased net iron flux. Molecular expression details were measured in the rat line. exposure: ATP7A knockdown and radiolabeled iron transport evidence_span: {"source_cache": "artifacts/copper-research/27714044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37", "start_char": 0, "end_char": 1780, "text_sha256": "5e8791edb75475ba74e95cddc330c06512ef3b9c02a0c5a6b203327c047dff37"} [copper-p27714044] Knockdown of copper-transporting ATPase 1 (Atp7a) impairs iron flux in fully-differentiated rat (IEC-6) and human (Caco-2) intestinal epithelial cells. (2016). https://pubmed.ncbi.nlm.nih.gov/27714044/ DOI: 10.1039/c6mt00126b
Complete structured claim and evidence
Atp7a silencing reduced LOX/LOXL activity in mouse mammary and lung carcinoma models.
Mouse copper-transporting ATPase Atp7a → Mouse LOX and LOXL enzyme activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/30890638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816", "start_char": 0, "end_char": 1001, "text_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816"}
experimental_model
Atp7a silencing and orthotopic tumor experiments
exposure
Atp7a silencing
limitations
Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse; separate human survival association
plain_language
The copper delivery pump helps activate extracellular cross-linking enzymes.
primary_references
[copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116
tissue_or_cell_type
4T1 mammary carcinoma and Lewis lung carcinoma
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 923–934
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atp7a silencing and orthotopic tumor experiments · source_derived_draft · unverified_draft
### copper-atp7a-lox-loading Atp7a silencing reduced LOX/LOXL activity in mouse mammary and lung carcinoma models. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The copper delivery pump helps activate extracellular cross-linking enzymes. organism: Mouse; separate human survival association tissue_or_cell_type: 4T1 mammary carcinoma and Lewis lung carcinoma experimental_model: Atp7a silencing and orthotopic tumor experiments limitations: Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative. exposure: Atp7a silencing evidence_span: {"source_cache": "artifacts/copper-research/30890638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816", "start_char": 0, "end_char": 1001, "text_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816"} [copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116
Complete structured claim and evidence
Atp7a silencing reduced LOX-associated metastatic behavior, including focal-adhesion signaling and lung myeloid recruitment in the tested mammary tumor model.
Mouse copper-transporting ATPase Atp7a → Metastasis in mouse tumor models source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/30890638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816", "start_char": 0, "end_char": 1001, "text_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816"}
experimental_model
Atp7a silencing and orthotopic tumor experiments
exposure
Atp7a silencing
limitations
Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse; separate human survival association
plain_language
A normal tissue-building pathway can be used by tumors in a different context.
primary_references
[copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116
tissue_or_cell_type
4T1 mammary carcinoma and Lewis lung carcinoma
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 936–947
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atp7a silencing and orthotopic tumor experiments · source_derived_draft · unverified_draft
### copper-atp7a-lox-metastasis Atp7a silencing reduced LOX-associated metastatic behavior, including focal-adhesion signaling and lung myeloid recruitment in the tested mammary tumor model. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal tissue-building pathway can be used by tumors in a different context. organism: Mouse; separate human survival association tissue_or_cell_type: 4T1 mammary carcinoma and Lewis lung carcinoma experimental_model: Atp7a silencing and orthotopic tumor experiments limitations: Tumor models are not evidence that dietary copper causes cancer or that copper restriction treats it; the human survival component was associative. exposure: Atp7a silencing evidence_span: {"source_cache": "artifacts/copper-research/30890638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816", "start_char": 0, "end_char": 1001, "text_sha256": "bc966add777f73d031bc34724fb8a07c6f4df2493086e13df7ae4521dee74816"} [copper-p30890638] ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis. (2019). https://pubmed.ncbi.nlm.nih.gov/30890638/ DOI: 10.1073/pnas.1817473116
Complete structured claim and evidence
Atp7a overexpression restored reduced SOD3 specific activity in diabetic mouse vessels.
Mouse copper-transporting ATPase Atp7a → Mouse vascular SOD3 activity per protein amount source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"}
experimental_model
Genetic and streptozotocin diabetes mouse models with vascular rescue assays
exposure
Diabetes, Atp7a overexpression, copper or insulin ex vivo
limitations
Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Restoring copper delivery improved the enzyme’s activity.
primary_references
[copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228
tissue_or_cell_type
Aortas, mesenteric vessels and vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 949–960
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and streptozotocin diabetes mouse models with vascular rescue assays · source_derived_draft · unverified_draft
### copper-atp7a-sod3 Atp7a overexpression restored reduced SOD3 specific activity in diabetic mouse vessels. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring copper delivery improved the enzyme’s activity. organism: Mouse tissue_or_cell_type: Aortas, mesenteric vessels and vascular smooth muscle experimental_model: Genetic and streptozotocin diabetes mouse models with vascular rescue assays limitations: Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect. exposure: Diabetes, Atp7a overexpression, copper or insulin ex vivo evidence_span: {"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"} [copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228
Complete structured claim and evidence
SOD3 gene transfer rescued impaired endothelium-dependent relaxation in the tested diabetic mouse arteries.
Mouse extracellular superoxide dismutase Sod3 → Mouse endothelium-dependent vascular relaxation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"}
experimental_model
Genetic and streptozotocin diabetes mouse models with vascular rescue assays
exposure
Diabetes, Atp7a overexpression, copper or insulin ex vivo
limitations
Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The extracellular antioxidant system helped the blood vessel respond normally.
primary_references
[copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228
tissue_or_cell_type
Aortas, mesenteric vessels and vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 962–973
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and streptozotocin diabetes mouse models with vascular rescue assays · source_derived_draft · unverified_draft
### copper-sod3-vascular-relaxation SOD3 gene transfer rescued impaired endothelium-dependent relaxation in the tested diabetic mouse arteries. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The extracellular antioxidant system helped the blood vessel respond normally. organism: Mouse tissue_or_cell_type: Aortas, mesenteric vessels and vascular smooth muscle experimental_model: Genetic and streptozotocin diabetes mouse models with vascular rescue assays limitations: Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect. exposure: Diabetes, Atp7a overexpression, copper or insulin ex vivo evidence_span: {"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"} [copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228
Complete structured claim and evidence
Insulin treatment increased ATP7A expression in vascular smooth muscle cells and restored SOD3 activity in diabetic mouse vessel culture.
Insulin → Mouse copper-transporting ATPase Atp7a source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"}
experimental_model
Genetic and streptozotocin diabetes mouse models with vascular rescue assays
exposure
Diabetes, Atp7a overexpression, copper or insulin ex vivo
limitations
Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
Hormone signaling can change whether a copper-dependent enzyme receives its metal.
primary_references
[copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228
tissue_or_cell_type
Aortas, mesenteric vessels and vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 975–986
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and streptozotocin diabetes mouse models with vascular rescue assays · source_derived_draft · unverified_draft
### copper-insulin-atp7a Insulin treatment increased ATP7A expression in vascular smooth muscle cells and restored SOD3 activity in diabetic mouse vessel culture. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Hormone signaling can change whether a copper-dependent enzyme receives its metal. organism: Mouse tissue_or_cell_type: Aortas, mesenteric vessels and vascular smooth muscle experimental_model: Genetic and streptozotocin diabetes mouse models with vascular rescue assays limitations: Local transporter loss and hypoinsulinemia are not proof of dietary copper deficiency or a human supplementation effect. exposure: Diabetes, Atp7a overexpression, copper or insulin ex vivo evidence_span: {"source_cache": "artifacts/copper-research/23884884.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249", "start_char": 0, "end_char": 1831, "text_sha256": "85b24243a5eec9d9447299976023325f133d18d979f5be612845f4d2bbc28249"} [copper-p23884884] Copper transporter ATP7A protects against endothelial dysfunction in type 1 diabetic mice by regulating extracellular superoxide dismutase. (2013). https://pubmed.ncbi.nlm.nih.gov/23884884/ DOI: 10.2337/db12-1228
Complete structured claim and evidence
Tyrosinase copper loading was transient and inefficient in the Golgi; ATP7A supplied copper for reloading in melanosomes.
Mouse copper-transporting ATPase Atp7a → Copper loading of mouse tyrosinase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"}
experimental_model
Mouse melanocyte localization and tyrosinase metallation experiments
exposure
ATP7A/BLOC-1-dependent localization
limitations
Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The pigment enzyme needs copper at its final workplace, not just earlier during production.
primary_references
[copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163
tissue_or_cell_type
Golgi and melanosomes
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 988–999
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse melanocyte localization and tyrosinase metallation experiments · source_derived_draft · unverified_draft
### copper-atp7a-tyr-reloading Tyrosinase copper loading was transient and inefficient in the Golgi; ATP7A supplied copper for reloading in melanosomes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pigment enzyme needs copper at its final workplace, not just earlier during production. organism: Mouse tissue_or_cell_type: Golgi and melanosomes experimental_model: Mouse melanocyte localization and tyrosinase metallation experiments limitations: Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency. exposure: ATP7A/BLOC-1-dependent localization evidence_span: {"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"} [copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163
Complete structured claim and evidence
ATP7A localization to melanosomes depended on BLOC-1 in mouse melanocytes.
Mouse biogenesis of lysosome-related organelles complex 1 / BLOC-1 → Mouse ATP7A localization to melanosomes source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"}
experimental_model
Mouse melanocyte localization and tyrosinase metallation experiments
exposure
ATP7A/BLOC-1-dependent localization
limitations
Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
A trafficking complex directs the copper pump to the pigment compartment.
primary_references
[copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163
tissue_or_cell_type
Golgi and melanosomes
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1001–1012
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse melanocyte localization and tyrosinase metallation experiments · source_derived_draft · unverified_draft
### copper-bloc1-atp7a-location ATP7A localization to melanosomes depended on BLOC-1 in mouse melanocytes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A trafficking complex directs the copper pump to the pigment compartment. organism: Mouse tissue_or_cell_type: Golgi and melanosomes experimental_model: Mouse melanocyte localization and tyrosinase metallation experiments limitations: Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency. exposure: ATP7A/BLOC-1-dependent localization evidence_span: {"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"} [copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163
Complete structured claim and evidence
Human diamine oxidase has a substrate pocket adapted to diamines including histamine, distinct from that of AOC3.
Human diamine oxidase / AOC1 / DAO → Histamine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/19764817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6", "start_char": 0, "end_char": 1343, "text_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6"}
experimental_model
Crystallography of recombinant human diamine oxidase and inhibitor complexes
exposure
Native structure and inhibitor binding
limitations
Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human AOC1 expressed in insect cells
plain_language
Related copper enzymes process different amines.
primary_references
[copper-p19764817] Structure and inhibition of human diamine oxidase. (2009). https://pubmed.ncbi.nlm.nih.gov/19764817/ DOI: 10.1021/bi9014192
tissue_or_cell_type
Purified protein
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1027–1038
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography of recombinant human diamine oxidase and inhibitor complexes · source_derived_draft · unverified_draft
### copper-aoc1-histamine-specificity Human diamine oxidase has a substrate pocket adapted to diamines including histamine, distinct from that of AOC3. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Related copper enzymes process different amines. organism: Human AOC1 expressed in insect cells tissue_or_cell_type: Purified protein experimental_model: Crystallography of recombinant human diamine oxidase and inhibitor complexes limitations: Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants. exposure: Native structure and inhibitor binding evidence_span: {"source_cache": "artifacts/copper-research/19764817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6", "start_char": 0, "end_char": 1343, "text_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6"} [copper-p19764817] Structure and inhibition of human diamine oxidase. (2009). https://pubmed.ncbi.nlm.nih.gov/19764817/ DOI: 10.1021/bi9014192
Complete structured claim and evidence
The human AOC3 structure contained an active-site copper ion and TPQ in its active off-copper conformation.
Human copper amine oxidase AOC3 / vascular adhesion protein 1 / VAP-1 → Protein-derived topaquinone / TPQ cofactor source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/16239734.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "24ea102446aeff31a53b9302d191c0bc572100f8ee82b6ccb1a665432151662b", "start_char": 0, "end_char": 1408, "text_sha256": "24ea102446aeff31a53b9302d191c0bc572100f8ee82b6ccb1a665432151662b"}
experimental_model
X-ray structures of soluble human VAP-1 and inhibitor complex
exposure
Native and inhibitor-bound structure
limitations
Soluble protein structure; proposed gate and adhesion-motif functions are not proven clinical effects of copper intake.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein
plain_language
A separate copper amine oxidase has its own catalytic arrangement.
primary_references
[copper-p16239734] Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1. (2005). https://pubmed.ncbi.nlm.nih.gov/16239734/ DOI: 10.1107/s0907444905028805
tissue_or_cell_type
Purified truncated soluble AOC3
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1040–1051
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of soluble human VAP-1 and inhibitor complex · source_derived_draft · unverified_draft
### copper-aoc3-copper-tpq The human AOC3 structure contained an active-site copper ion and TPQ in its active off-copper conformation. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate copper amine oxidase has its own catalytic arrangement. organism: Human protein tissue_or_cell_type: Purified truncated soluble AOC3 experimental_model: X-ray structures of soluble human VAP-1 and inhibitor complex limitations: Soluble protein structure; proposed gate and adhesion-motif functions are not proven clinical effects of copper intake. exposure: Native and inhibitor-bound structure evidence_span: {"source_cache": "artifacts/copper-research/16239734.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "24ea102446aeff31a53b9302d191c0bc572100f8ee82b6ccb1a665432151662b", "start_char": 0, "end_char": 1408, "text_sha256": "24ea102446aeff31a53b9302d191c0bc572100f8ee82b6ccb1a665432151662b"} [copper-p16239734] Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1. (2005). https://pubmed.ncbi.nlm.nih.gov/16239734/ DOI: 10.1107/s0907444905028805
Complete structured claim and evidence
Ceruloplasmin copper incorporation was cooperative, and its final conformational state required occupation of all six copper-binding sites in the tested system.
Human ceruloplasmin / CP → Copper-loaded human holoceruloplasmin source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/12351628.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3", "start_char": 0, "end_char": 1541, "text_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3"}
experimental_model
Human ceruloplasmin expression, radiocopper labeling and in-vitro loading
exposure
Wild-type and copper-site mutants including G631R
limitations
The final conformation required six occupied sites in these assays; no hierarchy was apparent. Do not confuse this structural requirement with circulating protein concentration.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein expressed in Chinese hamster ovary cells
plain_language
The protein needs coordinated metal loading to reach its mature form.
primary_references
[copper-p12351628] Mechanisms of copper incorporation into human ceruloplasmin. (2002). https://pubmed.ncbi.nlm.nih.gov/12351628/ DOI: 10.1074/jbc.m206246200
tissue_or_cell_type
Secretory protein biosynthesis
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1053–1064
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ceruloplasmin expression, radiocopper labeling and in-vitro loading · source_derived_draft · unverified_draft
### copper-cp-six-site-loading Ceruloplasmin copper incorporation was cooperative, and its final conformational state required occupation of all six copper-binding sites in the tested system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protein needs coordinated metal loading to reach its mature form. organism: Human protein expressed in Chinese hamster ovary cells tissue_or_cell_type: Secretory protein biosynthesis experimental_model: Human ceruloplasmin expression, radiocopper labeling and in-vitro loading limitations: The final conformation required six occupied sites in these assays; no hierarchy was apparent. Do not confuse this structural requirement with circulating protein concentration. exposure: Wild-type and copper-site mutants including G631R evidence_span: {"source_cache": "artifacts/copper-research/12351628.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3", "start_char": 0, "end_char": 1541, "text_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3"} [copper-p12351628] Mechanisms of copper incorporation into human ceruloplasmin. (2002). https://pubmed.ncbi.nlm.nih.gov/12351628/ DOI: 10.1074/jbc.m206246200
Complete structured claim and evidence
The aceruloplasminemia-associated G631R variant was synthesized and secreted as apoceruloplasmin in the cell-expression study.
Human ceruloplasmin / CP → Human ceruloplasmin without incorporated copper source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/12351628.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3", "start_char": 0, "end_char": 1541, "text_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3"}
experimental_model
Human ceruloplasmin expression, radiocopper labeling and in-vitro loading
exposure
Wild-type and copper-site mutants including G631R
limitations
The final conformation required six occupied sites in these assays; no hierarchy was apparent. Do not confuse this structural requirement with circulating protein concentration.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein expressed in Chinese hamster ovary cells
plain_language
A copper-handling protein can be produced and released yet still lack its metal.
primary_references
[copper-p12351628] Mechanisms of copper incorporation into human ceruloplasmin. (2002). https://pubmed.ncbi.nlm.nih.gov/12351628/ DOI: 10.1074/jbc.m206246200
tissue_or_cell_type
Secretory protein biosynthesis
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1066–1077
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ceruloplasmin expression, radiocopper labeling and in-vitro loading · source_derived_draft · unverified_draft
### copper-cp-variant-apo The aceruloplasminemia-associated G631R variant was synthesized and secreted as apoceruloplasmin in the cell-expression study. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper-handling protein can be produced and released yet still lack its metal. organism: Human protein expressed in Chinese hamster ovary cells tissue_or_cell_type: Secretory protein biosynthesis experimental_model: Human ceruloplasmin expression, radiocopper labeling and in-vitro loading limitations: The final conformation required six occupied sites in these assays; no hierarchy was apparent. Do not confuse this structural requirement with circulating protein concentration. exposure: Wild-type and copper-site mutants including G631R evidence_span: {"source_cache": "artifacts/copper-research/12351628.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3", "start_char": 0, "end_char": 1541, "text_sha256": "4492680e4d410b1e32f77dea6aa0c26b2303b26d4fadfef25a350338ac365de3"} [copper-p12351628] Mechanisms of copper incorporation into human ceruloplasmin. (2002). https://pubmed.ncbi.nlm.nih.gov/12351628/ DOI: 10.1074/jbc.m206246200
Complete structured claim and evidence
Human DBH displayed open and closed active-site conformations; the closed structure placed its two copper-binding sites about 4–5 angstroms apart.
Human dopamine beta-hydroxylase / DBH → Copper source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/27152332.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09", "start_char": 0, "end_char": 1325, "text_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09"}
experimental_model
Human DBH X-ray crystallography
exposure
Crystal structure at 2.9 angstrom resolution
limitations
Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein
plain_language
The enzyme changes the spacing of its copper-binding regions; their precise catalytic cycle remains under study.
primary_references
[copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980
tissue_or_cell_type
Purified dimeric enzyme
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1092–1103
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DBH X-ray crystallography · source_derived_draft · unverified_draft
### copper-dbh-copper-site-conformations Human DBH displayed open and closed active-site conformations; the closed structure placed its two copper-binding sites about 4–5 angstroms apart. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme changes the spacing of its copper-binding regions; their precise catalytic cycle remains under study. organism: Human protein tissue_or_cell_type: Purified dimeric enzyme experimental_model: Human DBH X-ray crystallography limitations: Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake. exposure: Crystal structure at 2.9 angstrom resolution evidence_span: {"source_cache": "artifacts/copper-research/27152332.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09", "start_char": 0, "end_char": 1325, "text_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09"} [copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980
Complete structured claim and evidence
The 605 mg/day vitamin C period reduced ceruloplasmin oxidase activity by about 21% in the controlled feeding study.
L-Ascorbic acid → Circulating ceruloplasmin oxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"}
experimental_model
Controlled sequential dietary vitamin C intervention
exposure
Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods
limitations
Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human men
plain_language
A copper-related enzyme measurement changed with vitamin C intake.
primary_references
[copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109
tissue_or_cell_type
Copper absorption, retention and circulating markers
trigger_kind
biomarker_context Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1105–1116
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled sequential dietary vitamin C intervention · source_derived_draft · unverified_draft
### copper-ascorbate-cp-oxidase The 605 mg/day vitamin C period reduced ceruloplasmin oxidase activity by about 21% in the controlled feeding study. Condition category: biomarker_context nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper-related enzyme measurement changed with vitamin C intake. organism: Human men tissue_or_cell_type: Copper absorption, retention and circulating markers experimental_model: Controlled sequential dietary vitamin C intervention limitations: Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established. exposure: Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods evidence_span: {"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"} [copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109
Complete structured claim and evidence
The study found no significant vitamin-C-period effect on copper absorption, retention, serum copper or ceruloplasmin protein despite the oxidase-activity change.
L-Ascorbic acid → Whole-body copper retention source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"}
experimental_model
Controlled sequential dietary vitamin C intervention
exposure
Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods
limitations
Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human men
plain_language
The activity change did not demonstrate loss of body copper.
primary_references
[copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109
tissue_or_cell_type
Copper absorption, retention and circulating markers
trigger_kind
biomarker_context Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1118–1129
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled sequential dietary vitamin C intervention · source_derived_draft · unverified_draft
### copper-ascorbate-copper-retention The study found no significant vitamin-C-period effect on copper absorption, retention, serum copper or ceruloplasmin protein despite the oxidase-activity change. Condition category: biomarker_context nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The activity change did not demonstrate loss of body copper. organism: Human men tissue_or_cell_type: Copper absorption, retention and circulating markers experimental_model: Controlled sequential dietary vitamin C intervention limitations: Short sequential study; ceruloplasmin activity differs from protein concentration and whole-body copper stores. No universal vitamin C threshold is established. exposure: Fourteen-week feeding study: 65, 5, 605 and 5 mg vitamin C/day in successive periods evidence_span: {"source_cache": "artifacts/copper-research/3694287.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68", "start_char": 0, "end_char": 1031, "text_sha256": "37e70fcbc672023cd6c3616b4a1171c6ded4caafe4e3c14d4f80c6abca490e68"} [copper-p3694287] Effect of varying ascorbic acid intakes on copper absorption and ceruloplasmin levels of young men. (1987). https://pubmed.ncbi.nlm.nih.gov/3694287/ DOI: 10.1093/jn/117.12.2109
Complete structured claim and evidence
Ceruloplasmin oxidase activity decreased during 1500 mg/day vitamin C supplementation; the serum copper decline was not statistically significant.
L-Ascorbic acid → Circulating ceruloplasmin oxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/6837490.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03", "start_char": 0, "end_char": 1026, "text_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03"}
experimental_model
Within-person vitamin C supplementation and withdrawal study
exposure
1500 mg vitamin C/day for 64 days on self-selected diets
limitations
No independent placebo control; measured values remained within cited physiological ranges, and serum copper decline during supplementation was not significant.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human men
plain_language
Enzyme activity was more responsive than the copper concentration measurement in this small study.
primary_references
[copper-p6837490] Influence of ascorbic acid supplementation on copper status in young adult men. (1983). https://pubmed.ncbi.nlm.nih.gov/6837490/ DOI: 10.1093/ajcn/37.4.553
tissue_or_cell_type
Circulating copper and ceruloplasmin activity
trigger_kind
biomarker_context Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1131–1142
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person vitamin C supplementation and withdrawal study · source_derived_draft · unverified_draft
### copper-high-vitc-cp-activity Ceruloplasmin oxidase activity decreased during 1500 mg/day vitamin C supplementation; the serum copper decline was not statistically significant. Condition category: biomarker_context nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Enzyme activity was more responsive than the copper concentration measurement in this small study. organism: Human men tissue_or_cell_type: Circulating copper and ceruloplasmin activity experimental_model: Within-person vitamin C supplementation and withdrawal study limitations: No independent placebo control; measured values remained within cited physiological ranges, and serum copper decline during supplementation was not significant. exposure: 1500 mg vitamin C/day for 64 days on self-selected diets evidence_span: {"source_cache": "artifacts/copper-research/6837490.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03", "start_char": 0, "end_char": 1026, "text_sha256": "628dd5cb00ff83cf6d31ff973073a19041de727a370d8652715bb6452b29bc03"} [copper-p6837490] Influence of ascorbic acid supplementation on copper status in young adult men. (1983). https://pubmed.ncbi.nlm.nih.gov/6837490/ DOI: 10.1093/ajcn/37.4.553
Complete structured claim and evidence
High dietary iron reduced copper absorption in copper-deficient rats but not in copper-adequate rats in the factorial study.
Iron → Intestinal copper absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/3337044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc", "start_char": 0, "end_char": 882, "text_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc"}
experimental_model
Factorial dietary copper, iron and ascorbate feeding experiment
exposure
Copper 0.42 versus 5.74 micrograms/g diet; iron 38 versus 191 micrograms/g; ascorbate 0 versus 1%, for 20 days
limitations
Animal feed concentrations cannot be converted into a human supplement rule. Baseline copper status modified effects.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat
plain_language
The same iron exposure had different effects depending on the starting copper supply.
primary_references
[copper-p3337044] Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3337044/ DOI: 10.1093/ajcn/47.1.96
tissue_or_cell_type
Intestinal uptake, blood and tissues
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1144–1155
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial dietary copper, iron and ascorbate feeding experiment · source_derived_draft · unverified_draft
### copper-iron-lowcu-absorption High dietary iron reduced copper absorption in copper-deficient rats but not in copper-adequate rats in the factorial study. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same iron exposure had different effects depending on the starting copper supply. organism: Rat tissue_or_cell_type: Intestinal uptake, blood and tissues experimental_model: Factorial dietary copper, iron and ascorbate feeding experiment limitations: Animal feed concentrations cannot be converted into a human supplement rule. Baseline copper status modified effects. exposure: Copper 0.42 versus 5.74 micrograms/g diet; iron 38 versus 191 micrograms/g; ascorbate 0 versus 1%, for 20 days evidence_span: {"source_cache": "artifacts/copper-research/3337044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc", "start_char": 0, "end_char": 882, "text_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc"} [copper-p3337044] Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3337044/ DOI: 10.1093/ajcn/47.1.96
Complete structured claim and evidence
High iron together with dietary ascorbate aggravated anemia in copper-deficient rats.
L-Ascorbic acid → Anemia in copper-deficient rats source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/3337044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc", "start_char": 0, "end_char": 882, "text_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc"}
experimental_model
Factorial dietary copper, iron and ascorbate feeding experiment
exposure
Copper 0.42 versus 5.74 micrograms/g diet; iron 38 versus 191 micrograms/g; ascorbate 0 versus 1%, for 20 days
limitations
Animal feed concentrations cannot be converted into a human supplement rule. Baseline copper status modified effects.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Rat
plain_language
A nutrient combination worsened the deficit in this animal setting.
primary_references
[copper-p3337044] Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3337044/ DOI: 10.1093/ajcn/47.1.96
tissue_or_cell_type
Intestinal uptake, blood and tissues
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1157–1168
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Factorial dietary copper, iron and ascorbate feeding experiment · source_derived_draft · unverified_draft
### copper-iron-vitc-lowcu-anemia High iron together with dietary ascorbate aggravated anemia in copper-deficient rats. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A nutrient combination worsened the deficit in this animal setting. organism: Rat tissue_or_cell_type: Intestinal uptake, blood and tissues experimental_model: Factorial dietary copper, iron and ascorbate feeding experiment limitations: Animal feed concentrations cannot be converted into a human supplement rule. Baseline copper status modified effects. exposure: Copper 0.42 versus 5.74 micrograms/g diet; iron 38 versus 191 micrograms/g; ascorbate 0 versus 1%, for 20 days evidence_span: {"source_cache": "artifacts/copper-research/3337044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc", "start_char": 0, "end_char": 882, "text_sha256": "2302118b1dad186fdee87512abf58f47a36d430e329057c87b24e57e52e331cc"} [copper-p3337044] Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats. (1988). https://pubmed.ncbi.nlm.nih.gov/3337044/ DOI: 10.1093/ajcn/47.1.96
Complete structured claim and evidence
Adding iron to the zinc intervention prevented adverse iron-status changes but did not prevent the fall in erythrocyte Cu/Zn-SOD activity.
Iron → Erythrocyte copper/zinc superoxide dismutase activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/2912000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "start_char": 0, "end_char": 969, "text_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443"}
experimental_model
Zinc versus zinc-plus-iron intervention
exposure
50 mg/day zinc with or without 50 mg/day iron for ten weeks
limitations
Study exposures, not dosing recommendations; erythrocyte enzyme activity and ceruloplasmin concentration are distinct endpoints.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human adult females
plain_language
Correcting the iron side of an interaction did not correct the copper-related enzyme endpoint.
primary_references
[copper-p2912000] 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
Erythrocytes and serum
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1170–1181
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Zinc versus zinc-plus-iron intervention · source_derived_draft · unverified_draft
### copper-iron-does-not-prevent-zinc-sod-fall Adding iron to the zinc intervention prevented adverse iron-status changes but did not prevent the fall in erythrocyte Cu/Zn-SOD activity. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the iron side of an interaction did not correct the copper-related enzyme endpoint. organism: Human adult females tissue_or_cell_type: Erythrocytes and serum experimental_model: Zinc versus zinc-plus-iron intervention limitations: Study exposures, not dosing recommendations; erythrocyte enzyme activity and ceruloplasmin concentration are distinct endpoints. exposure: 50 mg/day zinc with or without 50 mg/day iron for ten weeks evidence_span: {"source_cache": "artifacts/copper-research/2912000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443", "start_char": 0, "end_char": 969, "text_sha256": "e2d70d43dded75edb026cac237f238d9e59399db6094098796e169f20e819443"} [copper-p2912000] 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
High copper intake in nine men produced small decreases in plasma homocysteine and folate, without changes in B12 or PLP measures.
Copper → Homocysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/15325682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a", "start_char": 0, "end_char": 1606, "text_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a"}
experimental_model
Long-duration high-copper feeding study
exposure
Nine men; prolonged high copper intake including 7 mg/day supplementation phase
limitations
Small intervention with biomarker outcomes; it does not establish copper as a human methionine-synthase cofactor, B-vitamin depletion, or benefit from high copper intake.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human young men
plain_language
Several vitamin-related blood markers shifted, but that does not identify a new copper-dependent methylation enzyme.
primary_references
[copper-p15325682] Effect of long-term, high-copper intake on the concentrations of plasma homocysteine and B vitamins in young men. (2004). https://pubmed.ncbi.nlm.nih.gov/15325682/ DOI: 10.1016/j.nut.2004.05.011
tissue_or_cell_type
Plasma homocysteine, folate, B12 and PLP
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1183–1194
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Long-duration high-copper feeding study · source_derived_draft · unverified_draft
### copper-copper-homocysteine-folate High copper intake in nine men produced small decreases in plasma homocysteine and folate, without changes in B12 or PLP measures. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several vitamin-related blood markers shifted, but that does not identify a new copper-dependent methylation enzyme. organism: Human young men tissue_or_cell_type: Plasma homocysteine, folate, B12 and PLP experimental_model: Long-duration high-copper feeding study limitations: Small intervention with biomarker outcomes; it does not establish copper as a human methionine-synthase cofactor, B-vitamin depletion, or benefit from high copper intake. exposure: Nine men; prolonged high copper intake including 7 mg/day supplementation phase evidence_span: {"source_cache": "artifacts/copper-research/15325682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a", "start_char": 0, "end_char": 1606, "text_sha256": "4b6a41a9645d006de2098c2ca83f5aaeab2f1d4d76608b1131dc47d0e2e4148a"} [copper-p15325682] Effect of long-term, high-copper intake on the concentrations of plasma homocysteine and B vitamins in young men. (2004). https://pubmed.ncbi.nlm.nih.gov/15325682/ DOI: 10.1016/j.nut.2004.05.011
Complete structured claim and evidence
Copper inhibited mouse PDE3B activity in the biochemical and adipocyte study.
Copper → Mouse cGMP-inhibited phosphodiesterase Pde3b source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/27272565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7", "start_char": 0, "end_char": 1018, "text_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7"}
experimental_model
Copper manipulation, purified Pde3b assays and adipocyte signaling
exposure
Copper perturbation and Pde3b cysteine mutations
limitations
This cellular signaling result is not a human weight-loss trial. Copper toxicity and systemic distribution are not captured by increasing one cell-culture signal.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse proteins and 3T3-L1 adipocytes; Atp7b mutant mouse context
plain_language
Copper slowed an enzyme that normally clears the cAMP signal.
primary_references
[copper-p27272565] Copper regulates cyclic-AMP-dependent lipolysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27272565/ DOI: 10.1038/nchembio.2098
tissue_or_cell_type
Adipocytes and purified enzyme
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1196–1207
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper manipulation, purified Pde3b assays and adipocyte signaling · source_derived_draft · unverified_draft
### copper-copper-pde3b Copper inhibited mouse PDE3B activity in the biochemical and adipocyte study. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper slowed an enzyme that normally clears the cAMP signal. organism: Mouse proteins and 3T3-L1 adipocytes; Atp7b mutant mouse context tissue_or_cell_type: Adipocytes and purified enzyme experimental_model: Copper manipulation, purified Pde3b assays and adipocyte signaling limitations: This cellular signaling result is not a human weight-loss trial. Copper toxicity and systemic distribution are not captured by increasing one cell-culture signal. exposure: Copper perturbation and Pde3b cysteine mutations evidence_span: {"source_cache": "artifacts/copper-research/27272565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7", "start_char": 0, "end_char": 1018, "text_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7"} [copper-p27272565] Copper regulates cyclic-AMP-dependent lipolysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27272565/ DOI: 10.1038/nchembio.2098
Complete structured claim and evidence
Copper-dependent PDE3B inhibition increased cAMP signaling and promoted lipolysis in 3T3-L1 adipocytes.
Mouse cGMP-inhibited phosphodiesterase Pde3b → Mouse adipocyte lipolysis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/27272565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7", "start_char": 0, "end_char": 1018, "text_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7"}
experimental_model
Copper manipulation, purified Pde3b assays and adipocyte signaling
exposure
Copper perturbation and Pde3b cysteine mutations
limitations
This cellular signaling result is not a human weight-loss trial. Copper toxicity and systemic distribution are not captured by increasing one cell-culture signal.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse proteins and 3T3-L1 adipocytes; Atp7b mutant mouse context
plain_language
The prolonged signal encouraged fat breakdown in these cells.
primary_references
[copper-p27272565] Copper regulates cyclic-AMP-dependent lipolysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27272565/ DOI: 10.1038/nchembio.2098
tissue_or_cell_type
Adipocytes and purified enzyme
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1209–1220
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper manipulation, purified Pde3b assays and adipocyte signaling · source_derived_draft · unverified_draft
### copper-pde3b-camp-lipolysis Copper-dependent PDE3B inhibition increased cAMP signaling and promoted lipolysis in 3T3-L1 adipocytes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The prolonged signal encouraged fat breakdown in these cells. organism: Mouse proteins and 3T3-L1 adipocytes; Atp7b mutant mouse context tissue_or_cell_type: Adipocytes and purified enzyme experimental_model: Copper manipulation, purified Pde3b assays and adipocyte signaling limitations: This cellular signaling result is not a human weight-loss trial. Copper toxicity and systemic distribution are not captured by increasing one cell-culture signal. exposure: Copper perturbation and Pde3b cysteine mutations evidence_span: {"source_cache": "artifacts/copper-research/27272565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7", "start_char": 0, "end_char": 1018, "text_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7"} [copper-p27272565] Copper regulates cyclic-AMP-dependent lipolysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27272565/ DOI: 10.1038/nchembio.2098
Complete structured claim and evidence
MEK1 mutations disrupting copper binding reduced BRAF V600E-driven signaling in the tested human and mouse systems.
Human mitogen-activated protein kinase kinase 1 / MEK1 / MAP2K1 → MEK-ERK MAPK pathway signaling source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/24717435.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef", "start_char": 0, "end_char": 1471, "text_sha256": "4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef"}
experimental_model
Copper-binding MEK1 mutants, CTR1 perturbation and tumor models
exposure
CTR1 reduction, MEK1 copper-binding disruption and chelation
limitations
Preclinical mechanism; does not establish dietary copper as a cancer cause or copper restriction as a treatment.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human and mouse experimental systems
plain_language
Copper binding influenced an enzyme in a growth-signaling chain.
primary_references
[copper-p24717435] Copper is required for oncogenic BRAF signalling and tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24717435/ DOI: 10.1038/nature13180
tissue_or_cell_type
BRAF V600E-driven signaling and tumor models
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1222–1233
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper-binding MEK1 mutants, CTR1 perturbation and tumor models · source_derived_draft · unverified_draft
### copper-cu-mek1-signaling MEK1 mutations disrupting copper binding reduced BRAF V600E-driven signaling in the tested human and mouse systems. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper binding influenced an enzyme in a growth-signaling chain. organism: Human and mouse experimental systems tissue_or_cell_type: BRAF V600E-driven signaling and tumor models experimental_model: Copper-binding MEK1 mutants, CTR1 perturbation and tumor models limitations: Preclinical mechanism; does not establish dietary copper as a cancer cause or copper restriction as a treatment. exposure: CTR1 reduction, MEK1 copper-binding disruption and chelation evidence_span: {"source_cache": "artifacts/copper-research/24717435.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef", "start_char": 0, "end_char": 1471, "text_sha256": "4eee319f693bd307d3930073167395e5ef454f07d976ca834539b637ec4406ef"} [copper-p24717435] Copper is required for oncogenic BRAF signalling and tumorigenesis. (2014). https://pubmed.ncbi.nlm.nih.gov/24717435/ DOI: 10.1038/nature13180
Complete structured claim and evidence
Direct copper interaction supported ULK1 kinase activity in the experimental system.
Copper → Human unc-51-like autophagy activating kinase ULK1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"}
experimental_model
Recombinant kinase assays, genetic perturbations and lung tumor models
exposure
Copper exposure, copper-binding mutations and Ctr1 deletion
limitations
Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human recombinant ULK1/ULK2 with complementary mouse systems
plain_language
Copper helps regulate one enzyme that starts cellular recycling.
primary_references
[copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
tissue_or_cell_type
Autophagy signaling
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1235–1246
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant kinase assays, genetic perturbations and lung tumor models · source_derived_draft · unverified_draft
### copper-cu-ulk1 Direct copper interaction supported ULK1 kinase activity in the experimental system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper helps regulate one enzyme that starts cellular recycling. organism: Human recombinant ULK1/ULK2 with complementary mouse systems tissue_or_cell_type: Autophagy signaling experimental_model: Recombinant kinase assays, genetic perturbations and lung tumor models limitations: Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival. exposure: Copper exposure, copper-binding mutations and Ctr1 deletion evidence_span: {"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"} [copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
Complete structured claim and evidence
Direct copper interaction also supported ULK2 kinase activity.
Copper → Human unc-51-like autophagy activating kinase ULK2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"}
experimental_model
Recombinant kinase assays, genetic perturbations and lung tumor models
exposure
Copper exposure, copper-binding mutations and Ctr1 deletion
limitations
Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human recombinant ULK1/ULK2 with complementary mouse systems
plain_language
The related recycling enzyme has a separately recorded copper interaction.
primary_references
[copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
tissue_or_cell_type
Autophagy signaling
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1248–1259
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant kinase assays, genetic perturbations and lung tumor models · source_derived_draft · unverified_draft
### copper-cu-ulk2 Direct copper interaction also supported ULK2 kinase activity. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The related recycling enzyme has a separately recorded copper interaction. organism: Human recombinant ULK1/ULK2 with complementary mouse systems tissue_or_cell_type: Autophagy signaling experimental_model: Recombinant kinase assays, genetic perturbations and lung tumor models limitations: Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival. exposure: Copper exposure, copper-binding mutations and Ctr1 deletion evidence_span: {"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"} [copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
Complete structured claim and evidence
Copper-binding-disruptive ULK1 mutations reduced autophagy signaling and autophagosome formation in the tested cells.
Human unc-51-like autophagy activating kinase ULK1 → Autophagosome formation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"}
experimental_model
Recombinant kinase assays, genetic perturbations and lung tumor models
exposure
Copper exposure, copper-binding mutations and Ctr1 deletion
limitations
Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human recombinant ULK1/ULK2 with complementary mouse systems
plain_language
A binding defect interrupted the recycling pathway downstream.
primary_references
[copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
tissue_or_cell_type
Autophagy signaling
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1261–1272
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant kinase assays, genetic perturbations and lung tumor models · source_derived_draft · unverified_draft
### copper-ulk1-copper-autophagy Copper-binding-disruptive ULK1 mutations reduced autophagy signaling and autophagosome formation in the tested cells. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A binding defect interrupted the recycling pathway downstream. organism: Human recombinant ULK1/ULK2 with complementary mouse systems tissue_or_cell_type: Autophagy signaling experimental_model: Recombinant kinase assays, genetic perturbations and lung tumor models limitations: Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival. exposure: Copper exposure, copper-binding mutations and Ctr1 deletion evidence_span: {"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"} [copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
Complete structured claim and evidence
CuCl2 treatment induced SLC7A11 expression in human MDA-MB-231 cells.
Copper(II) ion → Copper-exposure-induced SLC7A11 expression in human MDA-MB-231 cells source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"}
experimental_model
Copper and iron exposure with transcription-factor knockdown
exposure
CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown
limitations
One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human MDA-MB-231 breast cancer cells
plain_language
Copper exposure changed part of the cystine-entry system in these cells.
primary_references
[copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
tissue_or_cell_type
Cellular amino-acid transport machinery
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1274–1285
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper and iron exposure with transcription-factor knockdown · source_derived_draft · unverified_draft
### copper-cu-slc7a11 CuCl2 treatment induced SLC7A11 expression in human MDA-MB-231 cells. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper exposure changed part of the cystine-entry system in these cells. organism: Human MDA-MB-231 breast cancer cells tissue_or_cell_type: Cellular amino-acid transport machinery experimental_model: Copper and iron exposure with transcription-factor knockdown limitations: One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction. exposure: CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown evidence_span: {"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"} [copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
Complete structured claim and evidence
CuCl2 exposure promoted NRF2 nuclear translocation in the tested cancer cells.
Copper(II) ion → NRF2 nuclear translocation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"}
experimental_model
Copper and iron exposure with transcription-factor knockdown
exposure
CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown
limitations
One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human MDA-MB-231 breast cancer cells
plain_language
A stress-response regulator moved to the cell’s DNA-containing compartment.
primary_references
[copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
tissue_or_cell_type
Cellular amino-acid transport machinery
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1287–1298
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper and iron exposure with transcription-factor knockdown · source_derived_draft · unverified_draft
### copper-cu-nrf2 CuCl2 exposure promoted NRF2 nuclear translocation in the tested cancer cells. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stress-response regulator moved to the cell’s DNA-containing compartment. organism: Human MDA-MB-231 breast cancer cells tissue_or_cell_type: Cellular amino-acid transport machinery experimental_model: Copper and iron exposure with transcription-factor knockdown limitations: One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction. exposure: CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown evidence_span: {"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"} [copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
Complete structured claim and evidence
NRF2 knockdown suppressed copper-induced SLC7A11 expression.
Human Nrf2 / NFE2L2 → Copper-exposure-induced SLC7A11 expression in human MDA-MB-231 cells source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"}
experimental_model
Copper and iron exposure with transcription-factor knockdown
exposure
CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown
limitations
One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human MDA-MB-231 breast cancer cells
plain_language
The stress-response regulator was part of the transporter-expression response.
primary_references
[copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
tissue_or_cell_type
Cellular amino-acid transport machinery
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1300–1311
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper and iron exposure with transcription-factor knockdown · source_derived_draft · unverified_draft
### copper-nrf2-slc7a11 NRF2 knockdown suppressed copper-induced SLC7A11 expression. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The stress-response regulator was part of the transporter-expression response. organism: Human MDA-MB-231 breast cancer cells tissue_or_cell_type: Cellular amino-acid transport machinery experimental_model: Copper and iron exposure with transcription-factor knockdown limitations: One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction. exposure: CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown evidence_span: {"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"} [copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
Complete structured claim and evidence
ATOX1 knockdown also impaired copper-induced SLC7A11 expression.
Human copper chaperone ATOX1 → Copper-exposure-induced SLC7A11 expression in human MDA-MB-231 cells source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"}
experimental_model
Copper and iron exposure with transcription-factor knockdown
exposure
CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown
limitations
One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human MDA-MB-231 breast cancer cells
plain_language
A copper-handling protein participated in this gene-expression response.
primary_references
[copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
tissue_or_cell_type
Cellular amino-acid transport machinery
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1313–1324
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper and iron exposure with transcription-factor knockdown · source_derived_draft · unverified_draft
### copper-atox1-slc7a11 ATOX1 knockdown also impaired copper-induced SLC7A11 expression. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper-handling protein participated in this gene-expression response. organism: Human MDA-MB-231 breast cancer cells tissue_or_cell_type: Cellular amino-acid transport machinery experimental_model: Copper and iron exposure with transcription-factor knockdown limitations: One cancer-cell model. Expression changes do not prove increased glutathione synthesis, tumor progression, or a clinical nutrient interaction. exposure: CuCl2 or FeCl2 exposure; NFE2L2 or ATOX1 knockdown evidence_span: {"source_cache": "artifacts/copper-research/40944334.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89", "start_char": 0, "end_char": 1634, "text_sha256": "6df1716e8998546d22a1d96116e1bc35b1f7e24c94868ec5e441ada6a2be3e89"} [copper-p40944334] Copper induces cystine/glutamate antiporter SLC7A11 through the activation of Nrf2 and Atox1 pathways. (2025). https://pubmed.ncbi.nlm.nih.gov/40944334/ DOI: 10.1080/10715762.2025.2560847
Complete structured claim and evidence
The low-copper period reduced plasma copper in the eleven-man metabolic-ward study.
Copper → Plasma copper concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/8988916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b", "start_char": 0, "end_char": 1349, "text_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b"}
experimental_model
Metabolic-ward depletion and repletion study
exposure
Eleven men: 0.66 mg copper/day for 24 days, 0.38 for 42 days, then 2.49 for 24 days
limitations
Small controlled feeding study; regimen-specific changes are not universal diagnostic thresholds or modern intake recommendations.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human young men
plain_language
Sustained low intake changed the circulating copper measurement.
primary_references
[copper-p8988916] Copper status of young men consuming a low-copper diet. (1997). https://pubmed.ncbi.nlm.nih.gov/8988916/ DOI: 10.1093/ajcn/65.1.72
tissue_or_cell_type
Plasma, urine and erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1326–1337
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-ward depletion and repletion study · source_derived_draft · unverified_draft
### copper-human-lowcu-plasma The low-copper period reduced plasma copper in the eleven-man metabolic-ward study. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sustained low intake changed the circulating copper measurement. organism: Human young men tissue_or_cell_type: Plasma, urine and erythrocytes experimental_model: Metabolic-ward depletion and repletion study limitations: Small controlled feeding study; regimen-specific changes are not universal diagnostic thresholds or modern intake recommendations. exposure: Eleven men: 0.66 mg copper/day for 24 days, 0.38 for 42 days, then 2.49 for 24 days evidence_span: {"source_cache": "artifacts/copper-research/8988916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b", "start_char": 0, "end_char": 1349, "text_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b"} [copper-p8988916] Copper status of young men consuming a low-copper diet. (1997). https://pubmed.ncbi.nlm.nih.gov/8988916/ DOI: 10.1093/ajcn/65.1.72
Complete structured claim and evidence
Low copper intake reduced ceruloplasmin activity and protein concentration; repletion raised plasma copper and ceruloplasmin protein.
Copper → Circulating ceruloplasmin oxidase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/8988916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b", "start_char": 0, "end_char": 1349, "text_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b"}
experimental_model
Metabolic-ward depletion and repletion study
exposure
Eleven men: 0.66 mg copper/day for 24 days, 0.38 for 42 days, then 2.49 for 24 days
limitations
Small controlled feeding study; regimen-specific changes are not universal diagnostic thresholds or modern intake recommendations.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human young men
plain_language
Both enzyme activity and its amount responded to copper supply.
primary_references
[copper-p8988916] Copper status of young men consuming a low-copper diet. (1997). https://pubmed.ncbi.nlm.nih.gov/8988916/ DOI: 10.1093/ajcn/65.1.72
tissue_or_cell_type
Plasma, urine and erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1339–1350
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-ward depletion and repletion study · source_derived_draft · unverified_draft
### copper-human-lowcu-cp Low copper intake reduced ceruloplasmin activity and protein concentration; repletion raised plasma copper and ceruloplasmin protein. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both enzyme activity and its amount responded to copper supply. organism: Human young men tissue_or_cell_type: Plasma, urine and erythrocytes experimental_model: Metabolic-ward depletion and repletion study limitations: Small controlled feeding study; regimen-specific changes are not universal diagnostic thresholds or modern intake recommendations. exposure: Eleven men: 0.66 mg copper/day for 24 days, 0.38 for 42 days, then 2.49 for 24 days evidence_span: {"source_cache": "artifacts/copper-research/8988916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b", "start_char": 0, "end_char": 1349, "text_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b"} [copper-p8988916] Copper status of young men consuming a low-copper diet. (1997). https://pubmed.ncbi.nlm.nih.gov/8988916/ DOI: 10.1093/ajcn/65.1.72
Complete structured claim and evidence
Erythrocyte SOD activity was lower on average during low intake, but did not show a significant time trend across depletion.
Copper → Erythrocyte copper/zinc superoxide dismutase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/8988916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b", "start_char": 0, "end_char": 1349, "text_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b"}
experimental_model
Metabolic-ward depletion and repletion study
exposure
Eleven men: 0.66 mg copper/day for 24 days, 0.38 for 42 days, then 2.49 for 24 days
limitations
Small controlled feeding study; regimen-specific changes are not universal diagnostic thresholds or modern intake recommendations.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human young men
plain_language
Not every copper-related marker responded with the same sensitivity.
primary_references
[copper-p8988916] Copper status of young men consuming a low-copper diet. (1997). https://pubmed.ncbi.nlm.nih.gov/8988916/ DOI: 10.1093/ajcn/65.1.72
tissue_or_cell_type
Plasma, urine and erythrocytes
trigger_kind
biomarker_context Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1352–1363
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-ward depletion and repletion study · source_derived_draft · unverified_draft
### copper-human-lowcu-sod-boundary Erythrocyte SOD activity was lower on average during low intake, but did not show a significant time trend across depletion. Condition category: biomarker_context nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every copper-related marker responded with the same sensitivity. organism: Human young men tissue_or_cell_type: Plasma, urine and erythrocytes experimental_model: Metabolic-ward depletion and repletion study limitations: Small controlled feeding study; regimen-specific changes are not universal diagnostic thresholds or modern intake recommendations. exposure: Eleven men: 0.66 mg copper/day for 24 days, 0.38 for 42 days, then 2.49 for 24 days evidence_span: {"source_cache": "artifacts/copper-research/8988916.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b", "start_char": 0, "end_char": 1349, "text_sha256": "0be30b28f91bce964b969517de4b15eb3ba5905a6f5f1f0a9dc4afa29e9d101b"} [copper-p8988916] Copper status of young men consuming a low-copper diet. (1997). https://pubmed.ncbi.nlm.nih.gov/8988916/ DOI: 10.1093/ajcn/65.1.72
Complete structured claim and evidence
Endogenous copper losses increased from about 0.45 to 0.81 to 2.46 mg/day across the low, medium and high copper-intake conditions.
Copper → Endogenous copper excretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/12844388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def", "start_char": 0, "end_char": 1336, "text_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def"}
experimental_model
Controlled copper intake and stable-isotope balance study
exposure
Twelve men; 0.7, 1.6 or 6 mg/day intake periods with an oral 3 mg isotope challenge
limitations
The isotope challenge was the same at each dietary background. Similar fractional absorption under this test does not mean copper absorption is invariant at every dose.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human men
plain_language
The body adjusted how much copper it removed.
primary_references
[copper-p12844388] Adaptive responses in men fed low- and high-copper diets. (2003). https://pubmed.ncbi.nlm.nih.gov/12844388/ DOI: 10.1079/bjn2003887
tissue_or_cell_type
Whole-body copper handling
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1365–1376
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled copper intake and stable-isotope balance study · source_derived_draft · unverified_draft
### copper-copper-excretion-adaptation Endogenous copper losses increased from about 0.45 to 0.81 to 2.46 mg/day across the low, medium and high copper-intake conditions. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The body adjusted how much copper it removed. organism: Human men tissue_or_cell_type: Whole-body copper handling experimental_model: Controlled copper intake and stable-isotope balance study limitations: The isotope challenge was the same at each dietary background. Similar fractional absorption under this test does not mean copper absorption is invariant at every dose. exposure: Twelve men; 0.7, 1.6 or 6 mg/day intake periods with an oral 3 mg isotope challenge evidence_span: {"source_cache": "artifacts/copper-research/12844388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def", "start_char": 0, "end_char": 1336, "text_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def"} [copper-p12844388] Adaptive responses in men fed low- and high-copper diets. (2003). https://pubmed.ncbi.nlm.nih.gov/12844388/ DOI: 10.1079/bjn2003887
Complete structured claim and evidence
True fractional copper absorption after the standardized tracer dose was about 48% at both low and high background intakes, without a significant difference.
Copper → Intestinal copper absorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/12844388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def", "start_char": 0, "end_char": 1336, "text_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def"}
experimental_model
Controlled copper intake and stable-isotope balance study
exposure
Twelve men; 0.7, 1.6 or 6 mg/day intake periods with an oral 3 mg isotope challenge
limitations
The isotope challenge was the same at each dietary background. Similar fractional absorption under this test does not mean copper absorption is invariant at every dose.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human men
plain_language
In this experiment, excretion changed more clearly than the measured absorption fraction.
primary_references
[copper-p12844388] Adaptive responses in men fed low- and high-copper diets. (2003). https://pubmed.ncbi.nlm.nih.gov/12844388/ DOI: 10.1079/bjn2003887
tissue_or_cell_type
Whole-body copper handling
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1378–1389
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled copper intake and stable-isotope balance study · source_derived_draft · unverified_draft
### copper-copper-absorption-adaptation True fractional copper absorption after the standardized tracer dose was about 48% at both low and high background intakes, without a significant difference. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this experiment, excretion changed more clearly than the measured absorption fraction. organism: Human men tissue_or_cell_type: Whole-body copper handling experimental_model: Controlled copper intake and stable-isotope balance study limitations: The isotope challenge was the same at each dietary background. Similar fractional absorption under this test does not mean copper absorption is invariant at every dose. exposure: Twelve men; 0.7, 1.6 or 6 mg/day intake periods with an oral 3 mg isotope challenge evidence_span: {"source_cache": "artifacts/copper-research/12844388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def", "start_char": 0, "end_char": 1336, "text_sha256": "5b6c40ba96ca6bba0b6d377caf643f3aebba366919c889e2e8f10be4b23a0def"} [copper-p12844388] Adaptive responses in men fed low- and high-copper diets. (2003). https://pubmed.ncbi.nlm.nih.gov/12844388/ DOI: 10.1079/bjn2003887
Complete structured claim and evidence
Copper deficiency was identified in 13 of 136 clinic patients after Roux-en-Y gastric bypass; many had anemia, leukopenia or neuromuscular abnormalities.
Roux-en-Y gastric bypass → Biochemically low copper status source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/21876546.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8", "start_char": 0, "end_char": 1842, "text_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8"}
experimental_model
Post-Roux-en-Y clinic cohort and longitudinal subset
exposure
136-person clinic cohort; separate longitudinal group of sixteen
limitations
The study observed postoperative deficiency; it did not directly quantify copper absorption in these participants. The 9.6% prevalence is specific to this clinic cohort.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
After this surgery, some patients developed a clinically important copper shortage.
primary_references
[copper-p21876546] Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery. (2012). https://pubmed.ncbi.nlm.nih.gov/21876546/ DOI: 10.1038/ijo.2011.159
tissue_or_cell_type
Blood and clinical findings after gastric bypass
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1391–1402
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Post-Roux-en-Y clinic cohort and longitudinal subset · source_derived_draft · unverified_draft
### copper-bypass-lowcu Copper deficiency was identified in 13 of 136 clinic patients after Roux-en-Y gastric bypass; many had anemia, leukopenia or neuromuscular abnormalities. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: After this surgery, some patients developed a clinically important copper shortage. organism: Human tissue_or_cell_type: Blood and clinical findings after gastric bypass experimental_model: Post-Roux-en-Y clinic cohort and longitudinal subset limitations: The study observed postoperative deficiency; it did not directly quantify copper absorption in these participants. The 9.6% prevalence is specific to this clinic cohort. exposure: 136-person clinic cohort; separate longitudinal group of sixteen evidence_span: {"source_cache": "artifacts/copper-research/21876546.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8", "start_char": 0, "end_char": 1842, "text_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8"} [copper-p21876546] Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery. (2012). https://pubmed.ncbi.nlm.nih.gov/21876546/ DOI: 10.1038/ijo.2011.159
Complete structured claim and evidence
In the sixteen-person longitudinal group, plasma copper and ceruloplasmin declined over follow-up, with a reported copper-deficiency incidence of 18.8%.
Biochemically low copper status → Serum ceruloplasmin concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/21876546.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8", "start_char": 0, "end_char": 1842, "text_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8"}
experimental_model
Post-Roux-en-Y clinic cohort and longitudinal subset
exposure
136-person clinic cohort; separate longitudinal group of sixteen
limitations
Clinic selection and small longitudinal sample limit generalization; the study does not establish the sole molecular cause of every postoperative symptom.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
Following the same people over time detected falling copper-related measures.
primary_references
[copper-p21876546] Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery. (2012). https://pubmed.ncbi.nlm.nih.gov/21876546/ DOI: 10.1038/ijo.2011.159
tissue_or_cell_type
Blood and clinical findings after gastric bypass
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1404–1415
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Post-Roux-en-Y clinic cohort and longitudinal subset · source_derived_draft · unverified_draft
### copper-bypass-cp-timecourse In the sixteen-person longitudinal group, plasma copper and ceruloplasmin declined over follow-up, with a reported copper-deficiency incidence of 18.8%. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Following the same people over time detected falling copper-related measures. organism: Human tissue_or_cell_type: Blood and clinical findings after gastric bypass experimental_model: Post-Roux-en-Y clinic cohort and longitudinal subset limitations: Clinic selection and small longitudinal sample limit generalization; the study does not establish the sole molecular cause of every postoperative symptom. exposure: 136-person clinic cohort; separate longitudinal group of sixteen evidence_span: {"source_cache": "artifacts/copper-research/21876546.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8", "start_char": 0, "end_char": 1842, "text_sha256": "29b1cc8c0170160c3a7b3449d807bbf309f6e1fa230e453fbfa467fe23fa71c8"} [copper-p21876546] Incidence and prevalence of copper deficiency following roux-en-y gastric bypass surgery. (2012). https://pubmed.ncbi.nlm.nih.gov/21876546/ DOI: 10.1038/ijo.2011.159
Complete structured claim and evidence
All six patients had prominent gait impairment from sensory ataxia.
Myeloneuropathy associated with copper deficiency → Sensory ataxia source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/18495738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644", "start_char": 0, "end_char": 1153, "text_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644"}
experimental_model
Clinical neurophysiology case series
exposure
Six patients with copper-deficiency myeloneuropathy
limitations
Small case series; does not identify one causal cuproenzyme or establish that B12 deficiency caused the syndrome.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
Loss of position-sense signaling can make walking unstable.
primary_references
[copper-p18495738] Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. (2009). https://pubmed.ncbi.nlm.nih.gov/18495738/ DOI: 10.1136/jnnp.2008.144683
tissue_or_cell_type
Peripheral and central sensory pathways
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1417–1428
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical neurophysiology case series · source_derived_draft · unverified_draft
### copper-cud-sensory-ataxia All six patients had prominent gait impairment from sensory ataxia. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of position-sense signaling can make walking unstable. organism: Human tissue_or_cell_type: Peripheral and central sensory pathways experimental_model: Clinical neurophysiology case series limitations: Small case series; does not identify one causal cuproenzyme or establish that B12 deficiency caused the syndrome. exposure: Six patients with copper-deficiency myeloneuropathy evidence_span: {"source_cache": "artifacts/copper-research/18495738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644", "start_char": 0, "end_char": 1153, "text_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644"} [copper-p18495738] Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. (2009). https://pubmed.ncbi.nlm.nih.gov/18495738/ DOI: 10.1136/jnnp.2008.144683
Complete structured claim and evidence
Neurophysiology showed distal axonal sensorimotor neuropathy; all five tested with somatosensory evoked potentials also had central or proximal pathway abnormalities.
Myeloneuropathy associated with copper deficiency → Axonal sensorimotor peripheral neuropathy source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/18495738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644", "start_char": 0, "end_char": 1153, "text_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644"}
experimental_model
Clinical neurophysiology case series
exposure
Six patients with copper-deficiency myeloneuropathy
limitations
Small case series; does not identify one causal cuproenzyme or establish that B12 deficiency caused the syndrome.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human
plain_language
The impairment was not limited to one part of the nerve pathway.
primary_references
[copper-p18495738] Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. (2009). https://pubmed.ncbi.nlm.nih.gov/18495738/ DOI: 10.1136/jnnp.2008.144683
tissue_or_cell_type
Peripheral and central sensory pathways
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1430–1441
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical neurophysiology case series · source_derived_draft · unverified_draft
### copper-cud-axonal-neuropathy Neurophysiology showed distal axonal sensorimotor neuropathy; all five tested with somatosensory evoked potentials also had central or proximal pathway abnormalities. Condition category: nutrient_deficiency nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The impairment was not limited to one part of the nerve pathway. organism: Human tissue_or_cell_type: Peripheral and central sensory pathways experimental_model: Clinical neurophysiology case series limitations: Small case series; does not identify one causal cuproenzyme or establish that B12 deficiency caused the syndrome. exposure: Six patients with copper-deficiency myeloneuropathy evidence_span: {"source_cache": "artifacts/copper-research/18495738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644", "start_char": 0, "end_char": 1153, "text_sha256": "0869f1a2ef3e333451666857ce5f005a08028c0fec6b384dce5fa69b4ae15644"} [copper-p18495738] Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. (2009). https://pubmed.ncbi.nlm.nih.gov/18495738/ DOI: 10.1136/jnnp.2008.144683
Complete structured claim and evidence
Survival was 92% in the twelve early-treated infants at median 4.6-year follow-up versus 13% in the historical late-treatment group at median 1.8 years.
Copper → Survival following early copper treatment in Menkes disease source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/18256395.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce", "start_char": 0, "end_char": 2319, "text_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce"}
experimental_model
Early-treatment Menkes cohort with historical comparison and functional genotyping
exposure
Copper injections begun by 22 days in twelve infants; comparison with fifteen later-treated historical patients
limitations
Not randomized; survival follow-up differed between cohorts. Genotype and residual function influenced outcome, so results cannot be generalized to every ATP7A variant.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human infants
plain_language
Early treatment was associated with much better survival in this cohort, with important comparison limits.
primary_references
[copper-p18256395] Neonatal diagnosis and treatment of Menkes disease. (2008). https://pubmed.ncbi.nlm.nih.gov/18256395/ DOI: 10.1056/nejmoa070613
tissue_or_cell_type
Survival and neurodevelopment
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1443–1454
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Early-treatment Menkes cohort with historical comparison and functional genotyping · source_derived_draft · unverified_draft
### copper-menkes-early-survival Survival was 92% in the twelve early-treated infants at median 4.6-year follow-up versus 13% in the historical late-treatment group at median 1.8 years. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Early treatment was associated with much better survival in this cohort, with important comparison limits. organism: Human infants tissue_or_cell_type: Survival and neurodevelopment experimental_model: Early-treatment Menkes cohort with historical comparison and functional genotyping limitations: Not randomized; survival follow-up differed between cohorts. Genotype and residual function influenced outcome, so results cannot be generalized to every ATP7A variant. exposure: Copper injections begun by 22 days in twelve infants; comparison with fifteen later-treated historical patients evidence_span: {"source_cache": "artifacts/copper-research/18256395.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce", "start_char": 0, "end_char": 2319, "text_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce"} [copper-p18256395] Neonatal diagnosis and treatment of Menkes disease. (2008). https://pubmed.ncbi.nlm.nih.gov/18256395/ DOI: 10.1056/nejmoa070613
Complete structured claim and evidence
The two early-treated children with normal neurodevelopment and myelination had variants permitting residual ATP7A activity or some correctly spliced transcript.
Human copper-transporting ATPase ATP7A → Neurodevelopment following early copper treatment in Menkes disease source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/18256395.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce", "start_char": 0, "end_char": 2319, "text_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce"}
experimental_model
Early-treatment Menkes cohort with historical comparison and functional genotyping
exposure
Copper injections begun by 22 days in twelve infants; comparison with fifteen later-treated historical patients
limitations
Not randomized; survival follow-up differed between cohorts. Genotype and residual function influenced outcome, so results cannot be generalized to every ATP7A variant.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human infants
plain_language
Delivering copper early worked best when some transport machinery still functioned.
primary_references
[copper-p18256395] Neonatal diagnosis and treatment of Menkes disease. (2008). https://pubmed.ncbi.nlm.nih.gov/18256395/ DOI: 10.1056/nejmoa070613
tissue_or_cell_type
Survival and neurodevelopment
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1456–1467
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Early-treatment Menkes cohort with historical comparison and functional genotyping · source_derived_draft · unverified_draft
### copper-menkes-residual-function The two early-treated children with normal neurodevelopment and myelination had variants permitting residual ATP7A activity or some correctly spliced transcript. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Delivering copper early worked best when some transport machinery still functioned. organism: Human infants tissue_or_cell_type: Survival and neurodevelopment experimental_model: Early-treatment Menkes cohort with historical comparison and functional genotyping limitations: Not randomized; survival follow-up differed between cohorts. Genotype and residual function influenced outcome, so results cannot be generalized to every ATP7A variant. exposure: Copper injections begun by 22 days in twelve infants; comparison with fifteen later-treated historical patients evidence_span: {"source_cache": "artifacts/copper-research/18256395.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce", "start_char": 0, "end_char": 2319, "text_sha256": "e855a0286cb633432b654005d756aa1e887ddace4f2a4dc5fee6cca518d895ce"} [copper-p18256395] Neonatal diagnosis and treatment of Menkes disease. (2008). https://pubmed.ncbi.nlm.nih.gov/18256395/ DOI: 10.1056/nejmoa070613
Complete structured claim and evidence
Trientine tetrahydrochloride was noninferior to penicillamine for the specified non-ceruloplasmin copper endpoint at 24 weeks in stable adults with Wilson disease.
Trientine tetrahydrochloride → Copper control during maintenance treatment of Wilson disease source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/36183738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166", "start_char": 0, "end_char": 4337, "text_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166"}
experimental_model
Randomized open-label CHELATE maintenance noninferiority trial
exposure
Fifty-three adults previously stable on penicillamine for at least a year; trientine tetrahydrochloride versus penicillamine
limitations
Maintenance trial in stable adults, not initial treatment of severe disease. Noninferiority is not superiority and does not validate general detoxification.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human adults with stable Wilson disease
plain_language
A copper-binding treatment maintained control in this defined patient group.
primary_references
[copper-p36183738] Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36183738/ DOI: 10.1016/s2468-1253(22)00270-9
tissue_or_cell_type
Circulating non-ceruloplasmin copper and clinical stability
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1469–1480
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized open-label CHELATE maintenance noninferiority trial · source_derived_draft · unverified_draft
### copper-wilson-trientine-maintenance Trientine tetrahydrochloride was noninferior to penicillamine for the specified non-ceruloplasmin copper endpoint at 24 weeks in stable adults with Wilson disease. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A copper-binding treatment maintained control in this defined patient group. organism: Human adults with stable Wilson disease tissue_or_cell_type: Circulating non-ceruloplasmin copper and clinical stability experimental_model: Randomized open-label CHELATE maintenance noninferiority trial limitations: Maintenance trial in stable adults, not initial treatment of severe disease. Noninferiority is not superiority and does not validate general detoxification. exposure: Fifty-three adults previously stable on penicillamine for at least a year; trientine tetrahydrochloride versus penicillamine evidence_span: {"source_cache": "artifacts/copper-research/36183738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166", "start_char": 0, "end_char": 4337, "text_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166"} [copper-p36183738] Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36183738/ DOI: 10.1016/s2468-1253(22)00270-9
Complete structured claim and evidence
Urinary copper was lower with trientine tetrahydrochloride, while clinical stability was maintained in both trial groups.
Trientine tetrahydrochloride → Copper control during maintenance treatment of Wilson disease source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/copper-research/36183738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166", "start_char": 0, "end_char": 4337, "text_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166"}
experimental_model
Randomized open-label CHELATE maintenance noninferiority trial
exposure
Fifty-three adults previously stable on penicillamine for at least a year; trientine tetrahydrochloride versus penicillamine
limitations
Maintenance trial in stable adults, not initial treatment of severe disease. Noninferiority is not superiority and does not validate general detoxification.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human adults with stable Wilson disease
plain_language
Different copper measurements can coexist with similar clinical control.
primary_references
[copper-p36183738] Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36183738/ DOI: 10.1016/s2468-1253(22)00270-9
tissue_or_cell_type
Circulating non-ceruloplasmin copper and clinical stability
trigger_kind
machinery_impairment Imported condition classification; unverified.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1482–1493
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized open-label CHELATE maintenance noninferiority trial · source_derived_draft · unverified_draft
### copper-wilson-urine-clinical-boundary Urinary copper was lower with trientine tetrahydrochloride, while clinical stability was maintained in both trial groups. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different copper measurements can coexist with similar clinical control. organism: Human adults with stable Wilson disease tissue_or_cell_type: Circulating non-ceruloplasmin copper and clinical stability experimental_model: Randomized open-label CHELATE maintenance noninferiority trial limitations: Maintenance trial in stable adults, not initial treatment of severe disease. Noninferiority is not superiority and does not validate general detoxification. exposure: Fifty-three adults previously stable on penicillamine for at least a year; trientine tetrahydrochloride versus penicillamine evidence_span: {"source_cache": "artifacts/copper-research/36183738.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166", "start_char": 0, "end_char": 4337, "text_sha256": "6235ee4003a7016b645aca9e0df7ea34076b266ebecb33bb878ce75e2c052166"} [copper-p36183738] Trientine tetrahydrochloride versus penicillamine for maintenance therapy in Wilson disease (CHELATE): a randomised, open-label, non-inferiority, phase 3 trial. (2022). https://pubmed.ncbi.nlm.nih.gov/36183738/ DOI: 10.1016/s2468-1253(22)00270-9
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 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
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
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
Human SOD1 maturation involves copper and zinc insertion and a Cys57–Cys146 disulfide; this is a different metalloprotein system from manganese SOD2.
Human copper-zinc superoxide dismutase / SOD1 → SOD1 maturation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Copper and zinc cofactor identity in SOD1 is distinguished from Mn-dependent SOD2.
experimental_model
NMR of copper-depleted human SOD1 C6A/C111S preparation
exposure
Copper-depleted zinc-containing disulfide-reduced preparation
limitations
The study structurally examined the C6A/C111S copper-depleted, zinc-containing preparation. This identity statement does not assert Mn can replace either SOD1 metal.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
SOD1 and SOD2 use different metals.
primary_references
[mn-enz-16291742] Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form. (2006). https://pubmed.ncbi.nlm.nih.gov/16291742/ DOI: 10.1074/jbc.m506497200
tissue_or_cell_type
Purified SOD1
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 458–469
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NMR of copper-depleted human SOD1 C6A/C111S preparation · source_derived_draft · unverified_draft
### mn-enz-sod1-distinct-metals Human SOD1 maturation involves copper and zinc insertion and a Cys57–Cys146 disulfide; this is a different metalloprotein system from manganese SOD2. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD1 and SOD2 use different metals. organism: Homo sapiens protein tissue_or_cell_type: Purified SOD1 experimental_model: NMR of copper-depleted human SOD1 C6A/C111S preparation limitations: The study structurally examined the C6A/C111S copper-depleted, zinc-containing preparation. This identity statement does not assert Mn can replace either SOD1 metal. exposure: Copper-depleted zinc-containing disulfide-reduced preparation cross_nutrient: Copper and zinc cofactor identity in SOD1 is distinguished from Mn-dependent SOD2. [mn-enz-16291742] Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form. (2006). https://pubmed.ncbi.nlm.nih.gov/16291742/ DOI: 10.1074/jbc.m506497200
Complete structured claim and evidence
Dietary copper availability altered tendon lysyl-oxidase activation in the chick experiments.
Copper(II) ion → Lysyl oxidase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Chicks receiving diets differing in copper; tendon enzyme assays.
limitations
Copper manipulation in chicks, not evidence of dietary lysine deficiency or a human copper/lysine dose recommendation.
organism
Chicken
plain_language
Insufficient copper can limit a lysine-processing enzyme even when its substrate is present.
primary_references
[lox-copper-1999] Activation of chick tendon lysyl oxidase in response to dietary copper (1999). https://pubmed.ncbi.nlm.nih.gov/10573541/
tissue_or_cell_type
Tendon
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 497–505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chicks receiving diets differing in copper; tendon enzyme assays. · source_derived_draft · unverified_draft
### copper-insufficiency-lox Dietary copper availability altered tendon lysyl-oxidase activation in the chick experiments. Plain language: Insufficient copper can limit a lysine-processing enzyme even when its substrate is present. Condition category: nutrient_deficiency organism: Chicken tissue_or_cell_type: Tendon experimental_model: Chicks receiving diets differing in copper; tendon enzyme assays. limitations: Copper manipulation in chicks, not evidence of dietary lysine deficiency or a human copper/lysine dose recommendation. [lox-copper-1999] Activation of chick tendon lysyl oxidase in response to dietary copper (1999). https://pubmed.ncbi.nlm.nih.gov/10573541/
Complete structured claim and evidence
A protein-derived lysine-tyrosylquinone cofactor was identified in bovine aortic lysyl oxidase.
Protein-bound lysine tyrosylquinone → LOX source_derived_draftungraded
Experimental context and source evidence
experimental_model
Bovine aortic enzyme sequencing, mass spectrometry and spectroscopy.
limitations
This protein-bound cofactor is neither a vitamin nor free lysine, and the experiment did not test dietary supplementation.
organism
Cattle
plain_language
Two amino-acid side chains in the enzyme form part of its catalytic machinery.
primary_references
[lox-ltq-1996] A crosslinked cofactor in lysyl oxidase: redox function for amino acid side chains (1996). https://pubmed.ncbi.nlm.nih.gov/8688089/ DOI: 10.1126/science.273.5278.1078
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 487–495
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine aortic enzyme sequencing, mass spectrometry and spectroscopy. · source_derived_draft · unverified_draft
### lox-ltq-cofactor A protein-derived lysine-tyrosylquinone cofactor was identified in bovine aortic lysyl oxidase. Plain language: Two amino-acid side chains in the enzyme form part of its catalytic machinery. Condition category: normal organism: Cattle tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Bovine aortic enzyme sequencing, mass spectrometry and spectroscopy. limitations: This protein-bound cofactor is neither a vitamin nor free lysine, and the experiment did not test dietary supplementation. [lox-ltq-1996] A crosslinked cofactor in lysyl oxidase: redox function for amino acid side chains (1996). https://pubmed.ncbi.nlm.nih.gov/8688089/ DOI: 10.1126/science.273.5278.1078
Complete structured claim and evidence
Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide.
Lysyl oxidase enzyme family → Collagen/elastin peptidyl lysine substrates source_derived_draftungraded
Experimental context and source evidence
experimental_model
LOXL2 assay development and total-family activity detection in cultured cells and tissue.
limitations
Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury.
organism
Mammalian cells/tissues and recombinant LOXL2; see study methods
plain_language
An enzyme creates reactive attachment sites used in matrix cross-linking.
primary_references
[lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 467–475
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOXL2 assay development and total-family activity detection in cultured cells and tissue. · source_derived_draft · unverified_draft
### lox-peptidyl-lysine-oxidation Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide. Plain language: An enzyme creates reactive attachment sites used in matrix cross-linking. Condition category: normal organism: Mammalian cells/tissues and recombinant LOXL2; see study methods tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: LOXL2 assay development and total-family activity detection in cultured cells and tissue. limitations: Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury. [lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/
Complete structured claim and evidence
Pituitary peptide-amidating activity inhibited by divalent-metal chelators was restored above control by copper addition; the assayed reaction also required molecular oxygen.
Copper(II) ion → Bovine peptidylglycine alpha-amidating monooxygenase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Rat pituitary and bovine intermediate-pituitary secretory-granule preparations
exposure
Synthetic D-Tyr-Val-Gly amidation with varied ascorbate, oxygen and divalent-metal chelators/copper.
limitations
Study included rat and bovine preparations; this cofactor observation is scoped to those preparations rather than a human nutritional copper trial.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Rattus norvegicus; Bos taurus
plain_language
Vitamin C and copper participate together, and removing available metal stops this peptide-processing assay.
primary_references
[pam1983] Identification in pituitary tissue of a peptide alpha-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid. (1983). https://pubmed.ncbi.nlm.nih.gov/6576381/ DOI: 10.1073/pnas.80.16.5144
tissue_or_cell_type
Pituitary secretory granules
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 872–883
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat pituitary and bovine intermediate-pituitary secretory-granule preparations · source_derived_draft · unverified_draft
### vc-enzyme-amidation-copper-recovery Pituitary peptide-amidating activity inhibited by divalent-metal chelators was restored above control by copper addition; the assayed reaction also required molecular oxygen. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C and copper participate together, and removing available metal stops this peptide-processing assay. organism: Rattus norvegicus; Bos taurus tissue_or_cell_type: Pituitary secretory granules experimental_model: Rat pituitary and bovine intermediate-pituitary secretory-granule preparations limitations: Study included rat and bovine preparations; this cofactor observation is scoped to those preparations rather than a human nutritional copper trial. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Synthetic D-Tyr-Val-Gly amidation with varied ascorbate, oxygen and divalent-metal chelators/copper. [pam1983] Identification in pituitary tissue of a peptide alpha-amidation activity that acts on glycine-extended peptides and requires molecular oxygen, copper, and ascorbic acid. (1983). https://pubmed.ncbi.nlm.nih.gov/6576381/ DOI: 10.1073/pnas.80.16.5144
Complete structured claim and evidence
Ascorbate reduced enzyme-bound copper in purified bovine dopamine beta-hydroxylase from Cu(II) to Cu(I), as examined by X-ray absorption spectroscopy.
L-Ascorbate → Ascorbate-reduced bovine dopamine beta-hydroxylase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Bovine dopamine beta-hydroxylase X-ray absorption and EXAFS
exposure
Ascorbate reduction of purified Cu(II)-DBH to Cu(I)-DBH.
limitations
Purified bovine enzyme, not a dietary copper-status measurement. Scott 1988 and Blumberg 1989 disagree on the detailed coordination change and heavy-atom ligation; this record retains only the shared Cu(II)-to-Cu(I) redox conclusion.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Bos taurus
plain_language
Vitamin C supplies reducing power to copper held inside this neurotransmitter enzyme.
primary_references
[scott1988] The copper sites of dopamine beta-hydroxylase: an X-ray absorption spectroscopic study. (1988). https://pubmed.ncbi.nlm.nih.gov/3179263/ DOI: 10.1021/bi00415a005 [blumberg1989] X-ray absorption spectroscopic study of the active copper sites in dopamine beta-hydroxylase. (1989). https://pubmed.ncbi.nlm.nih.gov/2703478/ DOI: 10.1016/s0021-9258(18)83307-5
tissue_or_cell_type
Adrenal-medullary enzyme preparation
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 793–805
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine dopamine beta-hydroxylase X-ray absorption and EXAFS · source_derived_draft · unverified_draft
### vc-enzyme-dbh-copper-reduction Ascorbate reduced enzyme-bound copper in purified bovine dopamine beta-hydroxylase from Cu(II) to Cu(I), as examined by X-ray absorption spectroscopy. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C supplies reducing power to copper held inside this neurotransmitter enzyme. organism: Bos taurus tissue_or_cell_type: Adrenal-medullary enzyme preparation experimental_model: Bovine dopamine beta-hydroxylase X-ray absorption and EXAFS limitations: Purified bovine enzyme, not a dietary copper-status measurement. Scott 1988 and Blumberg 1989 disagree on the detailed coordination change and heavy-atom ligation; this record retains only the shared Cu(II)-to-Cu(I) redox conclusion. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Ascorbate reduction of purified Cu(II)-DBH to Cu(I)-DBH. [scott1988] The copper sites of dopamine beta-hydroxylase: an X-ray absorption spectroscopic study. (1988). https://pubmed.ncbi.nlm.nih.gov/3179263/ DOI: 10.1021/bi00415a005 [blumberg1989] X-ray absorption spectroscopic study of the active copper sites in dopamine beta-hydroxylase. (1989). https://pubmed.ncbi.nlm.nih.gov/2703478/ DOI: 10.1016/s0021-9258(18)83307-5
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
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
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
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
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
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
Lipoic acid did not prevent intracellular ascorbate loss caused by the extracellular copper/LDL challenge in the same study.
Lipoic acid → Human endothelial intracellular ascorbate pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"}
experimental_model
Human endothelial-cell and extracellular LDL oxidation experiments
exposure
40–80 micromolar lipoic acid; menadione or copper/LDL challenge
limitations
Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line and human LDL
plain_language
Protection of LDL did not guarantee protection of intracellular vitamin C.
primary_references
[ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
tissue_or_cell_type
EA.hy926 endothelial cells; extracellular LDL
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1027–1038
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human endothelial-cell and extracellular LDL oxidation experiments · source_derived_draft · unverified_draft
### ala-copper-challenge-ascorbate-null Lipoic acid did not prevent intracellular ascorbate loss caused by the extracellular copper/LDL challenge in the same study. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protection of LDL did not guarantee protection of intracellular vitamin C. organism: Human cell line and human LDL tissue_or_cell_type: EA.hy926 endothelial cells; extracellular LDL experimental_model: Human endothelial-cell and extracellular LDL oxidation experiments limitations: Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts. exposure: 40–80 micromolar lipoic acid; menadione or copper/LDL challenge evidence_span: {"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"} [ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
Complete structured claim and evidence
Oxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model.
Dihydrolipoic acid-copper complexes → Copper-driven LDL oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"}
experimental_model
Cell-free human LDL oxidation and electron-spin-resonance assays
exposure
Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied
limitations
Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human LDL; cell-free chemistry
plain_language
Metal binding was not a permanent guarantee against oxidation.
primary_references
[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
tissue_or_cell_type
LDL and copper/DHLA solutions
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1066–1077
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free human LDL oxidation and electron-spin-resonance assays · source_derived_draft · unverified_draft
### ala-dhla-copper-oxygen Oxidation destabilized DHLA-copper complexes near physiological pH, with renewed LDL oxidation and radical detection in the model. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Metal binding was not a permanent guarantee against oxidation. organism: Human LDL; cell-free chemistry tissue_or_cell_type: LDL and copper/DHLA solutions experimental_model: Cell-free human LDL oxidation and electron-spin-resonance assays limitations: Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy. exposure: Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied evidence_span: {"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"} [ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
Complete structured claim and evidence
DHLA favored copper reduction when copper was in excess and chelation when DHLA was in excess.
Free dihydrolipoic acid / DHLA → Copper(II) ion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"}
experimental_model
Cell-free human LDL oxidation and electron-spin-resonance assays
exposure
Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied
limitations
Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human LDL; cell-free chemistry
plain_language
Whether copper was bound or chemically reduced depended on the relative amounts.
primary_references
[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
tissue_or_cell_type
LDL and copper/DHLA solutions
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1053–1064
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free human LDL oxidation and electron-spin-resonance assays · source_derived_draft · unverified_draft
### ala-dhla-copper-ratio DHLA favored copper reduction when copper was in excess and chelation when DHLA was in excess. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Whether copper was bound or chemically reduced depended on the relative amounts. organism: Human LDL; cell-free chemistry tissue_or_cell_type: LDL and copper/DHLA solutions experimental_model: Cell-free human LDL oxidation and electron-spin-resonance assays limitations: Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy. exposure: Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied evidence_span: {"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"} [ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
Complete structured claim and evidence
DHLA delayed copper-driven LDL oxidation, whereas oxidized lipoic acid did not protect in this cell-free assay.
Free dihydrolipoic acid / DHLA → Copper-driven LDL oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"}
experimental_model
Cell-free human LDL oxidation and electron-spin-resonance assays
exposure
Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied
limitations
Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human LDL; cell-free chemistry
plain_language
Reduced and oxidized forms behaved differently in the same chemical test.
primary_references
[ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
tissue_or_cell_type
LDL and copper/DHLA solutions
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1040–1051
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free human LDL oxidation and electron-spin-resonance assays · source_derived_draft · unverified_draft
### ala-dhla-ldl-protection DHLA delayed copper-driven LDL oxidation, whereas oxidized lipoic acid did not protect in this cell-free assay. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced and oxidized forms behaved differently in the same chemical test. organism: Human LDL; cell-free chemistry tissue_or_cell_type: LDL and copper/DHLA solutions experimental_model: Cell-free human LDL oxidation and electron-spin-resonance assays limitations: Metal binding, reduction and radical production depend on ratio, oxygen and pH; not evidence for human metal-detoxification efficacy. exposure: Copper 5 micromolar; DHLA 0–20 micromolar; oxygen and pH varied evidence_span: {"source_cache": "artifacts/ala-research/9680174.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1", "start_char": 0, "end_char": 2034, "text_sha256": "ac15770e92102947345520296b7795e8ff2dca2c345ac76c14b929fbd19739f1"} [ala-p9680174] Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation. (1998). https://pubmed.ncbi.nlm.nih.gov/9680174/ DOI: 10.1016/s0891-5849(98)00048-3
Complete structured claim and evidence
Lipoic acid blunted copper-driven LDL oxidation and associated vitamin E consumption in the endothelial-cell experiment.
Lipoic acid → LDL vitamin E consumption during oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"}
experimental_model
Human endothelial-cell and extracellular LDL oxidation experiments
exposure
40–80 micromolar lipoic acid; menadione or copper/LDL challenge
limitations
Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human cell line and human LDL
plain_language
The extracellular lipoprotein compartment showed less oxidative damage.
primary_references
[ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
tissue_or_cell_type
EA.hy926 endothelial cells; extracellular LDL
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 1014–1025
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human endothelial-cell and extracellular LDL oxidation experiments · source_derived_draft · unverified_draft
### ala-ldl-vitamin-e-sparing Lipoic acid blunted copper-driven LDL oxidation and associated vitamin E consumption in the endothelial-cell experiment. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The extracellular lipoprotein compartment showed less oxidative damage. organism: Human cell line and human LDL tissue_or_cell_type: EA.hy926 endothelial cells; extracellular LDL experimental_model: Human endothelial-cell and extracellular LDL oxidation experiments limitations: Compartment and oxidant matter; intracellular vitamin C and LDL vitamin E are distinct readouts. exposure: 40–80 micromolar lipoic acid; menadione or copper/LDL challenge evidence_span: {"source_cache": "artifacts/ala-research/18026819.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a", "start_char": 0, "end_char": 1329, "text_sha256": "a4dff4887489013858d07ce07ba538c62702962afa1588ae7cc83e308648e53a"} [ala-p18026819] alpha-Lipoic acid and ascorbate prevent LDL oxidation and oxidant stress in endothelial cells. (2008). https://pubmed.ncbi.nlm.nih.gov/18026819/ DOI: 10.1007/s11010-007-9650-z
Complete structured claim and evidence
Tetrathiomolybdate formed a stable sulfur-bridged copper-molybdenum cluster with yeast Atx1.
Tetrathiomolybdate / MoS4(2-) → Saccharomyces cerevisiae copper chaperone / Atx1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/19965379.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57", "start_char": 0, "end_char": 950, "text_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57"}
experimental_model
Yeast Atx1 crystallography, spectroscopy and copper-transfer experiments
exposure
Tetrathiomolybdate exposure
limitations
Drug and yeast-protein chemistry; not evidence that normal human dietary molybdate strips copper from proteins.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Saccharomyces cerevisiae proteins; comparison with animal drug complexes
plain_language
A sulfur-rich molybdenum drug can trap copper in a protein complex.
primary_references
[mo-p19965379] Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation. (2010). https://pubmed.ncbi.nlm.nih.gov/19965379/ DOI: 10.1126/science.1179907
tissue_or_cell_type
Purified copper chaperones
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1600–1611
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast Atx1 crystallography, spectroscopy and copper-transfer experiments · source_derived_draft · unverified_draft
### mo-ttm-copper-cluster Tetrathiomolybdate formed a stable sulfur-bridged copper-molybdenum cluster with yeast Atx1. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sulfur-rich molybdenum drug can trap copper in a protein complex. organism: Saccharomyces cerevisiae proteins; comparison with animal drug complexes tissue_or_cell_type: Purified copper chaperones experimental_model: Yeast Atx1 crystallography, spectroscopy and copper-transfer experiments limitations: Drug and yeast-protein chemistry; not evidence that normal human dietary molybdate strips copper from proteins. exposure: Tetrathiomolybdate exposure evidence_span: {"source_cache": "artifacts/molybdenum-research/19965379.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57", "start_char": 0, "end_char": 950, "text_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57"} [mo-p19965379] Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation. (2010). https://pubmed.ncbi.nlm.nih.gov/19965379/ DOI: 10.1126/science.1179907
Complete structured claim and evidence
The drug-Atx1 complex inhibited copper transfer between copper-trafficking proteins in the experimental system.
Tetrathiomolybdate-copper-yeast Atx1 cluster → Saccharomyces cerevisiae copper-transporting ATPase / Ccc2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/19965379.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57", "start_char": 0, "end_char": 950, "text_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57"}
experimental_model
Yeast Atx1 crystallography, spectroscopy and copper-transfer experiments
exposure
Tetrathiomolybdate exposure
limitations
Drug and yeast-protein chemistry; not evidence that normal human dietary molybdate strips copper from proteins.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Saccharomyces cerevisiae proteins; comparison with animal drug complexes
plain_language
Trapping the copper interrupted its handoff to another protein.
primary_references
[mo-p19965379] Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation. (2010). https://pubmed.ncbi.nlm.nih.gov/19965379/ DOI: 10.1126/science.1179907
tissue_or_cell_type
Purified copper chaperones
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1613–1624
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Yeast Atx1 crystallography, spectroscopy and copper-transfer experiments · source_derived_draft · unverified_draft
### mo-ttm-copper-transfer The drug-Atx1 complex inhibited copper transfer between copper-trafficking proteins in the experimental system. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Trapping the copper interrupted its handoff to another protein. organism: Saccharomyces cerevisiae proteins; comparison with animal drug complexes tissue_or_cell_type: Purified copper chaperones experimental_model: Yeast Atx1 crystallography, spectroscopy and copper-transfer experiments limitations: Drug and yeast-protein chemistry; not evidence that normal human dietary molybdate strips copper from proteins. exposure: Tetrathiomolybdate exposure evidence_span: {"source_cache": "artifacts/molybdenum-research/19965379.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57", "start_char": 0, "end_char": 950, "text_sha256": "166eb55335870bc9843fdb0c61becaa318603b25c601bbfa8f69a469dab89e57"} [mo-p19965379] Tetrathiomolybdate inhibits copper trafficking proteins through metal cluster formation. (2010). https://pubmed.ncbi.nlm.nih.gov/19965379/ DOI: 10.1126/science.1179907
Complete structured claim and evidence
Twenty of 28 participants met the copper endpoint; mean corrected non-ceruloplasmin copper fell 72% at 24 weeks.
Bis-choline tetrathiomolybdate → Corrected non-ceruloplasmin-bound plasma copper source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/28988934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ca2c31c7a405be35fb18be79af77bbac1efc1dceb26a625f5a5cd35121cba7c", "start_char": 0, "end_char": 3591, "text_sha256": "6ca2c31c7a405be35fb18be79af77bbac1efc1dceb26a625f5a5cd35121cba7c"}
experimental_model
Open-label phase 2 trial in 28 adults with Wilson disease
exposure
24 weeks of response-adjusted bis-choline tetrathiomolybdate
limitations
No blinded comparator. Pharmacological copper-binding drug, not nutritional molybdenum; endpoint corrects for drug-bound copper.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Homo sapiens
plain_language
The drug changed a copper measure in patients with a copper-accumulation disorder.
primary_references
[mo-p28988934] Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study. (2017). https://pubmed.ncbi.nlm.nih.gov/28988934/ DOI: 10.1016/s2468-1253(17)30293-5
tissue_or_cell_type
Plasma copper and clinical safety
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1639–1650
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Open-label phase 2 trial in 28 adults with Wilson disease · source_derived_draft · unverified_draft
### mo-ttm-human-copper Twenty of 28 participants met the copper endpoint; mean corrected non-ceruloplasmin copper fell 72% at 24 weeks. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The drug changed a copper measure in patients with a copper-accumulation disorder. organism: Homo sapiens tissue_or_cell_type: Plasma copper and clinical safety experimental_model: Open-label phase 2 trial in 28 adults with Wilson disease limitations: No blinded comparator. Pharmacological copper-binding drug, not nutritional molybdenum; endpoint corrects for drug-bound copper. exposure: 24 weeks of response-adjusted bis-choline tetrathiomolybdate evidence_span: {"source_cache": "artifacts/molybdenum-research/28988934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ca2c31c7a405be35fb18be79af77bbac1efc1dceb26a625f5a5cd35121cba7c", "start_char": 0, "end_char": 3591, "text_sha256": "6ca2c31c7a405be35fb18be79af77bbac1efc1dceb26a625f5a5cd35121cba7c"} [mo-p28988934] Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study. (2017). https://pubmed.ncbi.nlm.nih.gov/28988934/ DOI: 10.1016/s2468-1253(17)30293-5
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.

Copper cannot reach the body when intestinal transport fails

Condition: machinery_impairment · Intestinal epithelial Slc31a1 deletion

Normal role: Intestinal Ctr1 makes dietary copper available to peripheral tissues.

Recorded consequence: Systemic copper shortage, hepatic iron accumulation and impaired growth or survival.

Scope: Genetic mouse intestinal Ctr1 knockout; not an intake threshold

A copper courier can fail even when cellular copper rises

Condition: machinery_impairment · Atox1 loss

Normal role: Atox1 supports delivery toward copper-export machinery.

Recorded consequence: Reduced efflux and impaired copper-responsive ATP7A traffic despite cellular copper accumulation.

Scope: Mouse embryonic fibroblasts

Copper can reach mitochondria but fail to reach its respiratory enzyme

Condition: machinery_impairment · Loss of a mitochondrial copper carrier or assembly factor

Normal role: Copper delivery and assembly steps supply cytochrome c oxidase.

Recorded consequence: Respiratory-enzyme deficiency may coexist with misplaced copper; bypass outcomes depend on the broken step.

Scope: Cell and biochemical mitochondrial transport studies; not ordinary dietary deficiency

An assembly defect can make cells lose copper

Condition: machinery_impairment · Specific SCO1 or SCO2 variants

Normal role: SCO proteins participate in COX assembly and copper homeostasis.

Recorded consequence: Cellular copper deficiency associated with increased efflux.

Scope: Human patient cells; tissue- and allele-dependent

SOD1 can be present but missing its copper

Condition: machinery_impairment · Ccs deletion

Normal role: CCS assists SOD1 copper incorporation.

Recorded consequence: Reduced SOD1 copper loading and activity despite normal protein abundance.

Scope: Mouse Ccs knockout

Marginal copper restriction worsens the liver response to high fructose

Condition: nutrient_deficiency · Copper restricted to 1.6 versus 6 mg/kg diet with 30% fructose water

Normal role: Adequate dietary copper supports copper-dependent physiology.

Recorded consequence: Copper status and liver injury worsen, with loss of the usual duodenal Ctr1 induction.

Scope: Four-week rat dietary experiment

Iron can be abundant in tissues yet poorly available in blood

Condition: machinery_impairment · Ceruloplasmin and/or hephaestin loss

Normal role: Copper-dependent ferroxidases assist systemic iron distribution.

Recorded consequence: Iron retention and, depending on the model, low circulating iron and anemia.

Scope: Mouse Cp/Heph knockout studies; not all human anemia

When copper cannot be handed to its enzyme

Condition: machinery_impairment · Deletion of the chaperone gene, or strictly limited free copper.

Normal role: The copper chaperone inserts copper directly into superoxide dismutase.

Recorded consequence: The dismutase stays in its inactive copper-free form unless copper is raised or the cell’s copper scavengers are removed.

Scope: Yeast genetics with purified proteins

Too little copper can impair iron use

Condition: nutrient_deficiency · Experimental dietary copper depletion

Normal role: Copper availability supports intestinal hephaestin and iron handling.

Recorded consequence: Lower enterocyte hephaestin and reduced iron absorption.

Scope: Controlled rat feeding experiment

Vascular specimens from patients with type 2 diabetes showed lower ATP7A protein.

Condition: biomarker_context · Type 2 diabetes vascular specimens

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

Recorded consequence: Vascular specimens from patients with type 2 diabetes showed lower ATP7A protein.

Scope: Human vascular specimens; primary abstract reviewed

An antioxidant enzyme can lose activity when its copper delivery falls

Condition: machinery_impairment · Reduced vascular ATP7A in mouse type 1 diabetes models

Normal role: ATP7A supplies copper to extracellular SOD3.

Recorded consequence: Lower SOD3 specific activity and impaired endothelial relaxation.

Scope: Mouse vessels and ex-vivo intervention

When dopamine beta-hydroxylase is short of copper

Condition: nutrient_deficiency · Copper occupancy below that stoichiometry in the purified enzyme.

Normal role: Eight copper atoms per tetramer are required for maximal conversion of dopamine to noradrenaline.

Recorded consequence: Catalytic rate falls in proportion to the copper present.

Scope: Purified bovine adrenal enzyme

Akt2-null vessels or vascular smooth-muscle cells had lower SOD3 activity, rescued by ATP7A overexpression.

Condition: machinery_impairment · Akt2 loss

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

Recorded consequence: Akt2-null vessels or vascular smooth-muscle cells had lower SOD3 activity, rescued by ATP7A overexpression.

Scope: Mouse Akt2-null vascular experiments; primary abstract reviewed

Copper-related blood measurements can disagree

Condition: biomarker_context · A dietary intervention or illness changes one measured endpoint

Normal role: Copper concentration, enzyme amount and enzyme activity measure different properties.

Recorded consequence: A lower enzyme activity alone may not establish lower copper absorption or depleted body stores.

Scope: Human vitamin C intervention and other separately scoped studies

What falls when dietary copper is experimentally depleted?

Condition: nutrient_deficiency · Controlled low-copper diet

Normal role: Dietary copper supports circulating copper and copper-dependent enzymes.

Recorded consequence: Lower plasma copper, ceruloplasmin activity and protein, and urinary copper.

Scope: Eleven young men in a metabolic-ward study

Gastric bypass can be followed by copper shortage

Condition: nutrient_deficiency · Roux-en-Y gastric bypass in the observed cohorts

Normal role: Intestinal delivery sustains copper-dependent blood and nervous-system function.

Recorded consequence: Low copper status with hematologic or neuromuscular abnormalities in some patients.

Scope: Human postoperative observational cohorts

Very high iron can create a shortage of another mineral

Condition: nutrient_deficiency · Very-high-iron feeding

Normal role: Copper supports ferroxidase function and iron distribution.

Recorded consequence: Systemic copper deficiency with anemia in the rat model.

Scope: Five-week weanling-rat feeding experiment

Copper deficiency can impair balance and nerve function

Condition: nutrient_deficiency · Clinically documented copper deficiency

Normal role: Adequate copper supports nervous-system function through multiple molecular routes.

Recorded consequence: Sensory ataxia with peripheral and central pathway abnormalities.

Scope: Six-patient neurophysiology series; causal enzyme unresolved

Early copper delivery in Menkes disease depends partly on remaining machinery

Condition: machinery_impairment · Inherited ATP7A dysfunction

Normal role: ATP7A supports systemic copper routing.

Recorded consequence: Severe copper-distribution failure; early treatment results vary with residual function.

Scope: Human neonatal treatment cohort with historical controls

A copper-export defect can cause toxic accumulation

Condition: machinery_impairment · Inherited ATP7B dysfunction in Wilson disease

Normal role: ATP7B participates in biliary copper disposal.

Recorded consequence: Abnormal copper accumulation requiring disease-specific control.

Scope: CHELATE studied maintenance treatment in stable adults

Prolonged zinc therapy can produce copper shortage

Condition: nutrient_deficiency · Prolonged zinc treatment in the reported sickle cell population

Normal role: Copper availability supports copper-dependent proteins and hematological function.

Recorded consequence: Low circulating copper with microcytosis and relative neutropenia; response to copper administration.

Scope: Adult clinical case evidence, not a universal dietary dose response.

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.

Alpha-lipoic acid: cofactor assembly, redox signaling 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
Copper: transport, cuproenzymes, deficiency, excess 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
Diabetes cascade: targeted primary-source supplementSee claim-local references; curated paraphrases reviewed 2026-09-20. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (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
Manganese: enzyme cofactors, glycosylation, transport 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
Molybdenum: cofactor assembly, sulfur metabolism 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
Vitamin C: 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
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 combination of biomarkers best identifies early, tissue-specific copper deficiency?Circulating copper, ceruloplasmin concentration, oxidase activity and erythrocyte SOD respond differently; no universal diagnostic algorithm is established by this collection.
Which neurologic changes are reversible, and over what time window, in each cause of acquired copper deficiency?The included clinical series and biochemical pathways do not supply a universal recovery prediction.
Which copper-dependent step explains an individual case of neurologic injury or neutropenia?Patient syndromes establish a copper connection but usually do not isolate one causal cuproenzyme; multiple routes may contribute.
Does increasing copper improve histamine-related symptoms when systemic copper status is adequate?AOC1 structure and substrate specificity do not establish a supplementation benefit or a clinical diagnosis.
Which nutrient combinations have clinically meaningful copper interactions at ordinary human intakes?Cell chemistry, high-dose interventions, rat diets and human clinical deficiency reports have different exposure ranges and cannot be merged into one synergy score.
What explains the human homocysteine and folate shifts after high copper intake?The small human study did not demonstrate copper-dependent human methionine synthase; the causal pathway remains unresolved.
Which physiological ligands carry copper through each intestinal and mitochondrial transport step in humans?Transport activity and compartment models do not identify every in-vivo copper complex or flux.
How broadly does the 2026 SLC25A3 export model apply across human tissues and variants?The key knockout experiments used rat cardiomyoblasts with supporting bacterial assays; compartment-specific flux needs further validation.

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

Copper

The mechanisms

Human hephaestin catalyzed diferric transferrin formation from Fe(II) and apotransferrin in vitro.

Whole-body Heph/Cp double-knockout mice developed severe anemia and low serum iron despite iron-loaded tissues.

Copper-deficient rats had enterocyte hephaestin protein at about 35% of copper-adequate controls.

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.

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

Human CTR1 supported high-affinity, saturable, metal-selective copper uptake at the plasma membrane.

Copper-loaded ATOX1 activated ATP7B ATP hydrolysis while changing interactions among its first three metal-binding domains.

Elesclomol-copper increased mitochondrial copper but failed to restore COX1 abundance in rat Slc25a3-null cells.

Glutathione reduced fully oxidized apo-COX17 back to the two-disulfide state in the protein-transfer system.

Ccs-null mice retained normal SOD1 protein abundance but had markedly reduced SOD1 copper incorporation and activity.

Human DBH is the copper-enzyme step converting dopamine to norepinephrine; the study resolved its catalytic-core architecture.

Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites.

CTR1-mediated radiocopper transport was energy independent and increased at acidic extracellular pH and high extracellular potassium in the assay.

Expressed mouse Steap2 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system.

Expressed mouse Steap3 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system.

Expressed mouse Steap4 reduced Cu(II) to Cu(I) and increased cellular copper uptake in the tested human cell system.

Intestinal Ctr1 deletion reduced peripheral copper availability and caused neonatal growth failure and cardiac hypertrophy in mice.

Mice lacking intestinal Ctr1 developed hepatic iron overload alongside systemic copper deficiency.

A single postnatal copper administration partially rescued growth and viability in intestinal Ctr1 knockout mice.

Dietary copper limitation increased total and apically localized Ctr1 protein in mouse intestine.

Atox1-deficient fibroblasts accumulated copper because cellular copper efflux was reduced.

Atox1 loss impaired copper-responsive ATP7A movement from the Golgi even when intracellular copper concentrations were matched.

Copper transfer from ATOX1 reduced interactions within ATP7B MBD1-3 and increased domain mobility.

Elevated copper redirected ATP7B from the trans-Golgi network to a subset of lysosomes.

Lysosomal ATP7B transported copper into the lysosomal lumen.

ATP7B interaction with dynactin p62 supported movement of copper-containing lysosomes toward the hepatocyte canalicular pole.

Stimulating lysosomal exocytosis increased ATP7B delivery toward the canalicular membrane and copper release into the biliary space.

Ctr2 was required for normal formation of the ectodomain-cleaved form of Ctr1 in mice.

The truncated Ctr1 form mobilized endosomal copper stores, whereas full-length Ctr1 efficiently supported plasma-membrane uptake.

Copper deficiency lowered ATP7A abundance in mouse peripheral tissues; subcutaneous copper restored it.

Low systemic copper increased intestinal ATP7A, while subcutaneous copper lowered it in the same mouse study.

SLC25A3 supported copper transport in heterologous assays and reconstituted liposomes.

SLC25A3 knockdown or deletion caused COX deficiency in human and mouse cell models; copper addition suppressed the defects in that study.

Human SLC25A3 expression increased copper export from copper-loaded Lactococcus lactis, supporting an export function.

Slc25a3-null rat cells exposed to elesclomol-copper showed increased DLAT oligomerization and loss of lipoylated DLAT and DLST.

Elesclomol-copper reduced the iron-sulfur proteins SDHB and ACO2 in Slc25a3-null rat cells.

Oral elesclomol without extra copper supplementation rescued neonatal mortality in intestine-specific Ctr1 knockout mice.

Cu(I)-COX17 with two disulfides transferred copper and two electrons to oxidized SCO1, producing copper-loaded SCO1 and apo-COX17 with three disulfides.

The copper-and-electron-coupled transfer observed with SCO1 did not occur with SCO2 under the same biochemical conditions.

COA6 acted as a thiol reductase for critical cysteine disulfides in SCO1.

COA6 reduced critical SCO2 disulfides; SCO2 cysteines in its CX3CXnH domain mediated COA6 interaction.

COA6 loss caused combined respiratory complex I and IV deficiency in human cells.

COA6 loss reduced membrane potential and impaired potential-dependent protein import across the inner mitochondrial membrane.

SCO1-associated cellular copper deficiency reflected increased copper efflux rather than reduced high-affinity uptake in the studied patient-cell models.

SCO2 variants also produced tissue- and allele-specific cellular copper deficiency through increased efflux.

SCO2 overexpression suppressed the cellular copper-deficiency phenotype; SCO1 overexpression did not provide the same rescue.

Ccs deletion did not measurably disrupt overall copper uptake, distribution or incorporation into the other cuproenzymes examined.

Recombinant copper-containing human hephaestin oxidized Fe(II), with an apparent substrate Km of 2.1 micromolar.

Cp-null mice had impaired iron release from hepatocytes and reticuloendothelial cells, while measured iron absorption and plasma turnover were comparable to controls.

By one year, Cp-null mice had three- to sixfold higher liver and spleen iron with increased serum ferritin.

Whole-body double deletion loaded iron into duodenum, liver, heart and pancreas; intestine-specific Heph deletion with global Cp loss produced a more restricted distribution.

Both Heph/Cp double-knockout models still absorbed oral iron tracer, but retained an abnormally high fraction in the liver.

Copper-deficient male and female rats absorbed about 60% and 70%, respectively, of the iron absorbed by copper-adequate controls.

Dietary copper deficiency caused little ferroportin mRNA change; protein responses varied and did not account for the anemia across the rodent models.

ATP7A silencing impaired iron uptake and efflux in differentiated human Caco-2 cells.

Rat Atp7a knockdown increased hephaestin expression more than tenfold and increased ferroxidase activity, even though net iron uptake and efflux fell.

Atp7a silencing reduced LOX/LOXL activity in mouse mammary and lung carcinoma models.

Atp7a silencing reduced LOX-associated metastatic behavior, including focal-adhesion signaling and lung myeloid recruitment in the tested mammary tumor model.

Atp7a overexpression restored reduced SOD3 specific activity in diabetic mouse vessels.

SOD3 gene transfer rescued impaired endothelium-dependent relaxation in the tested diabetic mouse arteries.

Insulin treatment increased ATP7A expression in vascular smooth muscle cells and restored SOD3 activity in diabetic mouse vessel culture.

Tyrosinase copper loading was transient and inefficient in the Golgi; ATP7A supplied copper for reloading in melanosomes.

ATP7A localization to melanosomes depended on BLOC-1 in mouse melanocytes.

Human diamine oxidase has a substrate pocket adapted to diamines including histamine, distinct from that of AOC3.

The human AOC3 structure contained an active-site copper ion and TPQ in its active off-copper conformation.

Ceruloplasmin copper incorporation was cooperative, and its final conformational state required occupation of all six copper-binding sites in the tested system.

The aceruloplasminemia-associated G631R variant was synthesized and secreted as apoceruloplasmin in the cell-expression study.

Human DBH displayed open and closed active-site conformations; the closed structure placed its two copper-binding sites about 4–5 angstroms apart.

The 605 mg/day vitamin C period reduced ceruloplasmin oxidase activity by about 21% in the controlled feeding study.

The study found no significant vitamin-C-period effect on copper absorption, retention, serum copper or ceruloplasmin protein despite the oxidase-activity change.

Ceruloplasmin oxidase activity decreased during 1500 mg/day vitamin C supplementation; the serum copper decline was not statistically significant.

High dietary iron reduced copper absorption in copper-deficient rats but not in copper-adequate rats in the factorial study.

High iron together with dietary ascorbate aggravated anemia in copper-deficient rats.

Adding iron to the zinc intervention prevented adverse iron-status changes but did not prevent the fall in erythrocyte Cu/Zn-SOD activity.

High copper intake in nine men produced small decreases in plasma homocysteine and folate, without changes in B12 or PLP measures.

Copper inhibited mouse PDE3B activity in the biochemical and adipocyte study.

Copper-dependent PDE3B inhibition increased cAMP signaling and promoted lipolysis in 3T3-L1 adipocytes.

MEK1 mutations disrupting copper binding reduced BRAF V600E-driven signaling in the tested human and mouse systems.