Nutrient chapter

Manganese

Dietary manganese; distinct from its divalent ion and transporter-dependent cellular uptake.

100 recorded mechanisms · 22 availability situations · 5 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Mouse ZIP14 directly mediated 54Mn(II) uptake in RNA-injected Xenopus oocytes.
Mouse ZIP14 (Slc39a14) → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
RNA-injected Xenopus oocytes with radiolabeled metal uptake
exposure
54Mn transport compared with uninjected controls.
limitations
Transport capacity is not proof that manganese supplements improve zinc transport or vice versa.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mouse protein in Xenopus laevis oocytes
plain_language
ZIP14 could carry manganese as well as zinc in this experiment.
primary_references
[zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 492–503
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RNA-injected Xenopus oocytes with radiolabeled metal uptake · source_derived_draft · unverified_draft
### zinc-trans-zip14-manganese-influx Mouse ZIP14 directly mediated 54Mn(II) uptake in RNA-injected Xenopus oocytes. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: ZIP14 could carry manganese as well as zinc in this experiment. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: RNA-injected Xenopus oocytes with radiolabeled metal uptake limitations: Transport capacity is not proof that manganese supplements improve zinc transport or vice versa. exposure: 54Mn transport compared with uninjected controls. cross_nutrient: true [zinc-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
ZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells.
Mouse ZIP8 (Slc39a8) → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
experimental_model
Polarized proximal-tubule culture with separately accessible apical and basolateral compartments
exposure
ZIP8 siRNA versus controls during apical manganese exposure.
limitations
This is manganese uptake, not direct proof of zinc reabsorption by ZIP8; ZIP14 and DMT1 knockdowns also affected uptake in the paper.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Mus musculus
plain_language
A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side.
primary_references
[zinc-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
tissue_or_cell_type
Mouse proximal-tubule epithelial cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 531–542
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized proximal-tubule culture with separately accessible apical and basolateral compartments · source_derived_draft · unverified_draft
### zinc-trans-renal-zip8-manganese ZIP8-specific siRNA reduced manganese uptake from the apical side of polarized mouse proximal-tubule cells. Condition category: machinery_impairment nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter known to handle zinc also helped kidney-derived cells take up manganese from their lumen-facing side. organism: Mus musculus tissue_or_cell_type: Mouse proximal-tubule epithelial cells experimental_model: Polarized proximal-tubule culture with separately accessible apical and basolateral compartments limitations: This is manganese uptake, not direct proof of zinc reabsorption by ZIP8; ZIP14 and DMT1 knockdowns also affected uptake in the paper. exposure: ZIP8 siRNA versus controls during apical manganese exposure. cross_nutrient: true [zinc-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
Complete structured claim and evidence
Manganese acts as a cofactor in this reaction.
Mn2+ supports the reported SELENOO NAD-hydrolysis activity.
Mn2+ → SELENOO source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
experimental cells
experimental_model
Metal-dependent enzyme assays
limitations
Cofactor dependence does not establish nutritional limitation.
organism
mammalian
Selenium: literature corrections and mechanism additions · lines 450–460
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Metal-dependent enzyme assays · secondary_verified · secondary_verified
## manganese-supports-selenoo-nadase Manganese acts as a cofactor in this reaction. Mn2+ supports the reported SELENOO NAD-hydrolysis activity. Organism: mammalian Cell type: experimental cells Experimental model: Metal-dependent enzyme assays Limitations: Cofactor dependence does not establish nutritional limitation. Primary reference: [NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis](https://pubmed.ncbi.nlm.nih.gov/41806834/)
Complete structured claim and evidence
Reconstituted erythrocyte transketolase activity ranked Co2+ < Mn2+ < Ca2+ < Mg2+ in the tested assay.
Calcium ion → Human transketolase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution.
limitations
Replacement in vitro does not establish physiological substitution during Mg deficiency.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Several divalent metals supported this B1-dependent enzyme; magnesium worked best here.
primary_references
[jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5
tissue_or_cell_type
Erythrocyte enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 565–575
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. · source_derived_draft · unverified_draft
### mg-tkt-other-divalent-cations Reconstituted erythrocyte transketolase activity ranked Co2+ < Mn2+ < Ca2+ < Mg2+ in the tested assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several divalent metals supported this B1-dependent enzyme; magnesium worked best here. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. limitations: Replacement in vitro does not establish physiological substitution during Mg deficiency. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5
Complete structured claim and evidence
COLGALT1 transfers galactose from UDP-galactose to collagen hydroxylysine.
COLGALT1 → Collagen-bound 5-hydroxylysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human COLGALT1 with collagen peptides.
limitations
This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.
organism
Human
plain_language
A sugar is attached to a lysine residue that has already been hydroxylated.
primary_references
[colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 437–445
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human COLGALT1 with collagen peptides. · source_derived_draft · unverified_draft
### colgalt1-galactosylation COLGALT1 transfers galactose from UDP-galactose to collagen hydroxylysine. Plain language: A sugar is attached to a lysine residue that has already been hydroxylated. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Recombinant human COLGALT1 with collagen peptides. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
Complete structured claim and evidence
Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay.
Mn2+ → COLGALT1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human COLGALT1 metal-substitution assays.
limitations
Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive.
organism
Human
plain_language
Manganese is a catalytic partner for this collagen-sugar enzyme.
primary_references
[colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 447–455
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human COLGALT1 metal-substitution assays. · source_derived_draft · unverified_draft
### manganese-colgalt1 Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay. Plain language: Manganese is a catalytic partner for this collagen-sugar enzyme. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified human COLGALT1 metal-substitution assays. limitations: Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive. [colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
Complete structured claim and evidence
PLOD3 transfers glucose from UDP-glucose onto galactosyl-hydroxylysine in collagen.
PLOD3 → Collagen galactosyl-hydroxylysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human PLOD3-COLGALT1 complex structure and biochemical assays.
limitations
This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.
organism
Human
plain_language
A second sugar can be added after galactose.
primary_references
[kog-glycosylation-2025] The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation (2025). https://www.nature.com/articles/s41467-025-57768-9 DOI: 10.1038/s41467-025-57768-9
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 457–465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PLOD3-COLGALT1 complex structure and biochemical assays. · source_derived_draft · unverified_draft
### plod3-glucosylation PLOD3 transfers glucose from UDP-glucose onto galactosyl-hydroxylysine in collagen. Plain language: A second sugar can be added after galactose. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human PLOD3-COLGALT1 complex structure and biochemical assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [kog-glycosylation-2025] The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation (2025). https://www.nature.com/articles/s41467-025-57768-9 DOI: 10.1038/s41467-025-57768-9
Complete structured claim and evidence
PLOD3 hydroxylates peptidyl lysine using Fe(II), 2-oxoglutarate and oxygen.
PLOD3 → Collagen-bound lysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human PLOD3 structural and biochemical assays.
limitations
This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.
organism
Human
plain_language
The collagen enzyme needs an iron-containing catalytic site and reaction partners.
primary_references
[plod3-2018] Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3 (2018). https://www.nature.com/articles/s41467-018-05631-5 DOI: 10.1038/s41467-018-05631-5
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 417–425
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PLOD3 structural and biochemical assays. · source_derived_draft · unverified_draft
### plod3-collagen-hydroxylation PLOD3 hydroxylates peptidyl lysine using Fe(II), 2-oxoglutarate and oxygen. Plain language: The collagen enzyme needs an iron-containing catalytic site and reaction partners. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Recombinant human PLOD3 structural and biochemical assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [plod3-2018] Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3 (2018). https://www.nature.com/articles/s41467-018-05631-5 DOI: 10.1038/s41467-018-05631-5
Complete structured claim and evidence
Ascorbate supports sustained lysyl-hydroxylase activity; the enzyme can initially turn over without ascorbate.
L-Ascorbate → Collagen lysyl hydroxylase family source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified chick-embryo enzyme kinetics.
limitations
Family-level enzyme preparation, not a human PLOD isoform comparison or lysine-supplement trial.
organism
Chicken
plain_language
Vitamin C supports the reaction, but is not consumed in every coupled turnover.
primary_references
[plod-cofactor-1980] Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. (1980). https://pubmed.ncbi.nlm.nih.gov/6766066/ DOI: 10.1016/0005-2744(80)90040-6
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 427–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick-embryo enzyme kinetics. · source_derived_draft · unverified_draft
### ascorbate-lysyl-hydroxylase Ascorbate supports sustained lysyl-hydroxylase activity; the enzyme can initially turn over without ascorbate. Plain language: Vitamin C supports the reaction, but is not consumed in every coupled turnover. Condition category: normal organism: Chicken tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified chick-embryo enzyme kinetics. limitations: Family-level enzyme preparation, not a human PLOD isoform comparison or lysine-supplement trial. [plod-cofactor-1980] Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. (1980). https://pubmed.ncbi.nlm.nih.gov/6766066/ DOI: 10.1016/0005-2744(80)90040-6
Complete structured claim and evidence
Liver-specific Slc39a8 knockout lowered manganese in multiple organs and whole blood in mice.
Mouse liver-specific Slc39a8 knockout genotype → Systemic manganese content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression
exposure
Liver-specific Slc39a8 knockout versus controls.
limitations
This is a genetic conservation defect; the abstract does not supply dietary depletion thresholds.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Loss of liver ZIP8 depleted manganese beyond the liver.
primary_references
[mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
tissue_or_cell_type
Liver, bile and measured extrahepatic tissues
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 136–147
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression · source_derived_draft · unverified_draft
### mn-trans-hepatic-zip8-loss-tissue-mn Liver-specific Slc39a8 knockout lowered manganese in multiple organs and whole blood in mice. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of liver ZIP8 depleted manganese beyond the liver. organism: Mus musculus tissue_or_cell_type: Liver, bile and measured extrahepatic tissues experimental_model: Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression limitations: This is a genetic conservation defect; the abstract does not supply dietary depletion thresholds. exposure: Liver-specific Slc39a8 knockout versus controls. cross_nutrient: false [mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
Complete structured claim and evidence
Liver-directed AAV expression of human ZIP8 increased tissue and whole-blood manganese in mice.
Mouse liver human ZIP8 overexpression state → Systemic manganese content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression
exposure
Liver-specific AAV-human-ZIP8 versus study controls.
limitations
Overexpression in mice does not establish a nutritional intervention or human dosing.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus with human ZIP8 transgene
plain_language
Increasing liver ZIP8 increased manganese retained in the body.
primary_references
[mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
tissue_or_cell_type
Liver, bile and measured extrahepatic tissues
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 149–160
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression · source_derived_draft · unverified_draft
### mn-trans-hepatic-zip8-overexpression-tissue-mn Liver-directed AAV expression of human ZIP8 increased tissue and whole-blood manganese in mice. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing liver ZIP8 increased manganese retained in the body. organism: Mus musculus with human ZIP8 transgene tissue_or_cell_type: Liver, bile and measured extrahepatic tissues experimental_model: Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression limitations: Overexpression in mice does not establish a nutritional intervention or human dosing. exposure: Liver-specific AAV-human-ZIP8 versus study controls. cross_nutrient: false [mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
Complete structured claim and evidence
ZIP8-LSKO mice had increased bile manganese; ZIP8 localized to hepatocyte canalicular membranes, supporting biliary manganese reclamation.
Mouse liver-specific Slc39a8 knockout genotype → Biliary manganese concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression
exposure
Liver-specific Slc39a8 knockout versus controls.
limitations
Bile concentration and anatomical localization support reclamation; concentration is not itself a secretion-rate measurement.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Liver ZIP8 helps recover manganese from bile.
primary_references
[mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
tissue_or_cell_type
Liver, bile and measured extrahepatic tissues
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 162–173
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression · source_derived_draft · unverified_draft
### mn-trans-hepatic-zip8-loss-bile-mn ZIP8-LSKO mice had increased bile manganese; ZIP8 localized to hepatocyte canalicular membranes, supporting biliary manganese reclamation. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Liver ZIP8 helps recover manganese from bile. organism: Mus musculus tissue_or_cell_type: Liver, bile and measured extrahepatic tissues experimental_model: Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression limitations: Bile concentration and anatomical localization support reclamation; concentration is not itself a secretion-rate measurement. exposure: Liver-specific Slc39a8 knockout versus controls. cross_nutrient: false [mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
Complete structured claim and evidence
Liver-directed human ZIP8 overexpression decreased bile manganese in mice.
Mouse liver human ZIP8 overexpression state → Biliary manganese concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression
exposure
Liver-specific AAV-human-ZIP8 versus study controls.
limitations
Bile concentration is distinct from measured excretion flux.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus with human ZIP8 transgene
plain_language
More liver ZIP8 left less manganese in bile.
primary_references
[mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
tissue_or_cell_type
Liver, bile and measured extrahepatic tissues
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 175–186
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression · source_derived_draft · unverified_draft
### mn-trans-hepatic-zip8-overexpression-bile-mn Liver-directed human ZIP8 overexpression decreased bile manganese in mice. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: More liver ZIP8 left less manganese in bile. organism: Mus musculus with human ZIP8 transgene tissue_or_cell_type: Liver, bile and measured extrahepatic tissues experimental_model: Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression limitations: Bile concentration is distinct from measured excretion flux. exposure: Liver-specific AAV-human-ZIP8 versus study controls. cross_nutrient: false [mn-trans-28481222] Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity. (2017). https://pubmed.ncbi.nlm.nih.gov/28481222/ DOI: 10.1172/jci90896
Complete structured claim and evidence
ZIP14 deletion in human Caco-2 Transwell cultures impaired basolateral-to-apical manganese transport.
Caco-2 SLC39A14 knockout genotype → Intestinal basolateral-to-apical manganese flux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
ZIP14-deficient human Caco-2 Transwell monolayers
exposure
ZIP14-deficient versus control Caco-2 Transwell monolayers.
limitations
Directional flux in a transformed cell-line model is not a human fractional-absorption estimate.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Intestinal ZIP14 supported movement of manganese toward the gut lumen.
primary_references
[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
tissue_or_cell_type
Caco-2 intestinal epithelial model
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 188–199
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ZIP14-deficient human Caco-2 Transwell monolayers · source_derived_draft · unverified_draft
### mn-trans-intestinal-zip14-secretory ZIP14 deletion in human Caco-2 Transwell cultures impaired basolateral-to-apical manganese transport. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intestinal ZIP14 supported movement of manganese toward the gut lumen. organism: Homo sapiens tissue_or_cell_type: Caco-2 intestinal epithelial model experimental_model: ZIP14-deficient human Caco-2 Transwell monolayers limitations: Directional flux in a transformed cell-line model is not a human fractional-absorption estimate. exposure: ZIP14-deficient versus control Caco-2 Transwell monolayers. cross_nutrient: false [mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
Complete structured claim and evidence
ZIP14 deletion in human Caco-2 Transwell cultures increased apical-to-basolateral manganese transport.
Caco-2 SLC39A14 knockout genotype → Intestinal apical-to-basolateral manganese flux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
ZIP14-deficient human Caco-2 Transwell monolayers
exposure
ZIP14-deficient versus control Caco-2 Transwell monolayers.
limitations
Directional flux in a transformed cell-line model is not a human fractional-absorption estimate.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Without ZIP14, the cultured intestinal barrier passed more manganese toward the blood-facing side.
primary_references
[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
tissue_or_cell_type
Caco-2 intestinal epithelial model
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 201–212
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ZIP14-deficient human Caco-2 Transwell monolayers · source_derived_draft · unverified_draft
### mn-trans-intestinal-zip14-absorptive ZIP14 deletion in human Caco-2 Transwell cultures increased apical-to-basolateral manganese transport. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Without ZIP14, the cultured intestinal barrier passed more manganese toward the blood-facing side. organism: Homo sapiens tissue_or_cell_type: Caco-2 intestinal epithelial model experimental_model: ZIP14-deficient human Caco-2 Transwell monolayers limitations: Directional flux in a transformed cell-line model is not a human fractional-absorption estimate. exposure: ZIP14-deficient versus control Caco-2 Transwell monolayers. cross_nutrient: false [mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
Complete structured claim and evidence
Liver-specific Zip14 knockout reduced liver manganese without producing manganese accumulation in other tissues under the reported normal conditions.
Mouse liver-specific Slc39a14 knockout genotype → Extrahepatic manganese accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Liver-specific Slc39a14 knockout mice
exposure
Liver-specific Slc39a14 knockout under normal study conditions.
limitations
A conditional negative result does not exclude a hepatic contribution when intestinal clearance is also impaired.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Liver ZIP14 loss alone did not reproduce whole-body manganese overload.
primary_references
[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
tissue_or_cell_type
Liver and extrahepatic tissues
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 214–225
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Liver-specific Slc39a14 knockout mice · source_derived_draft · unverified_draft
### mn-trans-hepatic-zip14-loss-no-systemic-overload Liver-specific Zip14 knockout reduced liver manganese without producing manganese accumulation in other tissues under the reported normal conditions. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Liver ZIP14 loss alone did not reproduce whole-body manganese overload. organism: Mus musculus tissue_or_cell_type: Liver and extrahepatic tissues experimental_model: Liver-specific Slc39a14 knockout mice limitations: A conditional negative result does not exclude a hepatic contribution when intestinal clearance is also impaired. exposure: Liver-specific Slc39a14 knockout under normal study conditions. cross_nutrient: false [mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
Complete structured claim and evidence
Intestine-specific Zip14 knockout increased liver and brain manganese in mice.
Mouse intestine-specific Slc39a14 knockout genotype → Systemic manganese accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Intestine-specific Slc39a14 knockout mice
exposure
Intestine-specific Slc39a14 knockout versus controls.
limitations
Liver and brain are specified outcomes; this statement does not imply every tissue or blood measure rose.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Intestinal ZIP14 loss increased manganese retained in distant tissues.
primary_references
[mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
tissue_or_cell_type
Intestine; manganese measured in liver and brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 227–238
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intestine-specific Slc39a14 knockout mice · source_derived_draft · unverified_draft
### mn-trans-intestinal-zip14-loss-tissue-mn Intestine-specific Zip14 knockout increased liver and brain manganese in mice. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intestinal ZIP14 loss increased manganese retained in distant tissues. organism: Mus musculus tissue_or_cell_type: Intestine; manganese measured in liver and brain experimental_model: Intestine-specific Slc39a14 knockout mice limitations: Liver and brain are specified outcomes; this statement does not imply every tissue or blood measure rose. exposure: Intestine-specific Slc39a14 knockout versus controls. cross_nutrient: false [mn-trans-31028174] The intestinal metal transporter ZIP14 maintains systemic manganese homeostasis. (2019). https://pubmed.ncbi.nlm.nih.gov/31028174/ DOI: 10.1074/jbc.ra119.008762
Complete structured claim and evidence
Whole-body Slc30a10 deficiency impaired systemic manganese excretion in mice.
Mouse whole-body Slc30a10 knockout genotype → Systemic manganese excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Whole-body and tissue-specific Slc30a10 knockout mice
exposure
Whole-body Slc30a10-deficient mice versus controls.
limitations
Genetic manganese retention is manganese excess, not nutrient deficiency.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Loss of Slc30a10 throughout the body reduced manganese clearance.
primary_references
[mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
tissue_or_cell_type
Hepatocytes and small-intestinal enterocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 240–251
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and tissue-specific Slc30a10 knockout mice · source_derived_draft · unverified_draft
### mn-trans-slc30a10-global-excretion Whole-body Slc30a10 deficiency impaired systemic manganese excretion in mice. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of Slc30a10 throughout the body reduced manganese clearance. organism: Mus musculus tissue_or_cell_type: Hepatocytes and small-intestinal enterocytes experimental_model: Whole-body and tissue-specific Slc30a10 knockout mice limitations: Genetic manganese retention is manganese excess, not nutrient deficiency. exposure: Whole-body Slc30a10-deficient mice versus controls. cross_nutrient: false [mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
Complete structured claim and evidence
Hepatic Slc30a10 deficiency impaired biliary manganese excretion in mice despite only minimal manganese excess.
Mouse hepatocyte-specific Slc30a10 knockout genotype → Biliary manganese excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Whole-body and tissue-specific Slc30a10 knockout mice
exposure
Liver-specific Slc30a10 deficiency versus controls.
limitations
Minimal systemic excess does not negate the measured biliary transport defect.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
The liver exporter supplied biliary clearance, while other routes limited whole-body accumulation.
primary_references
[mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
tissue_or_cell_type
Liver canalicular membrane and bile
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 253–264
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and tissue-specific Slc30a10 knockout mice · source_derived_draft · unverified_draft
### mn-trans-slc30a10-hepatic-excretion Hepatic Slc30a10 deficiency impaired biliary manganese excretion in mice despite only minimal manganese excess. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The liver exporter supplied biliary clearance, while other routes limited whole-body accumulation. organism: Mus musculus tissue_or_cell_type: Liver canalicular membrane and bile experimental_model: Whole-body and tissue-specific Slc30a10 knockout mice limitations: Minimal systemic excess does not negate the measured biliary transport defect. exposure: Liver-specific Slc30a10 deficiency versus controls. cross_nutrient: false [mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
Complete structured claim and evidence
Small-intestinal Slc30a10 deficiency impaired manganese export into the intestinal lumen in mice despite minimal manganese excess.
Mouse small-intestine Slc30a10 knockout genotype → Manganese export into the intestinal lumen source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Whole-body and tissue-specific Slc30a10 knockout mice
exposure
Small-intestine-specific Slc30a10 deficiency versus controls.
limitations
The cell-surface location is apical; net dietary absorption is a different measurement.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Enterocyte Slc30a10 helps secrete manganese directly into the intestine.
primary_references
[mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
tissue_or_cell_type
Small-intestinal enterocyte apical membrane and lumen
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 266–277
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and tissue-specific Slc30a10 knockout mice · source_derived_draft · unverified_draft
### mn-trans-slc30a10-intestinal-excretion Small-intestinal Slc30a10 deficiency impaired manganese export into the intestinal lumen in mice despite minimal manganese excess. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Enterocyte Slc30a10 helps secrete manganese directly into the intestine. organism: Mus musculus tissue_or_cell_type: Small-intestinal enterocyte apical membrane and lumen experimental_model: Whole-body and tissue-specific Slc30a10 knockout mice limitations: The cell-surface location is apical; net dietary absorption is a different measurement. exposure: Small-intestine-specific Slc30a10 deficiency versus controls. cross_nutrient: false [mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
Complete structured claim and evidence
Combined liver and small-intestine Slc30a10 deficiency caused manganese excess that was less severe than in whole-body deficient mice.
Mouse liver-and-small-intestine Slc30a10 double-knockout genotype → Systemic manganese accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Whole-body and tissue-specific Slc30a10 knockout mice
exposure
Liver-and-small-intestine Slc30a10 deficiency compared with controls and whole-body deficiency.
limitations
The residual difference suggests other sites or adaptation; it does not identify a specific untested tissue.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Deleting the liver and gut exporter did not reproduce the full severity of deleting it everywhere.
primary_references
[mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
tissue_or_cell_type
Hepatocytes and small-intestinal enterocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 279–290
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body and tissue-specific Slc30a10 knockout mice · source_derived_draft · unverified_draft
### mn-trans-slc30a10-double-versus-global Combined liver and small-intestine Slc30a10 deficiency caused manganese excess that was less severe than in whole-body deficient mice. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deleting the liver and gut exporter did not reproduce the full severity of deleting it everywhere. organism: Mus musculus tissue_or_cell_type: Hepatocytes and small-intestinal enterocytes experimental_model: Whole-body and tissue-specific Slc30a10 knockout mice limitations: The residual difference suggests other sites or adaptation; it does not identify a specific untested tissue. exposure: Liver-and-small-intestine Slc30a10 deficiency compared with controls and whole-body deficiency. cross_nutrient: false [mn-trans-31527311] Manganese transporter Slc30a10 controls physiological manganese excretion and toxicity. (2019). https://pubmed.ncbi.nlm.nih.gov/31527311/ DOI: 10.1172/jci129710
Complete structured claim and evidence
Mn(II) inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes.
Mn2+ → Cellular iron uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Mouse ZIP14 in RNA-injected Xenopus laevis oocytes
exposure
Radiolabeled Fe(II) uptake with added Mn(II).
limitations
Measured competition is assay-specific and does not establish dietary antagonism or ferric-iron transport.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mouse protein in Xenopus laevis oocytes
plain_language
Manganese reduced ferrous iron entry through ZIP14 in the assay.
primary_references
[mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 292–303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse ZIP14 in RNA-injected Xenopus laevis oocytes · source_derived_draft · unverified_draft
### mn-trans-zip14-mn-inhibits-fe Mn(II) inhibited mouse ZIP14-mediated Fe(II) uptake in Xenopus oocytes. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese reduced ferrous iron entry through ZIP14 in the assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Mouse ZIP14 in RNA-injected Xenopus laevis oocytes limitations: Measured competition is assay-specific and does not establish dietary antagonism or ferric-iron transport. exposure: Radiolabeled Fe(II) uptake with added Mn(II). cross_nutrient: true [mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
Fe(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions.
Ferrous iron → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Mouse ZIP14 in RNA-injected Xenopus laevis oocytes
exposure
2 micromolar radiolabeled Mn(II) with candidate inhibitor metal at 20 micromolar and 1 mM L-ascorbic acid; Figure 9B.
limitations
A tenfold molar competitor in a heterologous system is not a dietary competition threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mouse protein in Xenopus laevis oocytes
plain_language
Fe(II) competed with manganese entry through ZIP14 in this assay.
primary_references
[mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 305–316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse ZIP14 in RNA-injected Xenopus laevis oocytes · source_derived_draft · unverified_draft
### mn-trans-zip14-fe-inhibits-mn Fe(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Fe(II) competed with manganese entry through ZIP14 in this assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Mouse ZIP14 in RNA-injected Xenopus laevis oocytes limitations: A tenfold molar competitor in a heterologous system is not a dietary competition threshold. exposure: 2 micromolar radiolabeled Mn(II) with candidate inhibitor metal at 20 micromolar and 1 mM L-ascorbic acid; Figure 9B. cross_nutrient: true [mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
Zn(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions.
Zinc(II) ion → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Mouse ZIP14 in RNA-injected Xenopus laevis oocytes
exposure
2 micromolar radiolabeled Mn(II) with candidate inhibitor metal at 20 micromolar and 1 mM L-ascorbic acid; Figure 9B.
limitations
A tenfold molar competitor in a heterologous system is not a dietary competition threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mouse protein in Xenopus laevis oocytes
plain_language
Zn(II) competed with manganese entry through ZIP14 in this assay.
primary_references
[mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
tissue_or_cell_type
Oocyte plasma membrane
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 318–329
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse ZIP14 in RNA-injected Xenopus laevis oocytes · source_derived_draft · unverified_draft
### mn-trans-zip14-zn-inhibits-mn Zn(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zn(II) competed with manganese entry through ZIP14 in this assay. organism: Mouse protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Mouse ZIP14 in RNA-injected Xenopus laevis oocytes limitations: A tenfold molar competitor in a heterologous system is not a dietary competition threshold. exposure: 2 micromolar radiolabeled Mn(II) with candidate inhibitor metal at 20 micromolar and 1 mM L-ascorbic acid; Figure 9B. cross_nutrient: true [mn-trans-21653899] Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron. (2011). https://pubmed.ncbi.nlm.nih.gov/21653899/ DOI: 10.1152/ajpcell.00479.2010
Complete structured claim and evidence
ZIP14-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells.
Mouse ZIP14 (Slc39a14) → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture
exposure
ZIP14 siRNA versus controls during apical manganese exposure.
limitations
Cell culture supports an uptake contribution; it does not quantify in vivo urinary reabsorption or rank transporter contributions.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
ZIP14 helped kidney-derived cells take up manganese from their lumen-facing side.
primary_references
[mn-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
tissue_or_cell_type
Proximal-tubule epithelial cells, apical membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 331–342
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture · source_derived_draft · unverified_draft
### mn-trans-renal-zip14 ZIP14-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: ZIP14 helped kidney-derived cells take up manganese from their lumen-facing side. organism: Mus musculus tissue_or_cell_type: Proximal-tubule epithelial cells, apical membrane experimental_model: Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture limitations: Cell culture supports an uptake contribution; it does not quantify in vivo urinary reabsorption or rank transporter contributions. exposure: ZIP14 siRNA versus controls during apical manganese exposure. cross_nutrient: false [mn-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
Complete structured claim and evidence
DMT1-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells.
Mouse DMT1 (Slc11a2) → Cellular manganese uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture
exposure
DMT1 siRNA versus controls during apical manganese exposure.
limitations
Cell culture supports an uptake contribution; it does not quantify in vivo urinary reabsorption or rank transporter contributions.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
DMT1 helped kidney-derived cells take up manganese from their lumen-facing side.
primary_references
[mn-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
tissue_or_cell_type
Proximal-tubule epithelial cells, apical membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 344–355
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture · source_derived_draft · unverified_draft
### mn-trans-renal-dmt1 DMT1-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: DMT1 helped kidney-derived cells take up manganese from their lumen-facing side. organism: Mus musculus tissue_or_cell_type: Proximal-tubule epithelial cells, apical membrane experimental_model: Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture limitations: Cell culture supports an uptake contribution; it does not quantify in vivo urinary reabsorption or rank transporter contributions. exposure: DMT1 siRNA versus controls during apical manganese exposure. cross_nutrient: false [mn-trans-22534978] Roles of ZIP8, ZIP14, and DMT1 in transport of cadmium and manganese in mouse kidney proximal tubule cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22534978/ DOI: 10.1039/c2mt20024d
Complete structured claim and evidence
Combined intestinal and hepatic Zip14 deletion increased systemic manganese burden more than intestinal deletion alone in mice.
Mouse liver-and-intestine Slc39a14 double-knockout genotype → Systemic manganese accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Single- and double-tissue Slc39a14 knockout mice; ICP-MS
exposure
Intestine-and-liver double knockout versus single-tissue knockout and floxed controls.
limitations
Supports organ cooperation, not a universal claim that liver-only deletion causes systemic overload.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Liver ZIP14 became especially important when intestinal ZIP14 was also absent.
primary_references
[mn-trans-35742937] The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice. (2022). https://pubmed.ncbi.nlm.nih.gov/35742937/ DOI: 10.3390/ijms23126495
tissue_or_cell_type
Intestine, liver and systemic tissue manganese
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 357–368
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single- and double-tissue Slc39a14 knockout mice; ICP-MS · source_derived_draft · unverified_draft
### mn-trans-zip14-double-worsens-loading Combined intestinal and hepatic Zip14 deletion increased systemic manganese burden more than intestinal deletion alone in mice. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Liver ZIP14 became especially important when intestinal ZIP14 was also absent. organism: Mus musculus tissue_or_cell_type: Intestine, liver and systemic tissue manganese experimental_model: Single- and double-tissue Slc39a14 knockout mice; ICP-MS limitations: Supports organ cooperation, not a universal claim that liver-only deletion causes systemic overload. exposure: Intestine-and-liver double knockout versus single-tissue knockout and floxed controls. cross_nutrient: false [mn-trans-35742937] The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice. (2022). https://pubmed.ncbi.nlm.nih.gov/35742937/ DOI: 10.3390/ijms23126495
Complete structured claim and evidence
Cellular expression experiments identified human SLC30A10 as a cell-surface manganese efflux transporter.
Human manganese exporter SLC30A10 → Cellular manganese efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Human SLC30A10 expression in cellular assays
exposure
SLC30A10 expression and manganese transport assays.
limitations
The abstract summarizes multiple models; this claim concerns the cellular efflux function and does not infer a human treatment response.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Human transporter in cultured cells
plain_language
SLC30A10 moves manganese out of cells.
primary_references
[mn-trans-25319704] SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its intracellular trafficking and efflux activity. (2014). https://pubmed.ncbi.nlm.nih.gov/25319704/ DOI: 10.1523/jneurosci.2329-14.2014
tissue_or_cell_type
Cell surface
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 370–381
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC30A10 expression in cellular assays · source_derived_draft · unverified_draft
### mn-trans-slc30a10-cellular-efflux Cellular expression experiments identified human SLC30A10 as a cell-surface manganese efflux transporter. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: SLC30A10 moves manganese out of cells. organism: Human transporter in cultured cells tissue_or_cell_type: Cell surface experimental_model: Human SLC30A10 expression in cellular assays limitations: The abstract summarizes multiple models; this claim concerns the cellular efflux function and does not infer a human treatment response. exposure: SLC30A10 expression and manganese transport assays. cross_nutrient: false [mn-trans-25319704] SLC30A10 is a cell surface-localized manganese efflux transporter, and parkinsonism-causing mutations block its intracellular trafficking and efflux activity. (2014). https://pubmed.ncbi.nlm.nih.gov/25319704/ DOI: 10.1523/jneurosci.2329-14.2014
Complete structured claim and evidence
The Mn-bound inward-facing human SLC30A10 cryo-EM structure placed Mn(II) at a site coordinated by D40, N127, D248 and S252.
Human manganese exporter SLC30A10 → Mn2+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Cryo-EM of purified full-length human SLC30A10
exposure
Purified full-length human SLC30A10 in Mn-bound and Mn-free cryo-EM preparations.
limitations
A resolved binding site supports molecular recognition; individual steps in the proposed conformational transport cycle remain a structural model.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Human protein
plain_language
Four amino-acid residues form the transporter’s manganese-binding site.
primary_references
[mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7
tissue_or_cell_type
Purified membrane transporter
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 383–394
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of purified full-length human SLC30A10 · source_derived_draft · unverified_draft
### mn-trans-slc30a10-mn-coordination The Mn-bound inward-facing human SLC30A10 cryo-EM structure placed Mn(II) at a site coordinated by D40, N127, D248 and S252. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Four amino-acid residues form the transporter’s manganese-binding site. organism: Human protein tissue_or_cell_type: Purified membrane transporter experimental_model: Cryo-EM of purified full-length human SLC30A10 limitations: A resolved binding site supports molecular recognition; individual steps in the proposed conformational transport cycle remain a structural model. exposure: Purified full-length human SLC30A10 in Mn-bound and Mn-free cryo-EM preparations. cross_nutrient: false [mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7
Complete structured claim and evidence
Reconstituted human SLC30A10 transported Mn(II), while the same study detected no significant Zn(II), Ca(II) or Mg(II) transport under its tested conditions.
Human manganese exporter SLC30A10 → SLC30A10 divalent-metal transport selectivity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified full-length human SLC30A10 reconstituted into liposomes; Figure 1f and Supplementary Figure 3e-g
exposure
Separate MnCl2, ZnCl2, CaCl2 and MgCl2 proteoliposome transport tests.
limitations
The negative results are assay-bounded; they do not rule out calcium coupling under other gradients, establish exchange stoichiometry, or define a nutritional threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Human protein
plain_language
The purified transporter carried manganese without measurable transport of the three comparison metals in this assay.
primary_references
[mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7
tissue_or_cell_type
Proteoliposomes
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 396–407
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length human SLC30A10 reconstituted into liposomes; Figure 1f and Supplementary Figure 3e-g · source_derived_draft · unverified_draft
### mn-trans-slc30a10-metal-selectivity Reconstituted human SLC30A10 transported Mn(II), while the same study detected no significant Zn(II), Ca(II) or Mg(II) transport under its tested conditions. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The purified transporter carried manganese without measurable transport of the three comparison metals in this assay. organism: Human protein tissue_or_cell_type: Proteoliposomes experimental_model: Purified full-length human SLC30A10 reconstituted into liposomes; Figure 1f and Supplementary Figure 3e-g limitations: The negative results are assay-bounded; they do not rule out calcium coupling under other gradients, establish exchange stoichiometry, or define a nutritional threshold. exposure: Separate MnCl2, ZnCl2, CaCl2 and MgCl2 proteoliposome transport tests. cross_nutrient: true [mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7
Complete structured claim and evidence
Human SLC30A10 D40A lost manganese transport function in the HEK293T assay compared with wild-type SLC30A10.
Human SLC30A10 D40A mutant → Cellular manganese efflux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Site-directed SLC30A10 mutagenesis in HEK293T cells
exposure
D40A versus wild-type human SLC30A10 expression in HEK293T cells.
limitations
The functional mutant comparison does not establish treatment efficacy or a dietary manganese deficiency.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Changing aspartate 40 to alanine disabled the measured manganese transport function.
primary_references
[mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7
tissue_or_cell_type
HEK293T cellular manganese handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 409–420
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed SLC30A10 mutagenesis in HEK293T cells · source_derived_draft · unverified_draft
### mn-trans-slc30a10-d40a-transport-loss Human SLC30A10 D40A lost manganese transport function in the HEK293T assay compared with wild-type SLC30A10. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing aspartate 40 to alanine disabled the measured manganese transport function. organism: Homo sapiens tissue_or_cell_type: HEK293T cellular manganese handling experimental_model: Site-directed SLC30A10 mutagenesis in HEK293T cells limitations: The functional mutant comparison does not establish treatment efficacy or a dietary manganese deficiency. exposure: D40A versus wild-type human SLC30A10 expression in HEK293T cells. cross_nutrient: false [mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7
Complete structured claim and evidence
Neutron structures of human SOD2 captured Mn(III) and Mn(II) states with coupled changes in active-site protonation.
Human mitochondrial manganese superoxide dismutase / SOD2 → Mn(III)-bound human SOD2 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Redox-controlled neutron structures of human SOD2
exposure
Redox-controlled Mn(III) and Mn(II) crystals
limitations
Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
SOD2 changes manganese oxidation state as it transfers electrons and protons.
primary_references
[mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1
tissue_or_cell_type
Purified enzyme; mitochondrial-matrix protein
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 422–432
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Redox-controlled neutron structures of human SOD2 · source_derived_draft · unverified_draft
### mn-enz-sod2-redox-states Neutron structures of human SOD2 captured Mn(III) and Mn(II) states with coupled changes in active-site protonation. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD2 changes manganese oxidation state as it transfers electrons and protons. organism: Homo sapiens tissue_or_cell_type: Purified enzyme; mitochondrial-matrix protein experimental_model: Redox-controlled neutron structures of human SOD2 limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Redox-controlled Mn(III) and Mn(II) crystals [mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1
Complete structured claim and evidence
The human SOD2 active-site manganese is coordinated by His26, His74, His163, Asp159 and a water/hydroxide ligand in the structural model.
Mn2+ → Human mitochondrial manganese superoxide dismutase / SOD2 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Redox-controlled neutron structures of human SOD2
exposure
Redox-controlled Mn(III) and Mn(II) crystals
limitations
Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
A defined protein pocket holds manganese for SOD2 chemistry.
primary_references
[mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1
tissue_or_cell_type
Purified enzyme; mitochondrial-matrix protein
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 434–444
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Redox-controlled neutron structures of human SOD2 · source_derived_draft · unverified_draft
### mn-enz-sod2-coordination The human SOD2 active-site manganese is coordinated by His26, His74, His163, Asp159 and a water/hydroxide ligand in the structural model. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defined protein pocket holds manganese for SOD2 chemistry. organism: Homo sapiens tissue_or_cell_type: Purified enzyme; mitochondrial-matrix protein experimental_model: Redox-controlled neutron structures of human SOD2 limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Redox-controlled Mn(III) and Mn(II) crystals [mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1
Complete structured claim and evidence
Human SOD2 uses a Mn(III)/Mn(II) cycle to convert superoxide into oxygen and hydrogen peroxide.
Human mitochondrial manganese superoxide dismutase / SOD2 → Superoxide dismutation source_derived_draftungraded
Experimental context and source evidence
experimental_model
Redox-controlled neutron structures of human SOD2
exposure
Redox-controlled Mn(III) and Mn(II) crystals
limitations
Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
SOD2 removes superoxide; it produces hydrogen peroxide that requires further handling.
primary_references
[mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1
tissue_or_cell_type
Purified enzyme; mitochondrial-matrix protein
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 446–456
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Redox-controlled neutron structures of human SOD2 · source_derived_draft · unverified_draft
### mn-enz-sod2-superoxide Human SOD2 uses a Mn(III)/Mn(II) cycle to convert superoxide into oxygen and hydrogen peroxide. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD2 removes superoxide; it produces hydrogen peroxide that requires further handling. organism: Homo sapiens tissue_or_cell_type: Purified enzyme; mitochondrial-matrix protein experimental_model: Redox-controlled neutron structures of human SOD2 limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Redox-controlled Mn(III) and Mn(II) crystals [mn-enz-33824320] Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase. (2021). https://pubmed.ncbi.nlm.nih.gov/33824320/ DOI: 10.1038/s41467-021-22290-1
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
At 30 °C, more than half of human SOD2 purified from expressing yeast mitochondria was apoprotein, and that apoprotein could be fully activated by reconstitution.
Metal-free human SOD2 → Human SOD2 metallation source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human SOD2 expressed in Saccharomyces cerevisiae and purified from yeast mitochondria
exposure
Heterologous expression; metallation and reconstitution
limitations
Heterologous yeast expression, not endogenous human tissue. The indexed abstract does not specify a reconstitution dose.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Human protein in Saccharomyces cerevisiae
plain_language
Making SOD2 protein does not guarantee that it has loaded its metal.
primary_references
[mn-enz-22561997] Metallation state of human manganese superoxide dismutase expressed in Saccharomyces cerevisiae. (2012). https://pubmed.ncbi.nlm.nih.gov/22561997/ DOI: 10.1016/j.abb.2012.04.016
tissue_or_cell_type
Yeast mitochondria
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 471–481
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SOD2 expressed in Saccharomyces cerevisiae and purified from yeast mitochondria · source_derived_draft · unverified_draft
### mn-enz-sod2-yeast-apo At 30 °C, more than half of human SOD2 purified from expressing yeast mitochondria was apoprotein, and that apoprotein could be fully activated by reconstitution. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making SOD2 protein does not guarantee that it has loaded its metal. organism: Human protein in Saccharomyces cerevisiae tissue_or_cell_type: Yeast mitochondria experimental_model: Human SOD2 expressed in Saccharomyces cerevisiae and purified from yeast mitochondria limitations: Heterologous yeast expression, not endogenous human tissue. The indexed abstract does not specify a reconstitution dose. exposure: Heterologous expression; metallation and reconstitution [mn-enz-22561997] Metallation state of human manganese superoxide dismutase expressed in Saccharomyces cerevisiae. (2012). https://pubmed.ncbi.nlm.nih.gov/22561997/ DOI: 10.1016/j.abb.2012.04.016
Complete structured claim and evidence
Increasing yeast growth temperature increased both manganese content and activity of mitochondrially expressed human SOD2.
Human mitochondrial manganese superoxide dismutase / SOD2 → Human SOD2 metallation source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human SOD2 expressed in Saccharomyces cerevisiae and purified from yeast mitochondria
exposure
Heterologous expression; metallation and reconstitution
limitations
Human protein in yeast; this finding is not a recommendation to alter human body temperature.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Human protein in Saccharomyces cerevisiae
plain_language
SOD2 metal loading depended on the experimental expression conditions.
primary_references
[mn-enz-22561997] Metallation state of human manganese superoxide dismutase expressed in Saccharomyces cerevisiae. (2012). https://pubmed.ncbi.nlm.nih.gov/22561997/ DOI: 10.1016/j.abb.2012.04.016
tissue_or_cell_type
Yeast mitochondria
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 483–493
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SOD2 expressed in Saccharomyces cerevisiae and purified from yeast mitochondria · source_derived_draft · unverified_draft
### mn-enz-sod2-yeast-temperature Increasing yeast growth temperature increased both manganese content and activity of mitochondrially expressed human SOD2. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: SOD2 metal loading depended on the experimental expression conditions. organism: Human protein in Saccharomyces cerevisiae tissue_or_cell_type: Yeast mitochondria experimental_model: Human SOD2 expressed in Saccharomyces cerevisiae and purified from yeast mitochondria limitations: Human protein in yeast; this finding is not a recommendation to alter human body temperature. exposure: Heterologous expression; metallation and reconstitution [mn-enz-22561997] Metallation state of human manganese superoxide dismutase expressed in Saccharomyces cerevisiae. (2012). https://pubmed.ncbi.nlm.nih.gov/22561997/ DOI: 10.1016/j.abb.2012.04.016
Complete structured claim and evidence
Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments.
Iron-loaded human SOD2 → Iron-loaded SOD2 peroxidase activity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement.
experimental_model
Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments
exposure
Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets
limitations
Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens; Mus musculus
plain_language
Iron in the SOD2 site can change what the enzyme does.
primary_references
[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007
tissue_or_cell_type
Purified enzyme, cultured cells and mouse liver
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 495–506
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments · source_derived_draft · unverified_draft
### mn-enz-sod2-iron-peroxidase Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron in the SOD2 site can change what the enzyme does. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Purified enzyme, cultured cells and mouse liver experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred. exposure: Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets cross_nutrient: Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement. [mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007
Complete structured claim and evidence
Mice fed the lower-manganese diet for four weeks had approximately 30% of isolated liver Sod2 iron-loaded, versus negligible iron loading in controls.
Manganese → Iron-loaded mouse Sod2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Dietary Mn:Fe balance affected mouse Sod2 metal occupancy.
experimental_model
Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments
exposure
Four weeks of 40 ppm Mn/275 ppm Fe versus 150 ppm Mn/275 ppm Fe control.
limitations
Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Lower dietary manganese relative to iron changed liver Sod2 metal loading in mice.
primary_references
[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007
tissue_or_cell_type
Liver Sod2
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 508–519
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments · source_derived_draft · unverified_draft
### mn-enz-mouse-low-mn-iron-sod2 Mice fed the lower-manganese diet for four weeks had approximately 30% of isolated liver Sod2 iron-loaded, versus negligible iron loading in controls. Condition category: nutrient_deficiency nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower dietary manganese relative to iron changed liver Sod2 metal loading in mice. organism: Mus musculus tissue_or_cell_type: Liver Sod2 experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Four weeks of 40 ppm Mn/275 ppm Fe versus 150 ppm Mn/275 ppm Fe control. cross_nutrient: Dietary Mn:Fe balance affected mouse Sod2 metal occupancy. [mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007
Complete structured claim and evidence
After four weeks on the iron-enriched diet, nearly 80% of isolated mouse liver Sod2 was iron-loaded.
Iron → Iron-loaded mouse Sod2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron excess altered occupancy of a Mn enzyme.
experimental_model
Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments
exposure
Five-week-old male C57BL/6J mice; 2700 ppm Fe and 150 ppm Mn versus control 275 ppm Fe and 150 ppm Mn, four weeks.
limitations
Experimental iron excess, not iron deficiency or a human oral-dose equivalence.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
A high-iron mouse diet shifted Sod2 toward iron loading.
primary_references
[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007
tissue_or_cell_type
Liver Sod2
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 521–532
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments · source_derived_draft · unverified_draft
### mn-enz-mouse-high-fe-iron-sod2 After four weeks on the iron-enriched diet, nearly 80% of isolated mouse liver Sod2 was iron-loaded. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A high-iron mouse diet shifted Sod2 toward iron loading. organism: Mus musculus tissue_or_cell_type: Liver Sod2 experimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments limitations: Experimental iron excess, not iron deficiency or a human oral-dose equivalence. exposure: Five-week-old male C57BL/6J mice; 2700 ppm Fe and 150 ppm Mn versus control 275 ppm Fe and 150 ppm Mn, four weeks. cross_nutrient: Iron excess altered occupancy of a Mn enzyme. [mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007
Complete structured claim and evidence
Human ARG1 structures show a binuclear manganese site binding a boronate transition-state analogue, supporting metal stabilization of the arginine-hydrolysis transition state.
Mn2+ → Human arginase 1 / ARG1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
X-ray structures of human ARG1 with boronic-acid transition-state analogues
exposure
ABH and BEC inhibitor complexes
limitations
Transition-state analogue crystallography and author mechanistic inference; not direct nutritional manganese restriction.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
ARG1 holds two manganese ions at the site where arginine is hydrolyzed.
primary_references
[mn-enz-16141327] Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. (2005). https://pubmed.ncbi.nlm.nih.gov/16141327/ DOI: 10.1073/pnas.0504027102
tissue_or_cell_type
Purified ARG1
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 534–544
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of human ARG1 with boronic-acid transition-state analogues · source_derived_draft · unverified_draft
### mn-enz-arg1-binuclear-transition-state Human ARG1 structures show a binuclear manganese site binding a boronate transition-state analogue, supporting metal stabilization of the arginine-hydrolysis transition state. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: ARG1 holds two manganese ions at the site where arginine is hydrolyzed. organism: Homo sapiens protein tissue_or_cell_type: Purified ARG1 experimental_model: X-ray structures of human ARG1 with boronic-acid transition-state analogues limitations: Transition-state analogue crystallography and author mechanistic inference; not direct nutritional manganese restriction. exposure: ABH and BEC inhibitor complexes [mn-enz-16141327] Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. (2005). https://pubmed.ncbi.nlm.nih.gov/16141327/ DOI: 10.1073/pnas.0504027102
Complete structured claim and evidence
For reconstituted human ARG1, turnover and catalytic efficiency ranked Mn(II) > Ni(II) ≈ Co(II) ≫ Zn(II).
Mn2+ → Human arginase 1 / ARG1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc and cobalt substitutions were less effective than Mn; in-vitro substitution does not establish nutritional equivalence.
experimental_model
Metal-substitution crystallography and kinetics of purified human ARG1
exposure
Non-native metal reconstitution or added zinc
limitations
Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
Manganese gave the most efficient ARG1 catalysis in this comparison.
primary_references
[mn-enz-23061982] Structure and function of non-native metal clusters in human arginase I. (2012). https://pubmed.ncbi.nlm.nih.gov/23061982/ DOI: 10.1021/bi301145n
tissue_or_cell_type
Purified enzyme
Manganese: enzyme cofactors, glycosylation, transport 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 · Metal-substitution crystallography and kinetics of purified human ARG1 · source_derived_draft · unverified_draft
### mn-enz-arg1-manganese-optimum For reconstituted human ARG1, turnover and catalytic efficiency ranked Mn(II) > Ni(II) ≈ Co(II) ≫ Zn(II). Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese gave the most efficient ARG1 catalysis in this comparison. organism: Homo sapiens protein tissue_or_cell_type: Purified enzyme experimental_model: Metal-substitution crystallography and kinetics of purified human ARG1 limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Non-native metal reconstitution or added zinc cross_nutrient: Zinc and cobalt substitutions were less effective than Mn; in-vitro substitution does not establish nutritional equivalence. [mn-enz-23061982] Structure and function of non-native metal clusters in human arginase I. (2012). https://pubmed.ncbi.nlm.nih.gov/23061982/ DOI: 10.1021/bi301145n
Complete structured claim and evidence
Added Zn(II) bound the H141/E277 region of manganese-loaded human ARG1, revealing a structural basis for zinc inhibition.
Zinc(II) ion → Human arginase 1 / ARG1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zn inhibition of a Mn enzyme was structurally measured in purified protein; no dietary threshold.
experimental_model
Metal-substitution crystallography and kinetics of purified human ARG1
exposure
Non-native metal reconstitution or added zinc
limitations
Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
Zinc can inhibit purified manganese-loaded ARG1 at an additional site.
primary_references
[mn-enz-23061982] Structure and function of non-native metal clusters in human arginase I. (2012). https://pubmed.ncbi.nlm.nih.gov/23061982/ DOI: 10.1021/bi301145n
tissue_or_cell_type
Purified enzyme
Manganese: enzyme cofactors, glycosylation, transport 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 · Metal-substitution crystallography and kinetics of purified human ARG1 · source_derived_draft · unverified_draft
### mn-enz-arg1-zinc-inhibition Added Zn(II) bound the H141/E277 region of manganese-loaded human ARG1, revealing a structural basis for zinc inhibition. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc can inhibit purified manganese-loaded ARG1 at an additional site. organism: Homo sapiens protein tissue_or_cell_type: Purified enzyme experimental_model: Metal-substitution crystallography and kinetics of purified human ARG1 limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Non-native metal reconstitution or added zinc cross_nutrient: Zn inhibition of a Mn enzyme was structurally measured in purified protein; no dietary threshold. [mn-enz-23061982] Structure and function of non-native metal clusters in human arginase I. (2012). https://pubmed.ncbi.nlm.nih.gov/23061982/ DOI: 10.1021/bi301145n
Complete structured claim and evidence
Purified recombinant human ARG2 catalyzes arginine hydrolysis to ornithine and urea.
Human arginase 2 / ARG2 → L-Arginine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human ARG2 expressed in E. coli and purified
exposure
Substrate/product kinetics
limitations
Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
ARG2 breaks arginine into ornithine and urea.
primary_references
[mn-enz-11370664] Expression, purification, and characterization of human type II arginase. (2001). https://pubmed.ncbi.nlm.nih.gov/11370664/ DOI: 10.1006/abbi.2001.2324
tissue_or_cell_type
Purified ARG2
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 572–582
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human ARG2 expressed in E. coli and purified · source_derived_draft · unverified_draft
### mn-enz-arg2-hydrolysis Purified recombinant human ARG2 catalyzes arginine hydrolysis to ornithine and urea. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: ARG2 breaks arginine into ornithine and urea. organism: Homo sapiens protein tissue_or_cell_type: Purified ARG2 experimental_model: Recombinant human ARG2 expressed in E. coli and purified limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Substrate/product kinetics [mn-enz-11370664] Expression, purification, and characterization of human type II arginase. (2001). https://pubmed.ncbi.nlm.nih.gov/11370664/ DOI: 10.1006/abbi.2001.2324
Complete structured claim and evidence
The active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis.
Mn2+ → Human arginase 2 / ARG2 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Crystal structure of active truncated human ARG2 with transition-state analogue
exposure
Boronic-acid inhibitor complex; 2.7-A structure
limitations
Structural consistency with the proposed mechanism; truncated active recombinant human ARG2 with inhibitor, not direct dietary manganese perturbation.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
Two manganese ions help ARG2 activate the water-derived attacking group.
primary_references
[mn-enz-12859189] Human arginase II: crystal structure and physiological role in male and female sexual arousal. (2003). https://pubmed.ncbi.nlm.nih.gov/12859189/ DOI: 10.1021/bi034340j
tissue_or_cell_type
Purified ARG2
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 584–594
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure of active truncated human ARG2 with transition-state analogue · source_derived_draft · unverified_draft
### mn-enz-arg2-metal-hydroxide The active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two manganese ions help ARG2 activate the water-derived attacking group. organism: Homo sapiens protein tissue_or_cell_type: Purified ARG2 experimental_model: Crystal structure of active truncated human ARG2 with transition-state analogue limitations: Structural consistency with the proposed mechanism; truncated active recombinant human ARG2 with inhibitor, not direct dietary manganese perturbation. exposure: Boronic-acid inhibitor complex; 2.7-A structure [mn-enz-12859189] Human arginase II: crystal structure and physiological role in male and female sexual arousal. (2003). https://pubmed.ncbi.nlm.nih.gov/12859189/ DOI: 10.1021/bi034340j
Complete structured claim and evidence
Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine.
Glutamine synthetase / GLUL → L-Glutamine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human GLUL ligand-complex crystal structures; canine apoenzyme comparison
exposure
ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes
limitations
Reaction identity does not determine the predominant metal in living human brain.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
GLUL combines glutamate and ammonia using ATP.
primary_references
[mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
tissue_or_cell_type
Purified GLUL
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 596–606
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLUL ligand-complex crystal structures; canine apoenzyme comparison · source_derived_draft · unverified_draft
### mn-enz-glul-reaction Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: GLUL combines glutamate and ammonia using ATP. organism: Homo sapiens protein tissue_or_cell_type: Purified GLUL experimental_model: Human GLUL ligand-complex crystal structures; canine apoenzyme comparison limitations: Reaction identity does not determine the predominant metal in living human brain. exposure: ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
Complete structured claim and evidence
Human GLUL crystal structures contained Mn with ADP/phosphate or ADP/phosphorylated methionine-sulfoximine.
Mn2+ → Glutamine synthetase / GLUL source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human GLUL ligand-complex crystal structures; canine apoenzyme comparison
exposure
ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes
limitations
Crystallographic Mn binding does not establish exclusive Mn dependence or endogenous human brain metal occupancy.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
Human GLUL can bind manganese in the reported structural complexes.
primary_references
[mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
tissue_or_cell_type
Purified GLUL
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 608–618
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLUL ligand-complex crystal structures; canine apoenzyme comparison · source_derived_draft · unverified_draft
### mn-enz-glul-mn-crystals Human GLUL crystal structures contained Mn with ADP/phosphate or ADP/phosphorylated methionine-sulfoximine. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human GLUL can bind manganese in the reported structural complexes. organism: Homo sapiens protein tissue_or_cell_type: Purified GLUL experimental_model: Human GLUL ligand-complex crystal structures; canine apoenzyme comparison limitations: Crystallographic Mn binding does not establish exclusive Mn dependence or endogenous human brain metal occupancy. exposure: ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
Complete structured claim and evidence
Ovine brain GLUL assays showed optimal Mg:ATP at 2:1 and Mn:ATP at 1:1, with different reported pH optima of 7.5 and 5.0, respectively.
Ovine glutamine synthetase / GLUL → Glutamine synthetase metal-dependent assay activity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mn and Mg can support activity in vitro, with distinct metal:ATP ratios and pH conditions.
experimental_model
Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements
exposure
Mn(II) and Mg(II) titrations; binding and tissue metal measurements
limitations
Different assay optima are not evidence that Mn is the preferred cofactor at physiological brain pH.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Ovis aries
plain_language
Magnesium and manganese supported GLUL under different assay conditions.
primary_references
[mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011
tissue_or_cell_type
Brain-derived purified enzyme
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 620–631
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements · source_derived_draft · unverified_draft
### mn-enz-ovine-glul-metal-kinetics Ovine brain GLUL assays showed optimal Mg:ATP at 2:1 and Mn:ATP at 1:1, with different reported pH optima of 7.5 and 5.0, respectively. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and manganese supported GLUL under different assay conditions. organism: Ovis aries tissue_or_cell_type: Brain-derived purified enzyme experimental_model: Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements limitations: Different assay optima are not evidence that Mn is the preferred cofactor at physiological brain pH. exposure: Mn(II) and Mg(II) titrations; binding and tissue metal measurements cross_nutrient: Mn and Mg can support activity in vitro, with distinct metal:ATP ratios and pH conditions. [mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011
Complete structured claim and evidence
From ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo.
Mn2+ → Ovine glutamine synthetase / GLUL source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Published inference about Mn versus Mg native occupancy; paired with the competing 1986 cofactor-trapping interpretation.
experimental_model
Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements
exposure
Mn(II) and Mg(II) titrations; binding and tissue metal measurements
limitations
Author inference; not a universal human GLUL cofactor assignment. Contradicted by a later overlapping ovine/bovine study using endogenous-cofactor trapping.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Ovis aries
plain_language
One primary study proposed manganese as the native sheep-brain GLUL metal.
primary_references
[mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011
tissue_or_cell_type
Brain-derived purified enzyme
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 633–644
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements · source_derived_draft · unverified_draft
### mn-enz-ovine-glul-native-mn-interpretation From ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: One primary study proposed manganese as the native sheep-brain GLUL metal. organism: Ovis aries tissue_or_cell_type: Brain-derived purified enzyme experimental_model: Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements limitations: Author inference; not a universal human GLUL cofactor assignment. Contradicted by a later overlapping ovine/bovine study using endogenous-cofactor trapping. exposure: Mn(II) and Mg(II) titrations; binding and tissue metal measurements cross_nutrient: Published inference about Mn versus Mg native occupancy; paired with the competing 1986 cofactor-trapping interpretation. [mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011
Complete structured claim and evidence
Cofactor-trapped GLUL from bovine or ovine brain contained 1.5±0.2 Mg per subunit and less than 0.05 Mn per subunit.
Mg2+ → Ovine glutamine synthetase / GLUL source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct native-metal trapping distinguishes Mg occupancy from Mn-supported activity in vitro.
experimental_model
Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase
exposure
Methionine sulfoximine phosphate/ADP cofactor trapping
limitations
Extraction with methionine sulfoximine phosphate and ADP; bovine/ovine brain, not direct living human brain measurement.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Bos taurus; Ovis aries
plain_language
A cofactor-trapping study recovered mainly magnesium from brain GLUL.
primary_references
[mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0
tissue_or_cell_type
Brain extracts and purified enzyme
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 646–657
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase · source_derived_draft · unverified_draft
### mn-enz-brain-glul-cofactor-trapping Cofactor-trapped GLUL from bovine or ovine brain contained 1.5±0.2 Mg per subunit and less than 0.05 Mn per subunit. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cofactor-trapping study recovered mainly magnesium from brain GLUL. organism: Bos taurus; Ovis aries tissue_or_cell_type: Brain extracts and purified enzyme experimental_model: Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase limitations: Extraction with methionine sulfoximine phosphate and ADP; bovine/ovine brain, not direct living human brain measurement. exposure: Methionine sulfoximine phosphate/ADP cofactor trapping cross_nutrient: Direct native-metal trapping distinguishes Mg occupancy from Mn-supported activity in vitro. [mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0
Complete structured claim and evidence
The 1986 cofactor-trapping study concluded that Mg, rather than Mn, appears to be bound to bovine/ovine brain GLUL in vivo, although either metal supports assays.
Mg2+ → Ovine glutamine synthetase / GLUL source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Competing primary interpretation of native GLUL Mn versus Mg identity.
experimental_model
Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase
exposure
Methionine sulfoximine phosphate/ADP cofactor trapping
limitations
Author interpretation of extracted enzyme; overlaps the ovine brain question in 1982, with different methods.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Bos taurus; Ovis aries
plain_language
Another primary study supported magnesium as the native brain GLUL metal.
primary_references
[mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0
tissue_or_cell_type
Brain extracts and purified enzyme
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 659–670
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase · source_derived_draft · unverified_draft
### mn-enz-brain-glul-native-mg-interpretation The 1986 cofactor-trapping study concluded that Mg, rather than Mn, appears to be bound to bovine/ovine brain GLUL in vivo, although either metal supports assays. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another primary study supported magnesium as the native brain GLUL metal. organism: Bos taurus; Ovis aries tissue_or_cell_type: Brain extracts and purified enzyme experimental_model: Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase limitations: Author interpretation of extracted enzyme; overlaps the ovine brain question in 1982, with different methods. exposure: Methionine sulfoximine phosphate/ADP cofactor trapping cross_nutrient: Competing primary interpretation of native GLUL Mn versus Mg identity. [mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0
Complete structured claim and evidence
Mg-depleted rats had lower manganese concentrations in plasma and every sampled tissue except adrenal glands and blood.
Magnesium → Rat tissue manganese concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Mg depletion reduced Mn status in this rat dietary model.
experimental_model
Forty 3-week-old male Wistar rats assigned Mg-deficient or control diets for two weeks
exposure
Mg-deficient versus normal synthetic diet for two weeks, starting at three weeks of age.
limitations
Dietary Mg perturbation; association of Mn with PC does not isolate Mn as causal mediator.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Rattus norvegicus
plain_language
Magnesium depletion changed manganese status in rats.
primary_references
[mn-enz-8773758] Tissue manganese levels and liver pyruvate carboxylase activity in magnesium-deficient rats. (1996). https://pubmed.ncbi.nlm.nih.gov/8773758/ DOI: 10.1007/bf02789459
tissue_or_cell_type
Liver crude mitochondrial fraction; tissues and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 672–683
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Forty 3-week-old male Wistar rats assigned Mg-deficient or control diets for two weeks · source_derived_draft · unverified_draft
### mn-enz-mg-depletion-mn-status Mg-depleted rats had lower manganese concentrations in plasma and every sampled tissue except adrenal glands and blood. Condition category: nutrient_deficiency nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium depletion changed manganese status in rats. organism: Rattus norvegicus tissue_or_cell_type: Liver crude mitochondrial fraction; tissues and plasma experimental_model: Forty 3-week-old male Wistar rats assigned Mg-deficient or control diets for two weeks limitations: Dietary Mg perturbation; association of Mn with PC does not isolate Mn as causal mediator. exposure: Mg-deficient versus normal synthetic diet for two weeks, starting at three weeks of age. cross_nutrient: Mg depletion reduced Mn status in this rat dietary model. [mn-enz-8773758] Tissue manganese levels and liver pyruvate carboxylase activity in magnesium-deficient rats. (1996). https://pubmed.ncbi.nlm.nih.gov/8773758/ DOI: 10.1007/bf02789459
Complete structured claim and evidence
Mg depletion decreased liver crude-mitochondrial pyruvate-carboxylase activity; activity correlated positively with liver Mn concentration.
Magnesium → Rat hepatic pyruvate carboxylase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Mg–Mn association with PC function; no demonstration of Mn-mediated rescue.
experimental_model
Forty 3-week-old male Wistar rats assigned Mg-deficient or control diets for two weeks
exposure
Mg-deficient versus normal synthetic diet for two weeks, starting at three weeks of age.
limitations
Correlation does not establish direct Mn causation. No human PC metal requirement or biotin-rescue claim is inferred.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Rattus norvegicus
plain_language
Lower PC activity accompanied the altered manganese status during rat magnesium depletion.
primary_references
[mn-enz-8773758] Tissue manganese levels and liver pyruvate carboxylase activity in magnesium-deficient rats. (1996). https://pubmed.ncbi.nlm.nih.gov/8773758/ DOI: 10.1007/bf02789459
tissue_or_cell_type
Liver crude mitochondrial fraction; tissues and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 685–696
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Forty 3-week-old male Wistar rats assigned Mg-deficient or control diets for two weeks · source_derived_draft · unverified_draft
### mn-enz-mg-depletion-pc Mg depletion decreased liver crude-mitochondrial pyruvate-carboxylase activity; activity correlated positively with liver Mn concentration. Condition category: nutrient_deficiency nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower PC activity accompanied the altered manganese status during rat magnesium depletion. organism: Rattus norvegicus tissue_or_cell_type: Liver crude mitochondrial fraction; tissues and plasma experimental_model: Forty 3-week-old male Wistar rats assigned Mg-deficient or control diets for two weeks limitations: Correlation does not establish direct Mn causation. No human PC metal requirement or biotin-rescue claim is inferred. exposure: Mg-deficient versus normal synthetic diet for two weeks, starting at three weeks of age. cross_nutrient: Mg–Mn association with PC function; no demonstration of Mn-mediated rescue. [mn-enz-8773758] Tissue manganese levels and liver pyruvate carboxylase activity in magnesium-deficient rats. (1996). https://pubmed.ncbi.nlm.nih.gov/8773758/ DOI: 10.1007/bf02789459
Complete structured claim and evidence
Human SPCA1a couples its ATPase cycle to manganese movement from cytosol into the Golgi lumen.
Human SPCA1 isoform a → Manganese import into the Golgi lumen source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Secretory pathway calcium/manganese ATPase 1 (parent_protein); Manganese(II) ion (transported_ion); Adenosine triphosphate (energy_substrate); Golgi apparatus (destination)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/spca2023.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "start_char": 0, "end_char": 1276, "text_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "text_characters": 1276}
experimental_model
Cryo-EM of purified human SPCA1a with ATP and divalent ions
exposure
ATP/Ca2+, ATP/Mn2+ and phosphorylated metal-free structural states.
limitations
Structural states explain the transport cycle but do not supply a dietary requirement or prove that calcium supplementation impairs manganese delivery.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
An ATP-powered pump delivers manganese to the Golgi.
primary_references
[mn-gly-spca2023] Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus. (2023). https://pubmed.ncbi.nlm.nih.gov/36867705/ DOI: 10.1126/sciadv.add9742
tissue_or_cell_type
Golgi membrane transport protein
transport_effect
raises Recorded as manganese movement from cytosol into the Golgi lumen.
transport_pool
the Golgi lumen Recorded as manganese movement from cytosol into the Golgi lumen.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 698–710
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of purified human SPCA1a with ATP and divalent ions · source_derived_draft · unverified_draft
### mn-gly-spca-manganese Human SPCA1a couples its ATPase cycle to manganese movement from cytosol into the Golgi lumen. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An ATP-powered pump delivers manganese to the Golgi. organism: Homo sapiens tissue_or_cell_type: Golgi membrane transport protein experimental_model: Cryo-EM of purified human SPCA1a with ATP and divalent ions limitations: Structural states explain the transport cycle but do not supply a dietary requirement or prove that calcium supplementation impairs manganese delivery. exposure: ATP/Ca2+, ATP/Mn2+ and phosphorylated metal-free structural states. cross_nutrient: Secretory pathway calcium/manganese ATPase 1 (parent_protein); Manganese(II) ion (transported_ion); Adenosine triphosphate (energy_substrate); Golgi apparatus (destination) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/spca2023.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "start_char": 0, "end_char": 1276, "text_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "text_characters": 1276} [mn-gly-spca2023] Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus. (2023). https://pubmed.ncbi.nlm.nih.gov/36867705/ DOI: 10.1126/sciadv.add9742
Complete structured claim and evidence
Human SPCA1a also transports calcium; calcium and manganese occupy the same transmembrane pocket in the respective structures.
Human SPCA1 isoform a → Calcium import into the Golgi lumen source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
calcium ion (transported_ion); Manganese(II) ion (alternative_ion); Adenosine triphosphate (energy_substrate); Golgi apparatus (destination)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/spca2023.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "start_char": 0, "end_char": 1276, "text_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "text_characters": 1276}
experimental_model
Cryo-EM of purified human SPCA1a with ATP and divalent ions
exposure
ATP/Ca2+, ATP/Mn2+ and phosphorylated metal-free structural states.
limitations
Structural states explain the transport cycle but do not supply a dietary requirement or prove that calcium supplementation impairs manganese delivery.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The same pump handles calcium and manganese through a shared site.
primary_references
[mn-gly-spca2023] Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus. (2023). https://pubmed.ncbi.nlm.nih.gov/36867705/ DOI: 10.1126/sciadv.add9742
tissue_or_cell_type
Golgi membrane transport protein
transport_effect
raises The object already names import into the Golgi lumen.
transport_pool
the Golgi lumen The object already names import into the Golgi lumen.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 712–724
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of purified human SPCA1a with ATP and divalent ions · source_derived_draft · unverified_draft
### mn-gly-spca-calcium Human SPCA1a also transports calcium; calcium and manganese occupy the same transmembrane pocket in the respective structures. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same pump handles calcium and manganese through a shared site. organism: Homo sapiens tissue_or_cell_type: Golgi membrane transport protein experimental_model: Cryo-EM of purified human SPCA1a with ATP and divalent ions limitations: Structural states explain the transport cycle but do not supply a dietary requirement or prove that calcium supplementation impairs manganese delivery. exposure: ATP/Ca2+, ATP/Mn2+ and phosphorylated metal-free structural states. cross_nutrient: calcium ion (transported_ion); Manganese(II) ion (alternative_ion); Adenosine triphosphate (energy_substrate); Golgi apparatus (destination) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/spca2023.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "start_char": 0, "end_char": 1276, "text_sha256": "06a3eac4cc4e989b9195bdb14847c868ddaa68935a12f2d5c5f50a1a47259fb8", "text_characters": 1276} [mn-gly-spca2023] Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus. (2023). https://pubmed.ncbi.nlm.nih.gov/36867705/ DOI: 10.1126/sciadv.add9742
Complete structured claim and evidence
In the manganese-containing bovine B4GALT1 complex, donor binding reorganized residues 345–365 and Trp314, creating the sugar-acceptor pocket.
UDP-galactose → B4GALT1 sugar-acceptor site formation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Bovine beta-1,4-galactosyltransferase 1 (enzyme); Manganese(II) ion (bound_cofactor)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/b4galt2002.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "343551452a01a412f22e9b1ca6765817b1a192a23107954294032effe3f0904b", "start_char": 0, "end_char": 1632, "text_sha256": "343551452a01a412f22e9b1ca6765817b1a192a23107954294032effe3f0904b", "text_characters": 1632}
experimental_model
2.8-angstrom crystal structure of the bovine B4GALT1 catalytic domain
exposure
UDP-galactose and MnCl2 in the crystallized complex.
limitations
This is bovine catalytic-domain evidence. A donor-bound structure does not determine human tissue manganese occupancy or clinical substrate limitation.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Bos taurus
plain_language
Loading the donor sugar helped prepare the enzyme to receive its target sugar chain.
primary_references
[mn-gly-b4galt2002] Crystal structure of beta1,4-galactosyltransferase complex with UDP-Gal reveals an oligosaccharide acceptor binding site. (2002). https://pubmed.ncbi.nlm.nih.gov/12051854/ DOI: 10.1016/s0022-2836(02)00020-7
tissue_or_cell_type
Purified recombinant enzyme
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 726–738
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 2.8-angstrom crystal structure of the bovine B4GALT1 catalytic domain · source_derived_draft · unverified_draft
### mn-gly-b4galt-donor-conformation In the manganese-containing bovine B4GALT1 complex, donor binding reorganized residues 345–365 and Trp314, creating the sugar-acceptor pocket. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loading the donor sugar helped prepare the enzyme to receive its target sugar chain. organism: Bos taurus tissue_or_cell_type: Purified recombinant enzyme experimental_model: 2.8-angstrom crystal structure of the bovine B4GALT1 catalytic domain limitations: This is bovine catalytic-domain evidence. A donor-bound structure does not determine human tissue manganese occupancy or clinical substrate limitation. exposure: UDP-galactose and MnCl2 in the crystallized complex. cross_nutrient: Bovine beta-1,4-galactosyltransferase 1 (enzyme); Manganese(II) ion (bound_cofactor) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/b4galt2002.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "343551452a01a412f22e9b1ca6765817b1a192a23107954294032effe3f0904b", "start_char": 0, "end_char": 1632, "text_sha256": "343551452a01a412f22e9b1ca6765817b1a192a23107954294032effe3f0904b", "text_characters": 1632} [mn-gly-b4galt2002] Crystal structure of beta1,4-galactosyltransferase complex with UDP-Gal reveals an oligosaccharide acceptor binding site. (2002). https://pubmed.ncbi.nlm.nih.gov/12051854/ DOI: 10.1016/s0022-2836(02)00020-7
Complete structured claim and evidence
Manganese supplementation restored glycosylation in the TMEM165-depleted mammalian-cell experiments.
Mn2+ → Golgi protein glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
TMEM165 Golgi cation-homeostasis protein (affected_protein); Golgi apparatus (affected_compartment)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/potelle2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "start_char": 0, "end_char": 1190, "text_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "text_characters": 1190}
experimental_model
TMEM165-depleted mammalian cells and separate yeast Gdt1 loss experiments
exposure
Mn2+ supplementation of depleted cells.
limitations
These records describe the mammalian-cell arm. The indexed abstract does not specify every line, dose or treatment duration; rescue supports a homeostasis role rather than establishing a transport stoichiometry.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mammalian cell model; yeast comparison
plain_language
More available manganese could compensate for this Golgi-handling defect in cells.
primary_references
[mn-gly-potelle2016] Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis. (2016). https://pubmed.ncbi.nlm.nih.gov/27008884/ DOI: 10.1093/hmg/ddw026
tissue_or_cell_type
Golgi glycosylation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 740–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-depleted mammalian cells and separate yeast Gdt1 loss experiments · source_derived_draft · unverified_draft
### mn-gly-tmem165-mn-rescue Manganese supplementation restored glycosylation in the TMEM165-depleted mammalian-cell experiments. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: More available manganese could compensate for this Golgi-handling defect in cells. organism: Mammalian cell model; yeast comparison tissue_or_cell_type: Golgi glycosylation experimental_model: TMEM165-depleted mammalian cells and separate yeast Gdt1 loss experiments limitations: These records describe the mammalian-cell arm. The indexed abstract does not specify every line, dose or treatment duration; rescue supports a homeostasis role rather than establishing a transport stoichiometry. exposure: Mn2+ supplementation of depleted cells. cross_nutrient: TMEM165 Golgi cation-homeostasis protein (affected_protein); Golgi apparatus (affected_compartment) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/potelle2016.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "start_char": 0, "end_char": 1190, "text_sha256": "e1845bfbdbb15370fd1375534464f61aa6e5674cc4129b6f0992d9a022882cc3", "text_characters": 1190} [mn-gly-potelle2016] Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis. (2016). https://pubmed.ncbi.nlm.nih.gov/27008884/ DOI: 10.1093/hmg/ddw026
Complete structured claim and evidence
MnCl2 restored the measured N-glycosylation phenotype in TMEM165-knockout HEK cells.
Manganese(II) chloride → LAMP2 N-linked glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Manganese(II) ion (supplied_ion); Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 and TGN46 electrophoretic profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092}
experimental_model
Control and TMEM165-knockout HEK293 glycosylation assays
exposure
Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours.
limitations
Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Manganese improved the N-linked sugar-chain readout.
primary_references
[mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
tissue_or_cell_type
HEK293 cells and secretory glycoproteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 754–766
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft
### mn-gly-mn-n-linked-rescue MnCl2 restored the measured N-glycosylation phenotype in TMEM165-knockout HEK cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese improved the N-linked sugar-chain readout. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours. cross_nutrient: Manganese(II) ion (supplied_ion); Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 and TGN46 electrophoretic profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
Complete structured claim and evidence
MnCl2 restored the measured O-linked glycosylation defects in TMEM165-knockout HEK cells.
Manganese(II) chloride → Mucin-type O-linked glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Manganese(II) ion (supplied_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; lectin staining and benzyl-GalNAc mass-spectrometry profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 24441, "end_char": 25329, "text_sha256": "40d6513f6782e8f624ca1d04f64d8153282e2beed8877766a60140128e1b438d", "text_characters": 888}
experimental_model
Control and TMEM165-knockout HEK293 glycosylation assays
exposure
Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days.
limitations
Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Manganese also improved a different class of sugar chains.
primary_references
[mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
tissue_or_cell_type
HEK293 cells and secretory glycoproteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 768–780
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft
### mn-gly-mn-o-linked-rescue MnCl2 restored the measured O-linked glycosylation defects in TMEM165-knockout HEK cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese also improved a different class of sugar chains. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days. cross_nutrient: Manganese(II) ion (supplied_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; lectin staining and benzyl-GalNAc mass-spectrometry profiles", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 24441, "end_char": 25329, "text_sha256": "40d6513f6782e8f624ca1d04f64d8153282e2beed8877766a60140128e1b438d", "text_characters": 888} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
Complete structured claim and evidence
MnCl2 restored the decorin glycosaminoglycan readout in mouse Tmem165-knockout ATDC5 cells.
Manganese(II) chloride → Decorin glycosaminoglycan modification source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Manganese(II) ion (supplied_ion); Mouse TMEM165 (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 5; decorin migration", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 25939, "end_char": 27086, "text_sha256": "d94138936b018635104317fedba6c1298f0d54c6cd7b3f578b60000cea925bf5", "text_characters": 1147}
experimental_model
Tmem165-knockout mouse ATDC5 chondrogenic cells
exposure
Decorin-transfected ATDC5 cells: 1 micromolar MnCl2, 1 millimolar galactose or 1 millimolar xylose for 36 hours.
limitations
Decorin chondroitin-sulfate elongation in mouse chondrogenic cells. This is a separate model from the human HEK N/O-glycosylation assays and does not establish clinical cartilage rescue.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Manganese restored the measured sugar-chain modification on a matrix proteoglycan.
primary_references
[mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
tissue_or_cell_type
Mouse chondrogenic ATDC5 cells and secreted decorin
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 782–794
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tmem165-knockout mouse ATDC5 chondrogenic cells · source_derived_draft · unverified_draft
### mn-gly-mn-gag-rescue MnCl2 restored the decorin glycosaminoglycan readout in mouse Tmem165-knockout ATDC5 cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese restored the measured sugar-chain modification on a matrix proteoglycan. organism: Mus musculus tissue_or_cell_type: Mouse chondrogenic ATDC5 cells and secreted decorin experimental_model: Tmem165-knockout mouse ATDC5 chondrogenic cells limitations: Decorin chondroitin-sulfate elongation in mouse chondrogenic cells. This is a separate model from the human HEK N/O-glycosylation assays and does not establish clinical cartilage rescue. exposure: Decorin-transfected ATDC5 cells: 1 micromolar MnCl2, 1 millimolar galactose or 1 millimolar xylose for 36 hours. cross_nutrient: Manganese(II) ion (supplied_ion); Mouse TMEM165 (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 5; decorin migration", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 25939, "end_char": 27086, "text_sha256": "d94138936b018635104317fedba6c1298f0d54c6cd7b3f578b60000cea925bf5", "text_characters": 1147} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
Complete structured claim and evidence
D-galactose improved LAMP2 N-glycosylation only partially across the tested concentrations and times; the authors attributed residual underglycosylated protein to slow turnover.
D-Galactose → LAMP2 N-linked glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein); UDP-galactose (related_donor)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 subset recovery", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092}
experimental_model
Control and TMEM165-knockout HEK293 glycosylation assays
exposure
Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours.
limitations
Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Providing the sugar helped this readout, but some abnormal forms persisted throughout the tested conditions.
primary_references
[mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
tissue_or_cell_type
HEK293 cells and secretory glycoproteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 796–808
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft
### mn-gly-gal-n-linked-rescue D-galactose improved LAMP2 N-glycosylation only partially across the tested concentrations and times; the authors attributed residual underglycosylated protein to slow turnover. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the sugar helped this readout, but some abnormal forms persisted throughout the tested conditions. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 1: 1 micromolar MnCl2 for 8, 16 or 24 hours; galactose dose/time comparisons include 1 and 2.5 millimolar and 24–72 hours. cross_nutrient: Lysosome-associated membrane glycoprotein 2 (measured_protein); TMEM165 Golgi cation-homeostasis protein (affected_protein); UDP-galactose (related_donor) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 1; LAMP2 subset recovery", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 15482, "end_char": 17574, "text_sha256": "b7ffb42fc1d2094bd301171da36864a49f430e69b184ef0594b392c6ac7802dd", "text_characters": 2092} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
Complete structured claim and evidence
D-galactose partially improved the 24-hour O-glycan lectin readout but failed to rescue the three-day benzyl-GalNAc mass-spectrometry phenotype in TMEM165-knockout HEK cells.
D-Galactose → Mucin-type O-linked glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (effective_comparator)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; O-linked lectin and mass-spectrometry endpoints", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 19358, "end_char": 22255, "text_sha256": "e0b72a5427217107308f73e2304f47c761a25448096f516ca75c497eb8e389d5", "text_characters": 2897}
experimental_model
Control and TMEM165-knockout HEK293 glycosylation assays
exposure
Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days.
limitations
Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
One O-glycan test improved partly while a different test remained abnormal; galactose did not normalize this pathway.
primary_references
[mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
tissue_or_cell_type
HEK293 cells and secretory glycoproteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 810–822
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Control and TMEM165-knockout HEK293 glycosylation assays · source_derived_draft · unverified_draft
### mn-gly-gal-o-linked-limited D-galactose partially improved the 24-hour O-glycan lectin readout but failed to rescue the three-day benzyl-GalNAc mass-spectrometry phenotype in TMEM165-knockout HEK cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: One O-glycan test improved partly while a different test remained abnormal; galactose did not normalize this pathway. organism: Homo sapiens tissue_or_cell_type: HEK293 cells and secretory glycoproteins experimental_model: Control and TMEM165-knockout HEK293 glycosylation assays limitations: Cell rescue is not evidence for a safe human dose. N-linked, mucin-type O-linked and proteoglycan GAG endpoints are distinct; restoring one is not proof of global correction. exposure: Figure 3 lectin staining: 2.5 micromolar MnCl2 and/or 1 millimolar galactose for 24 hours. Figure 4: same additions with 250 micromolar benzyl-GalNAc for three days. cross_nutrient: TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (effective_comparator) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results; O-linked lectin and mass-spectrometry endpoints", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 19358, "end_char": 22255, "text_sha256": "e0b72a5427217107308f73e2304f47c761a25448096f516ca75c497eb8e389d5", "text_characters": 2897} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
Complete structured claim and evidence
D-galactose did not rescue the decorin glycosaminoglycan defect in the tested mouse Tmem165-knockout ATDC5 cells.
D-Galactose → Decorin glycosaminoglycan modification source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse TMEM165 (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 5; decorin", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 25939, "end_char": 27086, "text_sha256": "d94138936b018635104317fedba6c1298f0d54c6cd7b3f578b60000cea925bf5", "text_characters": 1147}
experimental_model
Tmem165-knockout mouse ATDC5 chondrogenic cells
exposure
Decorin-transfected ATDC5 cells: 1 micromolar MnCl2, 1 millimolar galactose or 1 millimolar xylose for 36 hours.
limitations
Decorin chondroitin-sulfate elongation in mouse chondrogenic cells. This is a separate model from the human HEK N/O-glycosylation assays and does not establish clinical cartilage rescue.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Improved N-glycosylation did not mean the proteoglycan defect was corrected.
primary_references
[mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
tissue_or_cell_type
Mouse chondrogenic ATDC5 cells and secreted decorin
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 824–836
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tmem165-knockout mouse ATDC5 chondrogenic cells · source_derived_draft · unverified_draft
### mn-gly-gal-gag-null D-galactose did not rescue the decorin glycosaminoglycan defect in the tested mouse Tmem165-knockout ATDC5 cells. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improved N-glycosylation did not mean the proteoglycan defect was corrected. organism: Mus musculus tissue_or_cell_type: Mouse chondrogenic ATDC5 cells and secreted decorin experimental_model: Tmem165-knockout mouse ATDC5 chondrogenic cells limitations: Decorin chondroitin-sulfate elongation in mouse chondrogenic cells. This is a separate model from the human HEK N/O-glycosylation assays and does not establish clinical cartilage rescue. exposure: Decorin-transfected ATDC5 cells: 1 micromolar MnCl2, 1 millimolar galactose or 1 millimolar xylose for 36 hours. cross_nutrient: Mouse TMEM165 (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/morelle2022.txt", "locator": "Results and Figure 5; decorin", "file_sha256": "91d05677c6d7bb4224f71742888e39533e3f130d59e6b2ffcae3e2b2c058e9aa", "start_char": 25939, "end_char": 27086, "text_sha256": "d94138936b018635104317fedba6c1298f0d54c6cd7b3f578b60000cea925bf5", "text_characters": 1147} [mn-gly-morelle2022] Differential Effects of D-Galactose Supplementation on Golgi Glycosylation Defects in TMEM165 Deficiency. (2022). https://pubmed.ncbi.nlm.nih.gov/35693943/ DOI: 10.3389/fcell.2022.903953
Complete structured claim and evidence
Serum-lot composition changed the severity and manganese responsiveness of TMEM165-knockout glycosylation defects; manganese concentration alone did not explain all differences.
Cell glycosylation response to serum-lot composition → LAMP2 N-linked glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (medium_component)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results; serum comparisons, ion measurements and manganese rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 6062, "end_char": 7726, "text_sha256": "9456189117cfb9840785f8afffbb38c52f855aaccc9c03b6fc1d4719550600d4", "text_characters": 1664}
experimental_model
TMEM165-knockout HEK cell cultures with different fetal bovine serum lots
exposure
Different serum lots; manganese, iron and galactose additions at the stated cellular concentrations.
limitations
Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The same genetic defect behaved differently as the surrounding nutrient mixture changed.
primary_references
[mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161
tissue_or_cell_type
Golgi glycosylation in HEK cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 838–850
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-knockout HEK cell cultures with different fetal bovine serum lots · source_derived_draft · unverified_draft
### mn-gly-serum-lot-context Serum-lot composition changed the severity and manganese responsiveness of TMEM165-knockout glycosylation defects; manganese concentration alone did not explain all differences. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same genetic defect behaved differently as the surrounding nutrient mixture changed. organism: Homo sapiens tissue_or_cell_type: Golgi glycosylation in HEK cells experimental_model: TMEM165-knockout HEK cell cultures with different fetal bovine serum lots limitations: Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens. exposure: Different serum lots; manganese, iron and galactose additions at the stated cellular concentrations. cross_nutrient: TMEM165 Golgi cation-homeostasis protein (affected_protein); Manganese(II) ion (medium_component) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results; serum comparisons, ion measurements and manganese rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 6062, "end_char": 7726, "text_sha256": "9456189117cfb9840785f8afffbb38c52f855aaccc9c03b6fc1d4719550600d4", "text_characters": 1664} [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161
Complete structured claim and evidence
At 5 micromolar, both Fe(III) and Fe(II) produced partially glycosylated LAMP2 forms; manganese was more effective in the compared culture conditions.
Ferric iron → LAMP2 N-linked glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Ferrous iron (tested_ion); Manganese(II) ion (comparison_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 8; comparative ion rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 8502, "end_char": 9711, "text_sha256": "beb10a451c339fb08a468255ff298f79c3617f1b83b0c2f4a31a4470d2e46aa6", "text_characters": 1209}
experimental_model
TMEM165-knockout HEK cell cultures with different fetal bovine serum lots
exposure
Fe(II), Fe(III) or Mn(II), each at 5 micromolar for 16 hours in the Figure 8 comparison.
limitations
Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Iron changed this cellular readout but did not act as an equivalent manganese replacement.
primary_references
[mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161
tissue_or_cell_type
Golgi glycosylation in HEK cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 852–864
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-knockout HEK cell cultures with different fetal bovine serum lots · source_derived_draft · unverified_draft
### mn-gly-iron-glycan-partial At 5 micromolar, both Fe(III) and Fe(II) produced partially glycosylated LAMP2 forms; manganese was more effective in the compared culture conditions. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron changed this cellular readout but did not act as an equivalent manganese replacement. organism: Homo sapiens tissue_or_cell_type: Golgi glycosylation in HEK cells experimental_model: TMEM165-knockout HEK cell cultures with different fetal bovine serum lots limitations: Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens. exposure: Fe(II), Fe(III) or Mn(II), each at 5 micromolar for 16 hours in the Figure 8 comparison. cross_nutrient: Ferrous iron (tested_ion); Manganese(II) ion (comparison_ion); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 8; comparative ion rescue", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 8502, "end_char": 9711, "text_sha256": "beb10a451c339fb08a468255ff298f79c3617f1b83b0c2f4a31a4470d2e46aa6", "text_characters": 1209} [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161
Complete structured claim and evidence
With serum lot 4, combining 1 micromolar manganese and 1 millimolar galactose restored fully glycosylated LAMP2 more effectively than either alone.
Galactose and manganese coadministration → LAMP2 N-linked glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Manganese(II) ion (combined_ion); D-Galactose (combined_sugar); TMEM165 Golgi cation-homeostasis protein (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 9; use 1 mM galactose from setup and legend, rather than the subsequent prose unit typo", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 9804, "end_char": 10848, "text_sha256": "3547ececbb7198f699bd64bcd033276f18a8e3d3b7c02c4f907f25a267444bec", "text_characters": 1044}
experimental_model
TMEM165-knockout HEK cell cultures with different fetal bovine serum lots
exposure
Serum lot 4; 1 micromolar manganese, 1 millimolar galactose or both for 24 hours.
limitations
Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
A combined supply improved a result that responded poorly to either component alone.
primary_references
[mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161
tissue_or_cell_type
Golgi glycosylation in HEK cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 866–878
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · TMEM165-knockout HEK cell cultures with different fetal bovine serum lots · source_derived_draft · unverified_draft
### mn-gly-gal-mn-combination With serum lot 4, combining 1 micromolar manganese and 1 millimolar galactose restored fully glycosylated LAMP2 more effectively than either alone. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A combined supply improved a result that responded poorly to either component alone. organism: Homo sapiens tissue_or_cell_type: Golgi glycosylation in HEK cells experimental_model: TMEM165-knockout HEK cell cultures with different fetal bovine serum lots limitations: Serum manganese contributes to the result but is not the sole determinant. These are medium concentrations, not blood thresholds or supplementation regimens. exposure: Serum lot 4; 1 micromolar manganese, 1 millimolar galactose or both for 24 hours. cross_nutrient: Manganese(II) ion (combined_ion); D-Galactose (combined_sugar); TMEM165 Golgi cation-homeostasis protein (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/serum2020.txt", "locator": "Results and Figure 9; use 1 mM galactose from setup and legend, rather than the subsequent prose unit typo", "file_sha256": "203365df4c837f50483da9ec16cb0882674cf4903bbda21aa7374205d72ade69", "start_char": 9804, "end_char": 10848, "text_sha256": "3547ececbb7198f699bd64bcd033276f18a8e3d3b7c02c4f907f25a267444bec", "text_characters": 1044} [mn-gly-serum2020] Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. (2020). https://pubmed.ncbi.nlm.nih.gov/31415112/ DOI: 10.1002/jimd.12161
Complete structured claim and evidence
Mammary epithelial Tmem165 deletion reduced lactose biosynthesis in lactating mice.
Mouse mammary epithelial TMEM165 loss → Mammary lactose biosynthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse TMEM165 (affected_protein); Lactose (affected_product)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/milk2019.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "start_char": 0, "end_char": 1462, "text_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "text_characters": 1462}
experimental_model
Conditional mammary epithelial Tmem165 deletion in mice
exposure
Tissue-specific deletion with milk composition and pup-growth measurements.
limitations
The primary abstract supports normalized milk minerals and reduced lactose; altered concentration can reflect less milk dilution. Proposed cation/H+ exchange is an interpretation, not a transport stoichiometry measured here.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
Manganese-handling machinery in the milk-producing cell affected milk production.
primary_references
[mn-gly-milk2019] Milk biosynthesis requires the Golgi cation exchanger TMEM165. (2019). https://pubmed.ncbi.nlm.nih.gov/30622138/ DOI: 10.1074/jbc.ra118.006270
tissue_or_cell_type
Lactating mammary gland and milk
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 880–892
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional mammary epithelial Tmem165 deletion in mice · source_derived_draft · unverified_draft
### mn-gly-mammary-lactose Mammary epithelial Tmem165 deletion reduced lactose biosynthesis in lactating mice. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese-handling machinery in the milk-producing cell affected milk production. organism: Mus musculus tissue_or_cell_type: Lactating mammary gland and milk experimental_model: Conditional mammary epithelial Tmem165 deletion in mice limitations: The primary abstract supports normalized milk minerals and reduced lactose; altered concentration can reflect less milk dilution. Proposed cation/H+ exchange is an interpretation, not a transport stoichiometry measured here. exposure: Tissue-specific deletion with milk composition and pup-growth measurements. cross_nutrient: Mouse TMEM165 (affected_protein); Lactose (affected_product) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/milk2019.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "start_char": 0, "end_char": 1462, "text_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "text_characters": 1462} [mn-gly-milk2019] Milk biosynthesis requires the Golgi cation exchanger TMEM165. (2019). https://pubmed.ncbi.nlm.nih.gov/30622138/ DOI: 10.1074/jbc.ra118.006270
Complete structured claim and evidence
After normalization to milk protein, calcium and manganese were lower in milk from Tmem165-deficient dams.
Mouse mammary epithelial TMEM165 loss → Milk manganese normalized to protein source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse TMEM165 (affected_protein); Milk calcium normalized to protein (measured_endpoint); Calcium (affected_nutrient); Manganese (affected_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/milk2019.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "start_char": 0, "end_char": 1462, "text_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "text_characters": 1462}
experimental_model
Conditional mammary epithelial Tmem165 deletion in mice
exposure
Tissue-specific deletion with milk composition and pup-growth measurements.
limitations
The primary abstract supports normalized milk minerals and reduced lactose; altered concentration can reflect less milk dilution. Proposed cation/H+ exchange is an interpretation, not a transport stoichiometry measured here.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
The defect changed milk manganese and calcium relative to its protein content.
primary_references
[mn-gly-milk2019] Milk biosynthesis requires the Golgi cation exchanger TMEM165. (2019). https://pubmed.ncbi.nlm.nih.gov/30622138/ DOI: 10.1074/jbc.ra118.006270
tissue_or_cell_type
Lactating mammary gland and milk
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 894–906
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional mammary epithelial Tmem165 deletion in mice · source_derived_draft · unverified_draft
### mn-gly-mammary-minerals After normalization to milk protein, calcium and manganese were lower in milk from Tmem165-deficient dams. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect changed milk manganese and calcium relative to its protein content. organism: Mus musculus tissue_or_cell_type: Lactating mammary gland and milk experimental_model: Conditional mammary epithelial Tmem165 deletion in mice limitations: The primary abstract supports normalized milk minerals and reduced lactose; altered concentration can reflect less milk dilution. Proposed cation/H+ exchange is an interpretation, not a transport stoichiometry measured here. exposure: Tissue-specific deletion with milk composition and pup-growth measurements. cross_nutrient: Mouse TMEM165 (affected_protein); Milk calcium normalized to protein (measured_endpoint); Calcium (affected_nutrient); Manganese (affected_nutrient) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/milk2019.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "start_char": 0, "end_char": 1462, "text_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "text_characters": 1462} [mn-gly-milk2019] Milk biosynthesis requires the Golgi cation exchanger TMEM165. (2019). https://pubmed.ncbi.nlm.nih.gov/30622138/ DOI: 10.1074/jbc.ra118.006270
Complete structured claim and evidence
The COLGALT1 GT2 catalytic site contains a Glu-Asp-Asp motif important for manganese binding.
Mn2+ → COLGALT1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
UDP-galactose (donor_substrate)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/colgalt2025.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "start_char": 0, "end_char": 1331, "text_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "text_characters": 1331}
experimental_model
Human COLGALT1 structural and biochemical assays
exposure
Metal substitution and structural-domain comparisons.
limitations
Modification of collagen-bound hydroxylysine does not establish that extra dietary manganese or free lysine improves collagen in a person.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The collagen sugar-transfer reaction has a defined manganese-binding site.
primary_references
[mn-gly-colgalt2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1. (2025). https://pubmed.ncbi.nlm.nih.gov/40240392/ DOI: 10.1038/s41467-025-59017-5
tissue_or_cell_type
Purified protein and collagen peptides
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 908–920
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human COLGALT1 structural and biochemical assays · source_derived_draft · unverified_draft
### mn-gly-colgalt-gt2-metal The COLGALT1 GT2 catalytic site contains a Glu-Asp-Asp motif important for manganese binding. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The collagen sugar-transfer reaction has a defined manganese-binding site. organism: Homo sapiens tissue_or_cell_type: Purified protein and collagen peptides experimental_model: Human COLGALT1 structural and biochemical assays limitations: Modification of collagen-bound hydroxylysine does not establish that extra dietary manganese or free lysine improves collagen in a person. exposure: Metal substitution and structural-domain comparisons. cross_nutrient: UDP-galactose (donor_substrate) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/colgalt2025.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "start_char": 0, "end_char": 1331, "text_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "text_characters": 1331} [mn-gly-colgalt2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1. (2025). https://pubmed.ncbi.nlm.nih.gov/40240392/ DOI: 10.1038/s41467-025-59017-5
Complete structured claim and evidence
Calcium and UDP-galactose bound in COLGALT1’s noncatalytic GT1 domain contribute to folding stability.
Calcium ion → COLGALT1 folding stability source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
COLGALT1 (affected_protein); UDP-galactose (stabilizing_ligand); Manganese(II) ion (distinct_catalytic_ion)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/colgalt2025.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "start_char": 0, "end_char": 1331, "text_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "text_characters": 1331}
experimental_model
Human COLGALT1 structural and biochemical assays
exposure
Metal substitution and structural-domain comparisons.
limitations
Modification of collagen-bound hydroxylysine does not establish that extra dietary manganese or free lysine improves collagen in a person.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Calcium and the donor sugar also help stabilize a separate part of this manganese enzyme.
primary_references
[mn-gly-colgalt2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1. (2025). https://pubmed.ncbi.nlm.nih.gov/40240392/ DOI: 10.1038/s41467-025-59017-5
tissue_or_cell_type
Purified protein and collagen peptides
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 922–934
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human COLGALT1 structural and biochemical assays · source_derived_draft · unverified_draft
### mn-gly-colgalt-gt1-stability Calcium and UDP-galactose bound in COLGALT1’s noncatalytic GT1 domain contribute to folding stability. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium and the donor sugar also help stabilize a separate part of this manganese enzyme. organism: Homo sapiens tissue_or_cell_type: Purified protein and collagen peptides experimental_model: Human COLGALT1 structural and biochemical assays limitations: Modification of collagen-bound hydroxylysine does not establish that extra dietary manganese or free lysine improves collagen in a person. exposure: Metal substitution and structural-domain comparisons. cross_nutrient: COLGALT1 (affected_protein); UDP-galactose (stabilizing_ligand); Manganese(II) ion (distinct_catalytic_ion) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/colgalt2025.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "start_char": 0, "end_char": 1331, "text_sha256": "5a42e5928c56f4e312768d79c9a5601b6f9e76a44bcdd9ede4bc8ea0c8985b60", "text_characters": 1331} [mn-gly-colgalt2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1. (2025). https://pubmed.ncbi.nlm.nih.gov/40240392/ DOI: 10.1038/s41467-025-59017-5
Complete structured claim and evidence
Pups nursed by mammary Tmem165-deficient dams had impaired growth.
Mouse mammary epithelial TMEM165 loss → Growth of nursing mouse pups source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Mouse TMEM165 (affected_protein); Lactose (affected_product)
evidence_span
{"source_cache": "artifacts/manganese-glycosylation-sources/milk2019.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "start_char": 0, "end_char": 1462, "text_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "text_characters": 1462}
experimental_model
Conditional mammary epithelial Tmem165 deletion in mice
exposure
Tissue-specific deletion with milk composition and pup-growth measurements.
limitations
The primary abstract supports normalized milk minerals and reduced lactose; altered concentration can reflect less milk dilution. Proposed cation/H+ exchange is an interpretation, not a transport stoichiometry measured here.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Mus musculus
plain_language
The milk-producing-cell defect was accompanied by slower growth in nursing pups.
primary_references
[mn-gly-milk2019] Milk biosynthesis requires the Golgi cation exchanger TMEM165. (2019). https://pubmed.ncbi.nlm.nih.gov/30622138/ DOI: 10.1074/jbc.ra118.006270
tissue_or_cell_type
Lactating mammary gland and milk
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 936–948
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional mammary epithelial Tmem165 deletion in mice · source_derived_draft · unverified_draft
### mn-gly-mammary-pup-growth Pups nursed by mammary Tmem165-deficient dams had impaired growth. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The milk-producing-cell defect was accompanied by slower growth in nursing pups. organism: Mus musculus tissue_or_cell_type: Lactating mammary gland and milk experimental_model: Conditional mammary epithelial Tmem165 deletion in mice limitations: The primary abstract supports normalized milk minerals and reduced lactose; altered concentration can reflect less milk dilution. Proposed cation/H+ exchange is an interpretation, not a transport stoichiometry measured here. exposure: Tissue-specific deletion with milk composition and pup-growth measurements. cross_nutrient: Mouse TMEM165 (affected_protein); Lactose (affected_product) evidence_span: {"source_cache": "artifacts/manganese-glycosylation-sources/milk2019.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "start_char": 0, "end_char": 1462, "text_sha256": "88bcb50ecdb918803c5950bcff8f48665dbd17148b365a4f9f3b463fe7edd2a4", "text_characters": 1462} [mn-gly-milk2019] Milk biosynthesis requires the Golgi cation exchanger TMEM165. (2019). https://pubmed.ncbi.nlm.nih.gov/30622138/ DOI: 10.1074/jbc.ra118.006270
Complete structured claim and evidence
Five of seven men developed miliaria crystallina during the depletion experiment; it disappeared as repletion began.
Controlled manganese-depletion diet → Miliaria crystallina skin eruption source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Manganese handling and the measured downstream function.
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/friedman1987.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "start_char": 0, "end_char": 1186, "text_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "text_characters": 1186}
experimental_model
Controlled depletion and repletion in seven men aged 19–22
exposure
Three weeks at 2.59 mg Mn/day, then 39 days at 0.11 mg/day; repletion at 1.53 and 2.55 mg/day for five days each.
limitations
Small sequential purified-diet study without a parallel control. Findings are not diagnostic criteria; the paper’s factorial requirement estimates are not current recommended intakes.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Severe restriction was accompanied by a reversible skin eruption in this small study.
primary_references
[mn-clin-friedman1987] Manganese balance and clinical observations in young men fed a manganese-deficient diet. (1987). https://pubmed.ncbi.nlm.nih.gov/3819860/ DOI: 10.1093/jn/117.1.133
tissue_or_cell_type
Skin and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 950–962
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled depletion and repletion in seven men aged 19–22 · source_derived_draft · unverified_draft
### mn-clin-depletion-skin Five of seven men developed miliaria crystallina during the depletion experiment; it disappeared as repletion began. Condition category: nutrient_deficiency nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe restriction was accompanied by a reversible skin eruption in this small study. organism: Homo sapiens tissue_or_cell_type: Skin and plasma experimental_model: Controlled depletion and repletion in seven men aged 19–22 limitations: Small sequential purified-diet study without a parallel control. Findings are not diagnostic criteria; the paper’s factorial requirement estimates are not current recommended intakes. exposure: Three weeks at 2.59 mg Mn/day, then 39 days at 0.11 mg/day; repletion at 1.53 and 2.55 mg/day for five days each. cross_nutrient: Manganese handling and the measured downstream function. evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/friedman1987.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "start_char": 0, "end_char": 1186, "text_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "text_characters": 1186} [mn-clin-friedman1987] Manganese balance and clinical observations in young men fed a manganese-deficient diet. (1987). https://pubmed.ncbi.nlm.nih.gov/3819860/ DOI: 10.1093/jn/117.1.133
Complete structured claim and evidence
Plasma cholesterol fell during baseline as well as depletion and did not respond during the ten-day manganese repletion period.
Controlled manganese-depletion diet → Plasma cholesterol concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Manganese handling and the measured downstream function.
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/friedman1987.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "start_char": 0, "end_char": 1186, "text_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "text_characters": 1186}
experimental_model
Controlled depletion and repletion in seven men aged 19–22
exposure
Three weeks at 2.59 mg Mn/day, then 39 days at 0.11 mg/day; repletion at 1.53 and 2.55 mg/day for five days each.
limitations
Small sequential purified-diet study without a parallel control. Findings are not diagnostic criteria; the paper’s factorial requirement estimates are not current recommended intakes.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The cholesterol change was not a clean manganese-specific response.
primary_references
[mn-clin-friedman1987] Manganese balance and clinical observations in young men fed a manganese-deficient diet. (1987). https://pubmed.ncbi.nlm.nih.gov/3819860/ DOI: 10.1093/jn/117.1.133
tissue_or_cell_type
Skin and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 964–976
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled depletion and repletion in seven men aged 19–22 · source_derived_draft · unverified_draft
### mn-clin-depletion-cholesterol Plasma cholesterol fell during baseline as well as depletion and did not respond during the ten-day manganese repletion period. Condition category: nutrient_deficiency nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cholesterol change was not a clean manganese-specific response. organism: Homo sapiens tissue_or_cell_type: Skin and plasma experimental_model: Controlled depletion and repletion in seven men aged 19–22 limitations: Small sequential purified-diet study without a parallel control. Findings are not diagnostic criteria; the paper’s factorial requirement estimates are not current recommended intakes. exposure: Three weeks at 2.59 mg Mn/day, then 39 days at 0.11 mg/day; repletion at 1.53 and 2.55 mg/day for five days each. cross_nutrient: Manganese handling and the measured downstream function. evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/friedman1987.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "start_char": 0, "end_char": 1186, "text_sha256": "ddc0b39d872786b905ca06d9b2470ebdf926ef42822e346f6bf003a180be4ba6", "text_characters": 1186} [mn-clin-friedman1987] Manganese balance and clinical observations in young men fed a manganese-deficient diet. (1987). https://pubmed.ncbi.nlm.nih.gov/3819860/ DOI: 10.1093/jn/117.1.133
Complete structured claim and evidence
Manganese absorption was greatest in the low-ferritin group on the low-manganese diet and lowest in the high-ferritin group.
Serum ferritin concentration → Intestinal manganese absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Iron (interacting_nutrient); Manganese (absorbed_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731}
experimental_model
Crossover isotope study in 26 healthy young women
exposure
Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each.
limitations
Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The amount of manganese absorbed depended partly on iron stores.
primary_references
[mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37
tissue_or_cell_type
Gut, whole-body tracer retention and blood
trigger_kind
biomarker_context Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 978–990
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope study in 26 healthy young women · source_derived_draft · unverified_draft
### mn-clin-iron-stores-absorption Manganese absorption was greatest in the low-ferritin group on the low-manganese diet and lowest in the high-ferritin group. Condition category: biomarker_context nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The amount of manganese absorbed depended partly on iron stores. organism: Homo sapiens tissue_or_cell_type: Gut, whole-body tracer retention and blood experimental_model: Crossover isotope study in 26 healthy young women limitations: Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause. exposure: Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each. cross_nutrient: Iron (interacting_nutrient); Manganese (absorbed_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731} [mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37
Complete structured claim and evidence
Tracer half-life was longest with high ferritin and low manganese intake, and shortest during the high-manganese diets.
Serum ferritin concentration → Manganese tracer biological half-life source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Iron (interacting_nutrient); Manganese (retained_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731}
experimental_model
Crossover isotope study in 26 healthy young women
exposure
Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each.
limitations
Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Absorbing manganese and keeping it are separately regulated.
primary_references
[mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37
tissue_or_cell_type
Gut, whole-body tracer retention and blood
trigger_kind
biomarker_context Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 992–1004
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope study in 26 healthy young women · source_derived_draft · unverified_draft
### mn-clin-iron-stores-retention Tracer half-life was longest with high ferritin and low manganese intake, and shortest during the high-manganese diets. Condition category: biomarker_context nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorbing manganese and keeping it are separately regulated. organism: Homo sapiens tissue_or_cell_type: Gut, whole-body tracer retention and blood experimental_model: Crossover isotope study in 26 healthy young women limitations: Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause. exposure: Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each. cross_nutrient: Iron (interacting_nutrient); Manganese (retained_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731} [mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37
Complete structured claim and evidence
The high-ferritin group had lower measured arginase activity in the controlled dietary comparison.
Serum ferritin concentration → Measured arginase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Iron (associated_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731}
experimental_model
Crossover isotope study in 26 healthy young women
exposure
Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each.
limitations
Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
An enzyme readout also varied with iron stores.
primary_references
[mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37
tissue_or_cell_type
Gut, whole-body tracer retention and blood
trigger_kind
biomarker_context Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1006–1018
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover isotope study in 26 healthy young women · source_derived_draft · unverified_draft
### mn-clin-iron-stores-arginase The high-ferritin group had lower measured arginase activity in the controlled dietary comparison. Condition category: biomarker_context nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme readout also varied with iron stores. organism: Homo sapiens tissue_or_cell_type: Gut, whole-body tracer retention and blood experimental_model: Crossover isotope study in 26 healthy young women limitations: Ferritin defines the comparison groups, not cellular manganese deficiency. Retention and absorption are separate measurements; the study does not identify a specific transporter as their cause. exposure: Eleven women with serum ferritin >50 micrograms/L and 15 with <15 micrograms/L; diets at 0.7 or 9.5 mg Mn/day for 60 days each. cross_nutrient: Iron (associated_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1999.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "start_char": 0, "end_char": 1731, "text_sha256": "3ec791f205459093fec1dfac522bbb6241aa1199894886be9c64d4c2eb2b97d7", "text_characters": 1731} [mn-clin-finley1999] Manganese absorption and retention by young women is associated with serum ferritin concentration. (1999). https://pubmed.ncbi.nlm.nih.gov/10393136/ DOI: 10.1093/ajcn/70.1.37
Complete structured claim and evidence
Adding calcium to the human-milk test meal reduced manganese absorption in adults.
Calcium → Intestinal manganese absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese (absorbed_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912}
experimental_model
Paired radiotracer test-meal study in adults
exposure
Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions.
limitations
These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Calcium changed manganese uptake in this particular meal.
primary_references
[mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
tissue_or_cell_type
Intestinal absorption
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1020–1032
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radiotracer test-meal study in adults · source_derived_draft · unverified_draft
### mn-clin-meal-calcium Adding calcium to the human-milk test meal reduced manganese absorption in adults. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium changed manganese uptake in this particular meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Paired radiotracer test-meal study in adults limitations: These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows. exposure: Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions. cross_nutrient: Manganese (absorbed_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912} [mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
Complete structured claim and evidence
Iron added to the wheat-bread test meal did not significantly change manganese absorption.
Iron → Intestinal manganese absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese (measured_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912}
experimental_model
Paired radiotracer test-meal study in adults
exposure
Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions.
limitations
These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
An iron interaction was not detected in every meal.
primary_references
[mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
tissue_or_cell_type
Intestinal absorption
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1034–1046
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radiotracer test-meal study in adults · source_derived_draft · unverified_draft
### mn-clin-meal-iron Iron added to the wheat-bread test meal did not significantly change manganese absorption. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An iron interaction was not detected in every meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Paired radiotracer test-meal study in adults limitations: These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows. exposure: Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions. cross_nutrient: Manganese (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912} [mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
Complete structured claim and evidence
Magnesium added to the wheat-bread test meal did not significantly change manganese absorption.
Magnesium → Intestinal manganese absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese (measured_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912}
experimental_model
Paired radiotracer test-meal study in adults
exposure
Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions.
limitations
These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Magnesium did not inhibit manganese uptake in this bread experiment.
primary_references
[mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
tissue_or_cell_type
Intestinal absorption
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1048–1060
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radiotracer test-meal study in adults · source_derived_draft · unverified_draft
### mn-clin-meal-magnesium Magnesium added to the wheat-bread test meal did not significantly change manganese absorption. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium did not inhibit manganese uptake in this bread experiment. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Paired radiotracer test-meal study in adults limitations: These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows. exposure: Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions. cross_nutrient: Manganese (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912} [mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
Complete structured claim and evidence
Adding phytate, phosphate or ascorbic acid to the formula test meals did not significantly alter manganese absorption in adults.
Intestinal manganese absorption → Phytic acid / phytate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Inorganic phosphate (Pi; protonation depends on pH) (tested_addition); L-Ascorbate (tested_addition); Manganese (measured_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912}
experimental_model
Paired radiotracer test-meal study in adults
exposure
Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions.
limitations
These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The tested additions had no detectable effect in this formula matrix.
primary_references
[mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
tissue_or_cell_type
Intestinal absorption
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1062–1074
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radiotracer test-meal study in adults · source_derived_draft · unverified_draft
### mn-clin-meal-formula-additions Adding phytate, phosphate or ascorbic acid to the formula test meals did not significantly alter manganese absorption in adults. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested additions had no detectable effect in this formula matrix. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Paired radiotracer test-meal study in adults limitations: These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows. exposure: Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions. cross_nutrient: Inorganic phosphate (Pi; protonation depends on pH) (tested_addition); L-Ascorbate (tested_addition); Manganese (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912} [mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065
Complete structured claim and evidence
Men absorbed less manganese tracer than women but retained the absorbed tracer for longer.
Intestinal manganese absorption → Whole-body manganese retention source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Plasma ferritin concentration (associated_biomarker); Iron (possible_context)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/finley1994.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "start_char": 0, "end_char": 1009, "text_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "text_characters": 1009}
experimental_model
Whole-body manganese tracer study in 20 men and 20 women
exposure
Adequate-manganese diet and oral tracer meal; counting continued for 70 days.
limitations
Sex-associated findings may reflect iron status and other differences. Reported tracer-activity units in the abstract were not independently verified and are not used here.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Lower absorption did not mean faster loss afterward.
primary_references
[mn-clin-finley1994] Sex affects manganese absorption and retention by humans from a diet adequate in manganese. (1994). https://pubmed.ncbi.nlm.nih.gov/7985639/ DOI: 10.1093/ajcn/60.6.949
tissue_or_cell_type
Intestinal absorption and whole-body retention
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1076–1088
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body manganese tracer study in 20 men and 20 women · source_derived_draft · unverified_draft
### mn-clin-sex-absorption-retention Men absorbed less manganese tracer than women but retained the absorbed tracer for longer. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lower absorption did not mean faster loss afterward. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption and whole-body retention experimental_model: Whole-body manganese tracer study in 20 men and 20 women limitations: Sex-associated findings may reflect iron status and other differences. Reported tracer-activity units in the abstract were not independently verified and are not used here. exposure: Adequate-manganese diet and oral tracer meal; counting continued for 70 days. cross_nutrient: Plasma ferritin concentration (associated_biomarker); Iron (possible_context) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1994.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "start_char": 0, "end_char": 1009, "text_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "text_characters": 1009} [mn-clin-finley1994] Sex affects manganese absorption and retention by humans from a diet adequate in manganese. (1994). https://pubmed.ncbi.nlm.nih.gov/7985639/ DOI: 10.1093/ajcn/60.6.949
Complete structured claim and evidence
Fitting days 10–20 gave higher absorption and shorter half-life estimates than fitting days 19–70 of the same retention curves.
Manganese tracer biological half-life → Whole-body manganese retention source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese handling and the measured downstream function.
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/finley1994.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "start_char": 0, "end_char": 1009, "text_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "text_characters": 1009}
experimental_model
Whole-body manganese tracer study in 20 men and 20 women
exposure
Adequate-manganese diet and oral tracer meal; counting continued for 70 days.
limitations
Sex-associated findings may reflect iron status and other differences. Reported tracer-activity units in the abstract were not independently verified and are not used here.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The observation window changed the calculated manganese estimates.
primary_references
[mn-clin-finley1994] Sex affects manganese absorption and retention by humans from a diet adequate in manganese. (1994). https://pubmed.ncbi.nlm.nih.gov/7985639/ DOI: 10.1093/ajcn/60.6.949
tissue_or_cell_type
Intestinal absorption and whole-body retention
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1090–1102
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-body manganese tracer study in 20 men and 20 women · source_derived_draft · unverified_draft
### mn-clin-tracer-window Fitting days 10–20 gave higher absorption and shorter half-life estimates than fitting days 19–70 of the same retention curves. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The observation window changed the calculated manganese estimates. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption and whole-body retention experimental_model: Whole-body manganese tracer study in 20 men and 20 women limitations: Sex-associated findings may reflect iron status and other differences. Reported tracer-activity units in the abstract were not independently verified and are not used here. exposure: Adequate-manganese diet and oral tracer meal; counting continued for 70 days. cross_nutrient: Manganese handling and the measured downstream function. evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/finley1994.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "start_char": 0, "end_char": 1009, "text_sha256": "f24059b0e56ddb384da59918af300da971697d38bdac6be5775a39d65f5209a0", "text_characters": 1009} [mn-clin-finley1994] Sex affects manganese absorption and retention by humans from a diet adequate in manganese. (1994). https://pubmed.ncbi.nlm.nih.gov/7985639/ DOI: 10.1093/ajcn/60.6.949
Complete structured claim and evidence
Manganese supplementation increased lymphocyte MnSOD activity from baseline.
Manganese → Lymphocyte manganese superoxide dismutase activity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mitochondrial superoxide dismutase / SOD2 (measured_enzyme); Iron (factorial_comparator)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956}
experimental_model
124-day supplementation study in 47 women
exposure
Placebo, 60 mg iron/day, 15 mg manganese/day or both.
limitations
Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The manganese enzyme responded in the sampled immune cells.
primary_references
[mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
tissue_or_cell_type
Lymphocytes, serum and urine
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1104–1116
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124-day supplementation study in 47 women · source_derived_draft · unverified_draft
### mn-clin-supplement-lymphocyte-sod Manganese supplementation increased lymphocyte MnSOD activity from baseline. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The manganese enzyme responded in the sampled immune cells. organism: Homo sapiens tissue_or_cell_type: Lymphocytes, serum and urine experimental_model: 124-day supplementation study in 47 women limitations: Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold. exposure: Placebo, 60 mg iron/day, 15 mg manganese/day or both. cross_nutrient: Mitochondrial superoxide dismutase / SOD2 (measured_enzyme); Iron (factorial_comparator) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956} [mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
Complete structured claim and evidence
Serum manganese increased from baseline during manganese supplementation.
Manganese → Serum manganese concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese handling and the measured downstream function.
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956}
experimental_model
124-day supplementation study in 47 women
exposure
Placebo, 60 mg iron/day, 15 mg manganese/day or both.
limitations
Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The circulating measurement responded to the experimental intake.
primary_references
[mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
tissue_or_cell_type
Lymphocytes, serum and urine
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1118–1130
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124-day supplementation study in 47 women · source_derived_draft · unverified_draft
### mn-clin-supplement-serum Serum manganese increased from baseline during manganese supplementation. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The circulating measurement responded to the experimental intake. organism: Homo sapiens tissue_or_cell_type: Lymphocytes, serum and urine experimental_model: 124-day supplementation study in 47 women limitations: Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold. exposure: Placebo, 60 mg iron/day, 15 mg manganese/day or both. cross_nutrient: Manganese handling and the measured downstream function. evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956} [mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
Complete structured claim and evidence
Manganese supplementation did not change measured urinary manganese excretion.
Manganese → Urinary manganese excretion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese handling and the measured downstream function.
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956}
experimental_model
124-day supplementation study in 47 women
exposure
Placebo, 60 mg iron/day, 15 mg manganese/day or both.
limitations
Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Urinary manganese did not track the serum response in this study.
primary_references
[mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
tissue_or_cell_type
Lymphocytes, serum and urine
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1132–1144
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124-day supplementation study in 47 women · source_derived_draft · unverified_draft
### mn-clin-supplement-urine Manganese supplementation did not change measured urinary manganese excretion. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Urinary manganese did not track the serum response in this study. organism: Homo sapiens tissue_or_cell_type: Lymphocytes, serum and urine experimental_model: 124-day supplementation study in 47 women limitations: Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold. exposure: Placebo, 60 mg iron/day, 15 mg manganese/day or both. cross_nutrient: Manganese handling and the measured downstream function. evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956} [mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
Complete structured claim and evidence
Manganese supplementation did not change any measured indices of iron status.
Manganese → Measured human iron-status indices source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Iron (measured_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956}
experimental_model
124-day supplementation study in 47 women
exposure
Placebo, 60 mg iron/day, 15 mg manganese/day or both.
limitations
Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
An interaction need not produce a detectable change in both minerals.
primary_references
[mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
tissue_or_cell_type
Lymphocytes, serum and urine
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1146–1158
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 124-day supplementation study in 47 women · source_derived_draft · unverified_draft
### mn-clin-supplement-iron-null Manganese supplementation did not change any measured indices of iron status. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: An interaction need not produce a detectable change in both minerals. organism: Homo sapiens tissue_or_cell_type: Lymphocytes, serum and urine experimental_model: 124-day supplementation study in 47 women limitations: Historical experimental doses, not intake advice. Abstract reports manganese changes from baseline; biomarkers do not demonstrate improved health or establish a deficiency threshold. exposure: Placebo, 60 mg iron/day, 15 mg manganese/day or both. cross_nutrient: Iron (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992a.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "start_char": 0, "end_char": 956, "text_sha256": "2fbf15cf32ba80f68c4f4efaa7fa50de76b90094438325cc6632b7d447e22227", "text_characters": 956} [mn-clin-davis1992a] Longitudinal changes of manganese-dependent superoxide dismutase and other indexes of manganese and iron status in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1550052/ DOI: 10.1093/ajcn/55.3.747
Complete structured claim and evidence
Higher nonheme-iron intake was associated with lower serum and urinary manganese and lymphocyte MnSOD activity; heme-iron intake showed no consistent manganese pattern.
Nonheme dietary iron → Lymphocyte manganese superoxide dismutase activity source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Heme iron (comparison_form); Serum manganese concentration (associated_endpoint); Urinary manganese excretion (associated_endpoint); Manganese (affected_nutrient); Iron (associated_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/davis1992b.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "start_char": 0, "end_char": 1172, "text_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "text_characters": 1172}
experimental_model
Dietary association analysis in 47 women consuming usual diets
exposure
Comparisons of manganese, heme-iron and nonheme-iron intake.
limitations
Observational food-pattern associations cannot isolate a transporter or iron itself from correlated dietary factors. This may analyze participants related to the companion supplementation report; papers are not independent trials.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Food form and the rest of the diet changed the observed iron–manganese relationship.
primary_references
[mn-clin-davis1992b] Interactions among dietary manganese, heme iron, and nonheme iron in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1415012/ DOI: 10.1093/ajcn/56.5.926
tissue_or_cell_type
Serum, urine and lymphocyte enzymes
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1160–1172
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary association analysis in 47 women consuming usual diets · source_derived_draft · unverified_draft
### mn-clin-nonheme-association Higher nonheme-iron intake was associated with lower serum and urinary manganese and lymphocyte MnSOD activity; heme-iron intake showed no consistent manganese pattern. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Food form and the rest of the diet changed the observed iron–manganese relationship. organism: Homo sapiens tissue_or_cell_type: Serum, urine and lymphocyte enzymes experimental_model: Dietary association analysis in 47 women consuming usual diets limitations: Observational food-pattern associations cannot isolate a transporter or iron itself from correlated dietary factors. This may analyze participants related to the companion supplementation report; papers are not independent trials. exposure: Comparisons of manganese, heme-iron and nonheme-iron intake. cross_nutrient: Heme iron (comparison_form); Serum manganese concentration (associated_endpoint); Urinary manganese excretion (associated_endpoint); Manganese (affected_nutrient); Iron (associated_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davis1992b.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "start_char": 0, "end_char": 1172, "text_sha256": "8542f3e0bd8f5903e6ce9e30fba2a6d7797a822ab1aeeab992659ba482533102", "text_characters": 1172} [mn-clin-davis1992b] Interactions among dietary manganese, heme iron, and nonheme iron in women. (1992). https://pubmed.ncbi.nlm.nih.gov/1415012/ DOI: 10.1093/ajcn/56.5.926
Complete structured claim and evidence
The genetic investigation linked SLC39A8 variants, very low blood manganese and type II glycosylation abnormalities.
Human SLC39A8 transport deficiency → Transferrin glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Human ZIP8 (SLC39A8) (affected_protein); Blood manganese concentration (specimen not further specified) (low_marker); UDP-galactose (related_substrate)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/park2015.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "c4e7009c947d1854370f8c9f62c206a8c2190b2e23099a5b991b01465321023d", "start_char": 0, "end_char": 1348, "text_sha256": "c4e7009c947d1854370f8c9f62c206a8c2190b2e23099a5b991b01465321023d", "text_characters": 1348}
experimental_model
Genetic investigation of two individuals with SLC39A8-CDG
exposure
Affected individuals with compound heterozygous SLC39A8 variants.
limitations
Inherited transport failure is distinct from dietary shortage. The study supports hypogalactosylation but does not directly measure activity of every manganese enzyme in every tissue.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
A transport defect can deprive sugar-building enzymes of manganese.
primary_references
[mn-clin-park2015] SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation. (2015). https://pubmed.ncbi.nlm.nih.gov/26637979/ DOI: 10.1016/j.ajhg.2015.11.003
tissue_or_cell_type
Blood manganese and serum glycoproteins
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1174–1186
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic investigation of two individuals with SLC39A8-CDG · source_derived_draft · unverified_draft
### mn-clin-zip8-glycosylation The genetic investigation linked SLC39A8 variants, very low blood manganese and type II glycosylation abnormalities. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transport defect can deprive sugar-building enzymes of manganese. organism: Homo sapiens tissue_or_cell_type: Blood manganese and serum glycoproteins experimental_model: Genetic investigation of two individuals with SLC39A8-CDG limitations: Inherited transport failure is distinct from dietary shortage. The study supports hypogalactosylation but does not directly measure activity of every manganese enzyme in every tissue. exposure: Affected individuals with compound heterozygous SLC39A8 variants. cross_nutrient: Human ZIP8 (SLC39A8) (affected_protein); Blood manganese concentration (specimen not further specified) (low_marker); UDP-galactose (related_substrate) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/park2015.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "c4e7009c947d1854370f8c9f62c206a8c2190b2e23099a5b991b01465321023d", "start_char": 0, "end_char": 1348, "text_sha256": "c4e7009c947d1854370f8c9f62c206a8c2190b2e23099a5b991b01465321023d", "text_characters": 1348} [mn-clin-park2015] SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation. (2015). https://pubmed.ncbi.nlm.nih.gov/26637979/ DOI: 10.1016/j.ajhg.2015.11.003
Complete structured claim and evidence
Manganese sulfate treatment corrected the measured biochemical dysfunctions, including glycosylation, in the two SLC39A8-deficient patients.
Manganese(II) sulfate → Transferrin glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Human ZIP8 (SLC39A8) (affected_protein); Manganese (administered_element)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/park2018.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "start_char": 0, "end_char": 1522, "text_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "text_characters": 1522}
experimental_model
Manganese treatment report in two patients with SLC39A8 deficiency
exposure
15 and 20 mg MnSO4/kg body weight/day as reported in the indexed abstract, with blood manganese, glycosylation and MRI monitoring.
limitations
Amounts describe manganese sulfate mass, not elemental manganese. Hydration state is not verified from this abstract, so no elemental conversion is made. Small uncontrolled rare-disease series; follow-up of previously described disease, not a general supplementation trial.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Supplying manganese improved the measured biochemical abnormalities in these patients.
primary_references
[mn-clin-park2018] SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy. (2018). https://pubmed.ncbi.nlm.nih.gov/28749473/ DOI: 10.1038/gim.2017.106
tissue_or_cell_type
Biochemical and neurological outcomes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1188–1200
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Manganese treatment report in two patients with SLC39A8 deficiency · source_derived_draft · unverified_draft
### mn-clin-zip8-manganese-biochemical Manganese sulfate treatment corrected the measured biochemical dysfunctions, including glycosylation, in the two SLC39A8-deficient patients. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying manganese improved the measured biochemical abnormalities in these patients. organism: Homo sapiens tissue_or_cell_type: Biochemical and neurological outcomes experimental_model: Manganese treatment report in two patients with SLC39A8 deficiency limitations: Amounts describe manganese sulfate mass, not elemental manganese. Hydration state is not verified from this abstract, so no elemental conversion is made. Small uncontrolled rare-disease series; follow-up of previously described disease, not a general supplementation trial. exposure: 15 and 20 mg MnSO4/kg body weight/day as reported in the indexed abstract, with blood manganese, glycosylation and MRI monitoring. cross_nutrient: Human ZIP8 (SLC39A8) (affected_protein); Manganese (administered_element) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/park2018.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "start_char": 0, "end_char": 1522, "text_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "text_characters": 1522} [mn-clin-park2018] SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy. (2018). https://pubmed.ncbi.nlm.nih.gov/28749473/ DOI: 10.1038/gim.2017.106
Complete structured claim and evidence
Motor abilities, hearing and other neurological manifestations improved during monitored manganese treatment in the two-patient report.
Manganese(II) sulfate → Measured neurological function source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Human ZIP8 (SLC39A8) (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/park2018.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "start_char": 0, "end_char": 1522, "text_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "text_characters": 1522}
experimental_model
Manganese treatment report in two patients with SLC39A8 deficiency
exposure
15 and 20 mg MnSO4/kg body weight/day as reported in the indexed abstract, with blood manganese, glycosylation and MRI monitoring.
limitations
Amounts describe manganese sulfate mass, not elemental manganese. Hydration state is not verified from this abstract, so no elemental conversion is made. Small uncontrolled rare-disease series; follow-up of previously described disease, not a general supplementation trial.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Biochemical improvement was accompanied by clinical improvement.
primary_references
[mn-clin-park2018] SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy. (2018). https://pubmed.ncbi.nlm.nih.gov/28749473/ DOI: 10.1038/gim.2017.106
tissue_or_cell_type
Biochemical and neurological outcomes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1202–1214
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Manganese treatment report in two patients with SLC39A8 deficiency · source_derived_draft · unverified_draft
### mn-clin-zip8-manganese-clinical Motor abilities, hearing and other neurological manifestations improved during monitored manganese treatment in the two-patient report. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biochemical improvement was accompanied by clinical improvement. organism: Homo sapiens tissue_or_cell_type: Biochemical and neurological outcomes experimental_model: Manganese treatment report in two patients with SLC39A8 deficiency limitations: Amounts describe manganese sulfate mass, not elemental manganese. Hydration state is not verified from this abstract, so no elemental conversion is made. Small uncontrolled rare-disease series; follow-up of previously described disease, not a general supplementation trial. exposure: 15 and 20 mg MnSO4/kg body weight/day as reported in the indexed abstract, with blood manganese, glycosylation and MRI monitoring. cross_nutrient: Human ZIP8 (SLC39A8) (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/park2018.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "start_char": 0, "end_char": 1522, "text_sha256": "30cd68e96efec971f2e431d24f5b2a45c680ce0b5efe572e30d76aee758563f5", "text_characters": 1522} [mn-clin-park2018] SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy. (2018). https://pubmed.ncbi.nlm.nih.gov/28749473/ DOI: 10.1038/gim.2017.106
Complete structured claim and evidence
Patient 1 had low liver complex IV and II+III activities, elevated complex I, borderline-low muscle complex IV and reduced pyruvate dehydrogenase activity.
Human SLC39A8 transport deficiency → Mitochondrial respiratory enzyme activities source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Human ZIP8 (SLC39A8) (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/riley2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "start_char": 0, "end_char": 1732, "text_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "text_characters": 1732}
experimental_model
Two sisters with homozygous SLC39A8 p.Cys113Ser
exposure
Respiratory-chain tests in patient 1; manganese and transferrin measurements and galactose-plus-uridine response in patient 2.
limitations
Measurements were not performed in both sisters interchangeably. The proposed SOD2 explanation was not directly demonstrated; manganese had only recently been added and cannot explain the already observed 14-day galactose/uridine response.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The affected child had several mitochondrial enzyme abnormalities, without proof that each enzyme directly requires manganese.
primary_references
[mn-clin-riley2017] A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. (2017). https://pubmed.ncbi.nlm.nih.gov/27995398/ DOI: 10.1007/s10545-016-0010-6
tissue_or_cell_type
Patient-specific liver, muscle and blood measurements
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1216–1228
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two sisters with homozygous SLC39A8 p.Cys113Ser · source_derived_draft · unverified_draft
### mn-clin-zip8-respiratory-chain Patient 1 had low liver complex IV and II+III activities, elevated complex I, borderline-low muscle complex IV and reduced pyruvate dehydrogenase activity. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The affected child had several mitochondrial enzyme abnormalities, without proof that each enzyme directly requires manganese. organism: Homo sapiens tissue_or_cell_type: Patient-specific liver, muscle and blood measurements experimental_model: Two sisters with homozygous SLC39A8 p.Cys113Ser limitations: Measurements were not performed in both sisters interchangeably. The proposed SOD2 explanation was not directly demonstrated; manganese had only recently been added and cannot explain the already observed 14-day galactose/uridine response. exposure: Respiratory-chain tests in patient 1; manganese and transferrin measurements and galactose-plus-uridine response in patient 2. cross_nutrient: Human ZIP8 (SLC39A8) (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/riley2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "start_char": 0, "end_char": 1732, "text_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "text_characters": 1732} [mn-clin-riley2017] A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. (2017). https://pubmed.ncbi.nlm.nih.gov/27995398/ DOI: 10.1007/s10545-016-0010-6
Complete structured claim and evidence
Galactose plus uridine improved patient 2’s transferrin isoform pattern within 14 days.
D-galactose and uridine coadministration → Transferrin glycosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
D-Galactose (coadministered_substrate); Uridine (coadministered_substrate); Human ZIP8 (SLC39A8) (affected_protein)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/riley2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "start_char": 0, "end_char": 1732, "text_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "text_characters": 1732}
experimental_model
Two sisters with homozygous SLC39A8 p.Cys113Ser
exposure
Respiratory-chain tests in patient 1; manganese and transferrin measurements and galactose-plus-uridine response in patient 2.
limitations
Measurements were not performed in both sisters interchangeably. The proposed SOD2 explanation was not directly demonstrated; manganese had only recently been added and cannot explain the already observed 14-day galactose/uridine response.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
A combined substrate-support treatment improved the measured sugar pattern.
primary_references
[mn-clin-riley2017] A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. (2017). https://pubmed.ncbi.nlm.nih.gov/27995398/ DOI: 10.1007/s10545-016-0010-6
tissue_or_cell_type
Patient-specific liver, muscle and blood measurements
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1230–1242
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two sisters with homozygous SLC39A8 p.Cys113Ser · source_derived_draft · unverified_draft
### mn-clin-zip8-gal-uridine Galactose plus uridine improved patient 2’s transferrin isoform pattern within 14 days. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A combined substrate-support treatment improved the measured sugar pattern. organism: Homo sapiens tissue_or_cell_type: Patient-specific liver, muscle and blood measurements experimental_model: Two sisters with homozygous SLC39A8 p.Cys113Ser limitations: Measurements were not performed in both sisters interchangeably. The proposed SOD2 explanation was not directly demonstrated; manganese had only recently been added and cannot explain the already observed 14-day galactose/uridine response. exposure: Respiratory-chain tests in patient 1; manganese and transferrin measurements and galactose-plus-uridine response in patient 2. cross_nutrient: D-Galactose (coadministered_substrate); Uridine (coadministered_substrate); Human ZIP8 (SLC39A8) (affected_protein) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/riley2017.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "start_char": 0, "end_char": 1732, "text_sha256": "31e4e33ec5601d443fb2d469b2e2c7d1fd89c611db0f41938b43007952d0f005", "text_characters": 1732} [mn-clin-riley2017] A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders. (2017). https://pubmed.ncbi.nlm.nih.gov/27995398/ DOI: 10.1007/s10545-016-0010-6
Complete structured claim and evidence
Oral galactose improved transferrin glycoform patterns and reduced hypogalactosylated serum N-glycans in the two TMEM165-CDG patients.
D-Galactose → Serum N-glycan galactosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Human TMEM165 deficiency (underlying_defect)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/tmem165patients.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3899c8a8d58b702858b7e1e74723d46a9825f4d7846b969ccf33db688fa16eac", "start_char": 0, "end_char": 2039, "text_sha256": "3899c8a8d58b702858b7e1e74723d46a9825f4d7846b969ccf33db688fa16eac", "text_characters": 2039}
experimental_model
Two unrelated patients with TMEM165-CDG
exposure
Oral D-galactose; indexed abstract reports 1 g/kg/day in individuals homozygous for c.792+182G>A.
limitations
Primary abstract used for these claims; this nominal amount is not a reconstruction of the full titration schedule. Cell manganese-rescue experiments in the same paper must not be recast as manganese treatment of the patients.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Galactose improved selected blood sugar-chain markers despite the genetic defect.
primary_references
[mn-clin-tmem165patients] Galactose Supplementation in Patients With TMEM165-CDG Rescues the Glycosylation Defects. (2017). https://pubmed.ncbi.nlm.nih.gov/28323990/ DOI: 10.1210/jc.2016-3443
tissue_or_cell_type
Serum glycosylation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1244–1256
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two unrelated patients with TMEM165-CDG · source_derived_draft · unverified_draft
### mn-clin-tmem165-gal-patients Oral galactose improved transferrin glycoform patterns and reduced hypogalactosylated serum N-glycans in the two TMEM165-CDG patients. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Galactose improved selected blood sugar-chain markers despite the genetic defect. organism: Homo sapiens tissue_or_cell_type: Serum glycosylation experimental_model: Two unrelated patients with TMEM165-CDG limitations: Primary abstract used for these claims; this nominal amount is not a reconstruction of the full titration schedule. Cell manganese-rescue experiments in the same paper must not be recast as manganese treatment of the patients. exposure: Oral D-galactose; indexed abstract reports 1 g/kg/day in individuals homozygous for c.792+182G>A. cross_nutrient: Human TMEM165 deficiency (underlying_defect) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/tmem165patients.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "3899c8a8d58b702858b7e1e74723d46a9825f4d7846b969ccf33db688fa16eac", "start_char": 0, "end_char": 2039, "text_sha256": "3899c8a8d58b702858b7e1e74723d46a9825f4d7846b969ccf33db688fa16eac", "text_characters": 2039} [mn-clin-tmem165patients] Galactose Supplementation in Patients With TMEM165-CDG Rescues the Glycosylation Defects. (2017). https://pubmed.ncbi.nlm.nih.gov/28323990/ DOI: 10.1210/jc.2016-3443
Complete structured claim and evidence
Inherited SLC30A10 dysfunction caused manganese accumulation with dystonia, polycythemia and variable hepatic involvement.
Human SLC30A10 transport deficiency → Brain manganese accumulation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Hepatic manganese accumulation (affected_site); Polycythemia (associated_endpoint); Manganese (accumulated_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/tuschl2012.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2f9189a6c46181f8b859a3e9815440d331870e6e4d78035218de33c46fa92e49", "start_char": 0, "end_char": 1389, "text_sha256": "2f9189a6c46181f8b859a3e9815440d331870e6e4d78035218de33c46fa92e49", "text_characters": 1389}
experimental_model
Genetic study of eight families with inherited hypermanganesemia
exposure
Homozygous SLC30A10 changes in affected individuals without environmental overexposure.
limitations
Clinical phenotype varies among individuals. The 2016 correction changes the family A deletion in Figure 1 to exons 3 and 4; it is an author correction, not a scientific conflict.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Failure of manganese handling can produce excess manganese rather than shortage.
primary_references
[mn-clin-tuschl2012] Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. (2012). https://pubmed.ncbi.nlm.nih.gov/22341972/ DOI: 10.1016/j.ajhg.2012.01.018
tissue_or_cell_type
Brain, liver and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1258–1270
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic study of eight families with inherited hypermanganesemia · source_derived_draft · unverified_draft
### mn-clin-slc30a10-patient-accumulation Inherited SLC30A10 dysfunction caused manganese accumulation with dystonia, polycythemia and variable hepatic involvement. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Failure of manganese handling can produce excess manganese rather than shortage. organism: Homo sapiens tissue_or_cell_type: Brain, liver and blood experimental_model: Genetic study of eight families with inherited hypermanganesemia limitations: Clinical phenotype varies among individuals. The 2016 correction changes the family A deletion in Figure 1 to exons 3 and 4; it is an author correction, not a scientific conflict. exposure: Homozygous SLC30A10 changes in affected individuals without environmental overexposure. cross_nutrient: Hepatic manganese accumulation (affected_site); Polycythemia (associated_endpoint); Manganese (accumulated_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/tuschl2012.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2f9189a6c46181f8b859a3e9815440d331870e6e4d78035218de33c46fa92e49", "start_char": 0, "end_char": 1389, "text_sha256": "2f9189a6c46181f8b859a3e9815440d331870e6e4d78035218de33c46fa92e49", "text_characters": 1389} [mn-clin-tuschl2012] Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. (2012). https://pubmed.ncbi.nlm.nih.gov/22341972/ DOI: 10.1016/j.ajhg.2012.01.018
Complete structured claim and evidence
Chelation increased urinary manganese and reduced blood manganese in the followed SLC30A10 patient.
Calcium disodium edetate → Urinary manganese excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Whole-blood manganese concentration (reduced_endpoint); Manganese (removed_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; initial calcium disodium edetate treatment", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 8926, "end_char": 9841, "text_sha256": "0bc6daa528aab341fb9d91dc543811ba24f7f8e904f084c085bafc1d4093113e", "text_characters": 915}
experimental_model
Ten-year longitudinal report of one SLC30A10 patient
exposure
Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate.
limitations
Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The treatment moved more manganese into urine.
primary_references
[mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
tissue_or_cell_type
Urine, blood, brain MRI and motor function
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1272–1284
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-year longitudinal report of one SLC30A10 patient · source_derived_draft · unverified_draft
### mn-clin-chelation-manganese-removal Chelation increased urinary manganese and reduced blood manganese in the followed SLC30A10 patient. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The treatment moved more manganese into urine. organism: Homo sapiens tissue_or_cell_type: Urine, blood, brain MRI and motor function experimental_model: Ten-year longitudinal report of one SLC30A10 patient limitations: Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement. exposure: Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate. cross_nutrient: Whole-blood manganese concentration (reduced_endpoint); Manganese (removed_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; initial calcium disodium edetate treatment", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 8926, "end_char": 9841, "text_sha256": "0bc6daa528aab341fb9d91dc543811ba24f7f8e904f084c085bafc1d4093113e", "text_characters": 915} [mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
Complete structured claim and evidence
Dystonia and brain MRI abnormalities improved during the longitudinal chelation treatment.
Calcium disodium edetate → Dystonia severity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Globus pallidus T1-weighted MRI signal (associated_endpoint)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "78edd20dcd2eaffac255ea725a64825ca18850475d25c7c29599b04351a52d12", "start_char": 0, "end_char": 1183, "text_sha256": "78edd20dcd2eaffac255ea725a64825ca18850475d25c7c29599b04351a52d12", "text_characters": 1183}
experimental_model
Ten-year longitudinal report of one SLC30A10 patient
exposure
Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate.
limitations
Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Removing accumulated manganese was accompanied by improved movement and imaging.
primary_references
[mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
tissue_or_cell_type
Urine, blood, brain MRI and motor function
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1286–1298
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-year longitudinal report of one SLC30A10 patient · source_derived_draft · unverified_draft
### mn-clin-chelation-clinical Dystonia and brain MRI abnormalities improved during the longitudinal chelation treatment. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing accumulated manganese was accompanied by improved movement and imaging. organism: Homo sapiens tissue_or_cell_type: Urine, blood, brain MRI and motor function experimental_model: Ten-year longitudinal report of one SLC30A10 patient limitations: Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement. exposure: Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate. cross_nutrient: Globus pallidus T1-weighted MRI signal (associated_endpoint) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "78edd20dcd2eaffac255ea725a64825ca18850475d25c7c29599b04351a52d12", "start_char": 0, "end_char": 1183, "text_sha256": "78edd20dcd2eaffac255ea725a64825ca18850475d25c7c29599b04351a52d12", "text_characters": 1183} [mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
Complete structured claim and evidence
Zinc concentration fell during chelation and zinc sulfate was added.
Calcium disodium edetate → Measured zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
Zinc (affected_nutrient); Manganese (target_of_treatment)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; zinc fell during chelation", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 9745, "end_char": 9841, "text_sha256": "7ef45c204f1cf372e58dcedb502d4047ace972fd9321bd2af7ccbda75d349439", "text_characters": 96}
experimental_model
Ten-year longitudinal report of one SLC30A10 patient
exposure
Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate.
limitations
Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Treatment aimed at manganese also lowered another essential mineral.
primary_references
[mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
tissue_or_cell_type
Urine, blood, brain MRI and motor function
trigger_kind
biomarker_context Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1300–1312
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-year longitudinal report of one SLC30A10 patient · source_derived_draft · unverified_draft
### mn-clin-chelation-zinc-loss Zinc concentration fell during chelation and zinc sulfate was added. Condition category: biomarker_context nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Treatment aimed at manganese also lowered another essential mineral. organism: Homo sapiens tissue_or_cell_type: Urine, blood, brain MRI and motor function experimental_model: Ten-year longitudinal report of one SLC30A10 patient limitations: Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement. exposure: Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate. cross_nutrient: Zinc (affected_nutrient); Manganese (target_of_treatment) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; zinc fell during chelation", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 9745, "end_char": 9841, "text_sha256": "7ef45c204f1cf372e58dcedb502d4047ace972fd9321bd2af7ccbda75d349439", "text_characters": 96} [mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
Complete structured claim and evidence
After more frequent chelation and added ferrous fumarate, blood manganese, MRI and liver findings improved; later iron dosing was reduced after serum iron rose excessively.
Manganese chelation with added oral iron → Whole-blood manganese concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Ferrous fumarate (added_treatment); Calcium disodium edetate (concurrent_treatment); Iron (interacting_nutrient); Manganese (affected_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; age 15–16 treatment changes", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 9842, "end_char": 10521, "text_sha256": "2da91cbaa297984ac1c90caf8701ce0a3f9a633b806ef4fff178b6ecc46c8aa1", "text_characters": 679}
experimental_model
Ten-year longitudinal report of one SLC30A10 patient
exposure
Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate.
limitations
Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
The combined regimen affected both manganese removal and iron status.
primary_references
[mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
tissue_or_cell_type
Urine, blood, brain MRI and motor function
trigger_kind
machinery_impairment Imported condition classification; unverified.
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1314–1326
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-year longitudinal report of one SLC30A10 patient · source_derived_draft · unverified_draft
### mn-clin-iron-chelation-combination After more frequent chelation and added ferrous fumarate, blood manganese, MRI and liver findings improved; later iron dosing was reduced after serum iron rose excessively. Condition category: machinery_impairment nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combined regimen affected both manganese removal and iron status. organism: Homo sapiens tissue_or_cell_type: Urine, blood, brain MRI and motor function experimental_model: Ten-year longitudinal report of one SLC30A10 patient limitations: Repeated observations in one previously described patient. Combined treatment changes prevent attribution of later benefit to iron alone; disease-specific treatment is not routine nutrient replacement. exposure: Calcium disodium edetate chelation; subsequent increase in chelation frequency and addition of oral ferrous fumarate. cross_nutrient: Ferrous fumarate (added_treatment); Calcium disodium edetate (concurrent_treatment); Iron (interacting_nutrient); Manganese (affected_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/stamelou2012.txt", "locator": "Clinical description; age 15–16 treatment changes", "file_sha256": "5d86a26fe564508fb382d1c8df61f531bfbaf06b69e2078b0999e3a3129555f6", "start_char": 9842, "end_char": 10521, "text_sha256": "2da91cbaa297984ac1c90caf8701ce0a3f9a633b806ef4fff178b6ecc46c8aa1", "text_characters": 679} [mn-clin-stamelou2012] Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder. (2012). https://pubmed.ncbi.nlm.nih.gov/22926781/ DOI: 10.1002/mds.25138
Complete structured claim and evidence
Whole-blood manganese and pallidal T1-weighted MRI signal changed with manganese administration and withdrawal; their correlation was r=0.7693.
Parenteral manganese administration → Globus pallidus T1-weighted MRI signal source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Whole-blood manganese concentration (correlated_marker); Manganese (administered_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/takagi2001.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "start_char": 0, "end_char": 1726, "text_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "text_characters": 1726}
experimental_model
On-off manganese study in 11 adults on home parenteral nutrition
exposure
Parenteral nutrition containing 0 or 20 micromoles Mn/day; serial blood and MRI measurements.
limitations
Intravenous exposure bypasses intestinal regulation. T1-weighted signal is a deposition-related marker, not by itself proof of neurological disability or a general dietary threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
Blood and brain imaging responded together under this intravenous exposure.
primary_references
[mn-clin-takagi2001] On-off study of manganese administration to adult patients undergoing home parenteral nutrition: new indices of in vivo manganese level. (2001). https://pubmed.ncbi.nlm.nih.gov/11284475/ DOI: 10.1177/014860710102500287
tissue_or_cell_type
Whole blood and brain MRI
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1328–1340
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · On-off manganese study in 11 adults on home parenteral nutrition · source_derived_draft · unverified_draft
### mn-clin-parenteral-marker-response Whole-blood manganese and pallidal T1-weighted MRI signal changed with manganese administration and withdrawal; their correlation was r=0.7693. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood and brain imaging responded together under this intravenous exposure. organism: Homo sapiens tissue_or_cell_type: Whole blood and brain MRI experimental_model: On-off manganese study in 11 adults on home parenteral nutrition limitations: Intravenous exposure bypasses intestinal regulation. T1-weighted signal is a deposition-related marker, not by itself proof of neurological disability or a general dietary threshold. exposure: Parenteral nutrition containing 0 or 20 micromoles Mn/day; serial blood and MRI measurements. cross_nutrient: Whole-blood manganese concentration (correlated_marker); Manganese (administered_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/takagi2001.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "start_char": 0, "end_char": 1726, "text_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "text_characters": 1726} [mn-clin-takagi2001] On-off study of manganese administration to adult patients undergoing home parenteral nutrition: new indices of in vivo manganese level. (2001). https://pubmed.ncbi.nlm.nih.gov/11284475/ DOI: 10.1177/014860710102500287
Complete structured claim and evidence
The increased T1-weighted signal took at least five months to disappear after manganese withdrawal.
Parenteral manganese administration → Globus pallidus T1-weighted MRI signal source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Manganese (withdrawn_nutrient)
evidence_span
{"source_cache": "artifacts/manganese-clinical-sources/takagi2001.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "start_char": 0, "end_char": 1726, "text_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "text_characters": 1726}
experimental_model
On-off manganese study in 11 adults on home parenteral nutrition
exposure
Parenteral nutrition containing 0 or 20 micromoles Mn/day; serial blood and MRI measurements.
limitations
Intravenous exposure bypasses intestinal regulation. T1-weighted signal is a deposition-related marker, not by itself proof of neurological disability or a general dietary threshold.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens
plain_language
A brain exposure marker could take months to return toward normal.
primary_references
[mn-clin-takagi2001] On-off study of manganese administration to adult patients undergoing home parenteral nutrition: new indices of in vivo manganese level. (2001). https://pubmed.ncbi.nlm.nih.gov/11284475/ DOI: 10.1177/014860710102500287
tissue_or_cell_type
Whole blood and brain MRI
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1342–1354
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · On-off manganese study in 11 adults on home parenteral nutrition · source_derived_draft · unverified_draft
### mn-clin-parenteral-mri-recovery The increased T1-weighted signal took at least five months to disappear after manganese withdrawal. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A brain exposure marker could take months to return toward normal. organism: Homo sapiens tissue_or_cell_type: Whole blood and brain MRI experimental_model: On-off manganese study in 11 adults on home parenteral nutrition limitations: Intravenous exposure bypasses intestinal regulation. T1-weighted signal is a deposition-related marker, not by itself proof of neurological disability or a general dietary threshold. exposure: Parenteral nutrition containing 0 or 20 micromoles Mn/day; serial blood and MRI measurements. cross_nutrient: Manganese (withdrawn_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/takagi2001.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "start_char": 0, "end_char": 1726, "text_sha256": "e5336a20271762ff7375cfe777c71c9b721c68bc47ae09e9a36b8eaac2953b8c", "text_characters": 1726} [mn-clin-takagi2001] On-off study of manganese administration to adult patients undergoing home parenteral nutrition: new indices of in vivo manganese level. (2001). https://pubmed.ncbi.nlm.nih.gov/11284475/ DOI: 10.1177/014860710102500287
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.

Mouse liver-specific Slc39a8 knockout genotype

Condition: machinery_impairment · Liver-specific Slc39a8 knockout versus controls.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Liver-specific Slc39a8 knockout lowered manganese in multiple organs and whole blood in mice. ZIP8-LSKO mice had increased bile manganese; ZIP8 localized to hepatocyte canalicular membranes, supporting biliary manganese reclamation.

Scope: Mus musculus; Mouse liver-specific Slc39a8 deletion and liver-directed human ZIP8 overexpression

Caco-2 SLC39A14 knockout genotype

Condition: machinery_impairment · ZIP14-deficient versus control Caco-2 Transwell monolayers.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: ZIP14 deletion in human Caco-2 Transwell cultures impaired basolateral-to-apical manganese transport. ZIP14 deletion in human Caco-2 Transwell cultures increased apical-to-basolateral manganese transport.

Scope: Homo sapiens; ZIP14-deficient human Caco-2 Transwell monolayers

Mouse liver-specific Slc39a14 knockout genotype

Condition: machinery_impairment · Liver-specific Slc39a14 knockout under normal study conditions.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Liver-specific Zip14 knockout reduced liver manganese without producing manganese accumulation in other tissues under the reported normal conditions.

Scope: Mus musculus; Liver-specific Slc39a14 knockout mice

Mouse intestine-specific Slc39a14 knockout genotype

Condition: machinery_impairment · Intestine-specific Slc39a14 knockout versus controls.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Intestine-specific Zip14 knockout increased liver and brain manganese in mice.

Scope: Mus musculus; Intestine-specific Slc39a14 knockout mice

Mouse whole-body Slc30a10 knockout genotype

Condition: machinery_impairment · Whole-body Slc30a10-deficient mice versus controls.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Whole-body Slc30a10 deficiency impaired systemic manganese excretion in mice.

Scope: Mus musculus; Whole-body and tissue-specific Slc30a10 knockout mice

Mouse hepatocyte-specific Slc30a10 knockout genotype

Condition: machinery_impairment · Liver-specific Slc30a10 deficiency versus controls.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Hepatic Slc30a10 deficiency impaired biliary manganese excretion in mice despite only minimal manganese excess.

Scope: Mus musculus; Whole-body and tissue-specific Slc30a10 knockout mice

Mouse small-intestine Slc30a10 knockout genotype

Condition: machinery_impairment · Small-intestine-specific Slc30a10 deficiency versus controls.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Small-intestinal Slc30a10 deficiency impaired manganese export into the intestinal lumen in mice despite minimal manganese excess.

Scope: Mus musculus; Whole-body and tissue-specific Slc30a10 knockout mice

Mouse liver-and-small-intestine Slc30a10 double-knockout genotype

Condition: machinery_impairment · Liver-and-small-intestine Slc30a10 deficiency compared with controls and whole-body deficiency.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Combined liver and small-intestine Slc30a10 deficiency caused manganese excess that was less severe than in whole-body deficient mice.

Scope: Mus musculus; Whole-body and tissue-specific Slc30a10 knockout mice

Mouse ZIP14 (Slc39a14)

Condition: machinery_impairment · ZIP14 siRNA versus controls during apical manganese exposure.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: ZIP14-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells.

Scope: Mus musculus; Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture

Mouse DMT1 (Slc11a2)

Condition: machinery_impairment · DMT1 siRNA versus controls during apical manganese exposure.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: DMT1-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells.

Scope: Mus musculus; Transporter-specific siRNA in polarized mouse kidney proximal-tubule culture

Mouse liver-and-intestine Slc39a14 double-knockout genotype

Condition: machinery_impairment · Intestine-and-liver double knockout versus single-tissue knockout and floxed controls.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Combined intestinal and hepatic Zip14 deletion increased systemic manganese burden more than intestinal deletion alone in mice.

Scope: Mus musculus; Single- and double-tissue Slc39a14 knockout mice; ICP-MS

ZIP8 suppression in renal cells

Condition: machinery_impairment · ZIP8 siRNA in polarized proximal-tubule cells

Normal role: ZIP8 provides multimetal entry capacity in the tested cellular system.

Recorded consequence: Reduced apical manganese uptake

Scope: Mus musculus; ZIP8 siRNA versus controls during apical manganese exposure.

Human SLC30A10 D40A mutant

Condition: machinery_impairment · D40A versus wild-type human SLC30A10 expression in HEK293T cells.

Normal role: Transporter activity contributes to manganese distribution or excretion in the specified system.

Recorded consequence: Human SLC30A10 D40A lost manganese transport function in the HEK293T assay compared with wild-type SLC30A10.

Scope: Homo sapiens; Site-directed SLC30A10 mutagenesis in HEK293T cells

Reduced manganese relative to iron alters mouse liver Sod2 metal loading

Condition: nutrient_deficiency · Four weeks of 40 ppm Mn/275 ppm Fe versus 150 ppm Mn/275 ppm Fe control.

Normal role: Manganese supports Sod2 dismutase chemistry.

Recorded consequence: More iron-loaded Sod2 and lower Sod2 dismutase activity.

Scope: Five-week-old male mice; author-described Mn-deprived natural-ingredient diet retains 40 ppm Mn.

Manganese delivery matters for sugar-chain construction

Condition: machinery_impairment · TMEM165 loss in the specified cells

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

Recorded consequence: Abnormal glycosylation can respond differently to manganese, galactose and the medium composition.

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

Golgi machinery loss impairs a cartilage-cell sugar chain

Condition: machinery_impairment · Tmem165 knockout in mouse ATDC5 cells

Normal role: Manganese handling supports glycosaminoglycan assembly.

Recorded consequence: Decorin GAG modification is impaired; manganese, but not galactose or xylose, rescued the measured phenotype.

Scope: Tmem165-knockout mouse ATDC5 chondrogenic cells

Mammary Golgi machinery changes milk composition

Condition: machinery_impairment · Conditional Tmem165 loss in mouse mammary epithelium

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

Recorded consequence: Lactose production falls and calcium/manganese normalized to milk protein are reduced.

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

Severe experimental manganese restriction

Condition: nutrient_deficiency · Controlled low-manganese purified diet

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

Recorded consequence: A skin eruption appeared in five of seven men; its specificity remains uncertain.

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

Iron stores change manganese absorption and retention

Condition: biomarker_context · Low versus high serum ferritin and altered manganese intake

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

Recorded consequence: Tracer absorption and retention differ with the combination of iron stores and diet.

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

When ZIP8 cannot supply enough manganese

Condition: machinery_impairment · Inherited SLC39A8 dysfunction

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

Recorded consequence: Very low manganese and impaired glycosylation, with patient-specific neurological findings.

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

Golgi machinery failure changes glycosylation

Condition: machinery_impairment · Inherited TMEM165 dysfunction

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

Recorded consequence: Serum glycan abnormalities may improve with galactose; this does not establish correction of every affected pathway.

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

Failure to excrete manganese causes accumulation

Condition: machinery_impairment · Inherited SLC30A10 dysfunction

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

Recorded consequence: Manganese accumulates with brain, liver and blood abnormalities.

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

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.

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
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
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
Selenium: literature corrections and mechanism additionsMetabolic Ledger literature curation, 17 September 2026; primary papers linked individually · secondary_verifiedRead 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.

Native ovine brain GLUL: manganese or magnesium?Published competing interpretations concern the same native cofactor question in ovine brain GLUL. The 1982 binding/kinetic study proposed a manganoenzyme; the 1986 cofactor-trapping study recovered predominantly Mg and favored Mg in vivo. Overlapping ovine brain enzyme and endogenous cofactor interpretation; 1986 additionally studied bovine brain. Methods differ. The conflict records competing published interpretations, not proof that identical assay results disagree. Neither paper determines living human brain GLUL occupancy.Read the recorded disagreement

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 blood measurements distinguish inadequate manganese supply from defective delivery into a particular organelle?Human feeding studies, rare transport disorders and intravenous exposure studies measure different pools; none supplies a universal cellular cutoff.
How often does ordinary dietary manganese deficiency cause clinically important disease in humans?A small controlled depletion study and rare genetic syndromes cannot establish population prevalence or attribute nonspecific symptoms to manganese.
Which separate contributions of galactose, uridine and manganese explain improvement in SLC39A8 deficiency?Small reports use different sequences and combinations. Corrected transferrin is not proof that every affected tissue or enzyme has recovered.
Predominant metal occupancy and nutritional Mn sensitivity of endogenous human brain GLUL remain unresolved by this source set.Human Mn-containing crystals establish binding capability; sheep/cattle native-cofactor studies offer competing interpretations.
Human nutritional conditions that cause clinically material iron loading of SOD2 are not established here.Direct dietary evidence is from mice; human protein experiments involve isolated enzyme, yeast expression or perturbed cells.
The Mg-depleted rat PC association does not show that Mn supplementation restores PC or that human PC obligatorily requires Mn.The study measured covariance rather than selective rescue; species and metal identity must remain separate.
Why does added galactose rescue some Golgi sugar-chain classes more effectively than others?Different enzyme affinities, compartmental substrate access and ion supply are candidate explanations. The measured rescue pattern does not independently validate one route.
Which combined manganese and substrate interventions improve whole-person outcomes in TMEM165 deficiency?Cellular Mn/galactose synergy and patient serum markers do not establish safe dosing or recovery of cartilage and other tissues.
How much renal ZIP8, ZIP14 and DMT1 individually contribute to manganese conservation in living humans remains unresolved by these polarized mouse-cell knockdown experiments.In vitro apical uptake does not directly measure whole-body renal reabsorption.
Iron and zinc inhibition of manganese transport through mouse ZIP14 does not by itself establish the size or direction of net dietary interactions in humans.Metal speciation, concentration, tissue and competing clearance routes differ.

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

Manganese

The mechanisms

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

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

Manganese acts as a cofactor in this reaction.

Reconstituted erythrocyte transketolase activity ranked Co2+ < Mn2+ < Ca2+ < Mg2+ in the tested assay.

COLGALT1 transfers galactose from UDP-galactose to collagen hydroxylysine.

Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay.

PLOD3 transfers glucose from UDP-glucose onto galactosyl-hydroxylysine in collagen.

PLOD3 hydroxylates peptidyl lysine using Fe(II), 2-oxoglutarate and oxygen.

Ascorbate supports sustained lysyl-hydroxylase activity; the enzyme can initially turn over without ascorbate.

Liver-specific Slc39a8 knockout lowered manganese in multiple organs and whole blood in mice.

Liver-directed AAV expression of human ZIP8 increased tissue and whole-blood manganese in mice.

ZIP8-LSKO mice had increased bile manganese; ZIP8 localized to hepatocyte canalicular membranes, supporting biliary manganese reclamation.

Liver-directed human ZIP8 overexpression decreased bile manganese in mice.

ZIP14 deletion in human Caco-2 Transwell cultures impaired basolateral-to-apical manganese transport.

ZIP14 deletion in human Caco-2 Transwell cultures increased apical-to-basolateral manganese transport.

Liver-specific Zip14 knockout reduced liver manganese without producing manganese accumulation in other tissues under the reported normal conditions.

Intestine-specific Zip14 knockout increased liver and brain manganese in mice.

Whole-body Slc30a10 deficiency impaired systemic manganese excretion in mice.

Hepatic Slc30a10 deficiency impaired biliary manganese excretion in mice despite only minimal manganese excess.

Small-intestinal Slc30a10 deficiency impaired manganese export into the intestinal lumen in mice despite minimal manganese excess.

Combined liver and small-intestine Slc30a10 deficiency caused manganese excess that was less severe than in whole-body deficient mice.

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

Fe(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions.

Zn(II) inhibited mouse ZIP14-mediated Mn(II) uptake in Xenopus oocytes under the tested competition conditions.

ZIP14-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells.

DMT1-specific siRNA reduced apical manganese uptake in polarized mouse proximal-tubule cells.

Combined intestinal and hepatic Zip14 deletion increased systemic manganese burden more than intestinal deletion alone in mice.

Cellular expression experiments identified human SLC30A10 as a cell-surface manganese efflux transporter.

The Mn-bound inward-facing human SLC30A10 cryo-EM structure placed Mn(II) at a site coordinated by D40, N127, D248 and S252.

Reconstituted human SLC30A10 transported Mn(II), while the same study detected no significant Zn(II), Ca(II) or Mg(II) transport under its tested conditions.

Human SLC30A10 D40A lost manganese transport function in the HEK293T assay compared with wild-type SLC30A10.

Neutron structures of human SOD2 captured Mn(III) and Mn(II) states with coupled changes in active-site protonation.

The human SOD2 active-site manganese is coordinated by His26, His74, His163, Asp159 and a water/hydroxide ligand in the structural model.

Human SOD2 uses a Mn(III)/Mn(II) cycle to convert superoxide into oxygen and hydrogen peroxide.

Human SOD1 maturation involves copper and zinc insertion and a Cys57–Cys146 disulfide; this is a different metalloprotein system from manganese SOD2.

At 30 °C, more than half of human SOD2 purified from expressing yeast mitochondria was apoprotein, and that apoprotein could be fully activated by reconstitution.

Increasing yeast growth temperature increased both manganese content and activity of mitochondrially expressed human SOD2.

Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments.

Mice fed the lower-manganese diet for four weeks had approximately 30% of isolated liver Sod2 iron-loaded, versus negligible iron loading in controls.

After four weeks on the iron-enriched diet, nearly 80% of isolated mouse liver Sod2 was iron-loaded.

Human ARG1 structures show a binuclear manganese site binding a boronate transition-state analogue, supporting metal stabilization of the arginine-hydrolysis transition state.

For reconstituted human ARG1, turnover and catalytic efficiency ranked Mn(II) > Ni(II) ≈ Co(II) ≫ Zn(II).

Added Zn(II) bound the H141/E277 region of manganese-loaded human ARG1, revealing a structural basis for zinc inhibition.

Purified recombinant human ARG2 catalyzes arginine hydrolysis to ornithine and urea.

The active truncated human ARG2 structure with a transition-state analogue supports a binuclear-manganese, metal-activated hydroxide mechanism for arginine hydrolysis.

Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine.

Human GLUL crystal structures contained Mn with ADP/phosphate or ADP/phosphorylated methionine-sulfoximine.

Ovine brain GLUL assays showed optimal Mg:ATP at 2:1 and Mn:ATP at 1:1, with different reported pH optima of 7.5 and 5.0, respectively.

From ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo.

Cofactor-trapped GLUL from bovine or ovine brain contained 1.5±0.2 Mg per subunit and less than 0.05 Mn per subunit.

The 1986 cofactor-trapping study concluded that Mg, rather than Mn, appears to be bound to bovine/ovine brain GLUL in vivo, although either metal supports assays.

Mg-depleted rats had lower manganese concentrations in plasma and every sampled tissue except adrenal glands and blood.

Mg depletion decreased liver crude-mitochondrial pyruvate-carboxylase activity; activity correlated positively with liver Mn concentration.

Human SPCA1a couples its ATPase cycle to manganese movement from cytosol into the Golgi lumen.

Human SPCA1a also transports calcium; calcium and manganese occupy the same transmembrane pocket in the respective structures.

In the manganese-containing bovine B4GALT1 complex, donor binding reorganized residues 345–365 and Trp314, creating the sugar-acceptor pocket.

Manganese supplementation restored glycosylation in the TMEM165-depleted mammalian-cell experiments.

MnCl2 restored the measured N-glycosylation phenotype in TMEM165-knockout HEK cells.

MnCl2 restored the measured O-linked glycosylation defects in TMEM165-knockout HEK cells.

MnCl2 restored the decorin glycosaminoglycan readout in mouse Tmem165-knockout ATDC5 cells.

D-galactose improved LAMP2 N-glycosylation only partially across the tested concentrations and times; the authors attributed residual underglycosylated protein to slow turnover.

D-galactose partially improved the 24-hour O-glycan lectin readout but failed to rescue the three-day benzyl-GalNAc mass-spectrometry phenotype in TMEM165-knockout HEK cells.

D-galactose did not rescue the decorin glycosaminoglycan defect in the tested mouse Tmem165-knockout ATDC5 cells.

Serum-lot composition changed the severity and manganese responsiveness of TMEM165-knockout glycosylation defects; manganese concentration alone did not explain all differences.

At 5 micromolar, both Fe(III) and Fe(II) produced partially glycosylated LAMP2 forms; manganese was more effective in the compared culture conditions.

With serum lot 4, combining 1 micromolar manganese and 1 millimolar galactose restored fully glycosylated LAMP2 more effectively than either alone.

Mammary epithelial Tmem165 deletion reduced lactose biosynthesis in lactating mice.

After normalization to milk protein, calcium and manganese were lower in milk from Tmem165-deficient dams.

The COLGALT1 GT2 catalytic site contains a Glu-Asp-Asp motif important for manganese binding.

Calcium and UDP-galactose bound in COLGALT1’s noncatalytic GT1 domain contribute to folding stability.

Pups nursed by mammary Tmem165-deficient dams had impaired growth.

Five of seven men developed miliaria crystallina during the depletion experiment; it disappeared as repletion began.

Plasma cholesterol fell during baseline as well as depletion and did not respond during the ten-day manganese repletion period.

Manganese absorption was greatest in the low-ferritin group on the low-manganese diet and lowest in the high-ferritin group.

Tracer half-life was longest with high ferritin and low manganese intake, and shortest during the high-manganese diets.

The high-ferritin group had lower measured arginase activity in the controlled dietary comparison.

Adding calcium to the human-milk test meal reduced manganese absorption in adults.

Iron added to the wheat-bread test meal did not significantly change manganese absorption.