Mn2+

evidence_access

Primary full text; Figure 3B

experimental_model

Recombinant human enzyme produced in bacterial expression culture.

limitations

This is not evidence that manganese supplements activate human agmatine breakdown; agmatine was not an accepted substrate.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

Metal handling during enzyme production affects measured activity.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme produced in bacterial expression culture. · source_derived_draft · unverified_draft

## agmatine-sulfate-agmat-manganese Metal handling during enzyme production affects measured activity. Expressing human AGMAT R105 in medium supplemented with 0.5 mM manganese increased its subsequent taurocyamine-hydrolysis activity approximately fourfold. Model: Recombinant human enzyme produced in bacterial expression culture. Limitations: This is not evidence that manganese supplements activate human agmatine breakdown; agmatine was not an accepted substrate. Evidence access: Primary full text; Figure 3B Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Recombinant rat protein, manganese activation and mutagenesis.

limitations

Mutations support residue importance but do not by themselves prove every proposed metal-coordination geometry.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

The metal-dependent catalytic machinery is a separate requirement from substrate supply.

primary_references

Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32531922/ · DOI 10.3390/ijms21114132

trigger_kind

machinery_impairment Imported condition classification; unverified.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 156–162

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant rat protein, manganese activation and mutagenesis. · source_derived_draft · unverified_draft

## agmatine-sulfate-rat-alp-metal The metal-dependent catalytic machinery is a separate requirement from substrate supply. Rat ALP catalytic activity required manganese; D217A and specified multi-residue substitutions abolished measured agmatinase activity. Model: Recombinant rat protein, manganese activation and mutagenesis. Limitations: Mutations support residue importance but do not by themselves prove every proposed metal-coordination geometry. Evidence access: Primary abstract Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32531922/ · DOI 10.3390/ijms21114132

evidence_access

Primary abstract

experimental_model

Dog kidney particulate-enzyme radiovanadate binding assay.

limitations

Assay concentrations and enzyme state matter; not a manganese supplementation interaction in humans.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

The supporting divalent ion changed inhibitor affinity.

primary_references

Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 230–236

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dog kidney particulate-enzyme radiovanadate binding assay. · source_derived_draft · unverified_draft

## vanadium-pump-mg-mn The supporting divalent ion changed inhibitor affinity. Replacing 3 mM MgCl2 with MnCl2 lowered vanadate-binding Kd from 96 to 12 nM in the dog-kidney Na/K-ATPase preparation without changing binding capacity. Model: Dog kidney particulate-enzyme radiovanadate binding assay. Limitations: Assay concentrations and enzyme state matter; not a manganese supplementation interaction in humans. Evidence access: Primary abstract Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

evidence_access

Primary abstract and linked primary deposited structure 5M4G

experimental_model

Human enzyme crystal structures, including deposited structure 5M4G at 1.48 angstroms.

limitations

Structural metal dependence does not establish that adding manganese improves recycling when manganese is already adequate.

nutrient_topic

L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline

plain_language

A mineral is part of the machinery that recycles proline from dipeptides.

primary_references

Substrate specificity and reaction mechanism of human prolidase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28677335/ · DOI 10.1111/febs.14158

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 270–276

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme crystal structures, including deposited structure 5M4G at 1.48 angstroms. · source_derived_draft · unverified_draft

## l-proline-pepd-manganese A mineral is part of the machinery that recycles proline from dipeptides. Human prolidase structures contain a binuclear manganese active site associated with the hydrolytic reaction; the study proposes hydroxide as the attacking catalytic species. Model: Human enzyme crystal structures, including deposited structure 5M4G at 1.48 angstroms. Limitations: Structural metal dependence does not establish that adding manganese improves recycling when manganese is already adequate. Evidence access: Primary abstract and linked primary deposited structure 5M4G Substrate specificity and reaction mechanism of human prolidase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28677335/ · DOI 10.1111/febs.14158

evidence_access

Primary abstract

experimental_model

Recombinant human CNDP2 characterization.

limitations

This does not show that manganese supplements lower carnosine in people.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

Manganese supports the enzyme’s measured activity.

primary_references

Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12473676/ · DOI 10.1074/jbc.M209764200

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 60–66

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human CNDP2 characterization. · source_derived_draft · unverified_draft

## carnosine-cndp2-manganese Manganese supports the enzyme’s measured activity. Adding Mn2+ was required for full recombinant CNDP2 dipeptidase activity. Model: Recombinant human CNDP2 characterization. Limitations: This does not show that manganese supplements lower carnosine in people. Evidence access: Primary abstract Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12473676/ · DOI 10.1074/jbc.M209764200

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

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

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

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

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

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

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

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

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

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

evidence_span

{"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"}

experimental_model

Purification and kinetics of placental PI synthase

exposure

Substrate and ion titrations

limitations

Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition.

nutrient_topic

Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)

organism

Homo sapiens

plain_language

Manganese was another supporting ion in the assay; this is not evidence that extra manganese is needed.

primary_references

[ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517

tissue_or_cell_type

Placental microsomal enzyme

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 522–533

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetics of placental PI synthase · source_derived_draft · unverified_draft

### ino-cdipt-manganese Mn2+ supported purified human placental PI synthase as an alternative activating divalent cation to Mg2+. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese was another supporting ion in the assay; this is not evidence that extra manganese is needed. organism: Homo sapiens tissue_or_cell_type: Placental microsomal enzyme experimental_model: Purification and kinetics of placental PI synthase limitations: Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition. exposure: Substrate and ion titrations evidence_span: {"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"} [ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517

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/)

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

evidence_span

{"source_cache": "artifacts/iron-research/9242408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52", "start_char": 0, "end_char": 1203, "text_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52"}

experimental_model

Cloning and functional expression of DCT1/DMT1

exposure

Metal-ion uptake, membrane potential and iron-deficient feeding

limitations

Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction.

nutrient_topic

Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron

organism

Rat transporter

plain_language

Iron shares this transporter with other metals, making the transport setting important.

primary_references

[iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343

tissue_or_cell_type

Transport assay and duodenal expression

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 407–418

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and functional expression of DCT1/DMT1 · source_derived_draft · unverified_draft

### iron-dmt-other-metals The original rat DCT1 expression assay also transported Mn(II), among other divalent metals. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron shares this transporter with other metals, making the transport setting important. organism: Rat transporter tissue_or_cell_type: Transport assay and duodenal expression experimental_model: Cloning and functional expression of DCT1/DMT1 limitations: Original broad substrate profile; later substrate-specific studies and species differences must be retained. Competition in an assay is not a universal dietary interaction. exposure: Metal-ion uptake, membrane potential and iron-deficient feeding evidence_span: {"source_cache": "artifacts/iron-research/9242408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52", "start_char": 0, "end_char": 1203, "text_sha256": "0b5241ac49e6de4e273c91f36387357c9bd76ce602e44defffc3b8b42191fe52"} [iron-p9242408] Cloning and characterization of a mammalian proton-coupled metal-ion transporter. (1997). https://pubmed.ncbi.nlm.nih.gov/9242408/ DOI: 10.1038/41343

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

evidence_access

Primary abstract

experimental_model

Dog kidney Na/K-ATPase binding experiments.

limitations

Effect was not appreciable under the manganese condition; not evidence that dietary potassium necessarily increases toxicity.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

Potassium can shift the pump toward an inhibitor-sensitive state.

primary_references

Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 238–244

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dog kidney Na/K-ATPase binding experiments. · source_derived_draft · unverified_draft

## vanadium-pump-potassium Potassium can shift the pump toward an inhibitor-sensitive state. In magnesium-containing medium, potassium increased vanadate binding and lowered its Kd to about 11 nM without changing maximum binding. Model: Dog kidney Na/K-ATPase binding experiments. Limitations: Effect was not appreciable under the manganese condition; not evidence that dietary potassium necessarily increases toxicity. Evidence access: Primary abstract Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

evidence_access

Primary abstract

experimental_model

Dog kidney enzyme binding assay.

limitations

No human dietary sodium recommendation follows.

nutrient_topic

Vanadium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Vanadium

plain_language

The ionic environment changes how vanadate interacts with the pump.

primary_references

Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 246–252

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Dog kidney enzyme binding assay. · source_derived_draft · unverified_draft

## vanadium-pump-sodium The ionic environment changes how vanadate interacts with the pump. Sodium decreased vanadate binding in magnesium-containing medium, whereas sodium and potassium had little effect in the manganese condition. Model: Dog kidney enzyme binding assay. Limitations: No human dietary sodium recommendation follows. Evidence access: Primary abstract Vanadate binding to the (Na + K)-ATPase. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6277881/ · DOI 10.1007/BF00743200

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

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

evidence_access

Primary abstract

experimental_model

Purified calf-brain enzyme.

limitations

Free-ion assay concentrations do not establish dietary antagonism.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

A mineral that activates one enzyme can inhibit another.

primary_references

Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 64–70

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified calf-brain enzyme. · source_derived_draft · unverified_draft

## lithium-inpp1-calcium-manganese A mineral that activates one enzyme can inhibit another. Calcium and manganese each inhibited the calf-brain enzyme by about half near 6 micromolar under the reported assay conditions. Model: Purified calf-brain enzyme. Limitations: Free-ion assay concentrations do not establish dietary antagonism. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

cell_type

experimental cells

experimental_model

Biochemical and cellular assays

limitations

Recent 2026 finding; no dietary-dose inference.

organism

mammalian

Selenium: literature corrections and mechanism additions · lines 438–448

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Biochemical and cellular assays · secondary_verified · secondary_verified

## selenoo-hydrolyzes-nad SELENOO can split NAD into two smaller molecules. SELENOO catalyzes NAD+ hydrolysis to NMN and AMP. Organism: mammalian Cell type: experimental cells Experimental model: Biochemical and cellular assays Limitations: Recent 2026 finding; no dietary-dose inference. Primary reference: [NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis](https://pubmed.ncbi.nlm.nih.gov/41806834/)