Nutrient chapter

Magnesium

Nutritional magnesium element; distinct from free Mg2+, salts and Mg-nucleotide complexes. Nutrient element magnesium; dietary supply is distinct from serum concentration, free intracellular Mg2+, and Mg-bound metabolites. The dietary nutrient element magnesium; distinct from free Mg2+ and Mg-nucleotide complexes. Nutritional magnesium element; distinguish intake, ionized pools, salts and Mg-nucleotide complexes.

154 recorded mechanisms · 36 availability situations · 10 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Cytoplasmic Mg2+ caused voltage-dependent reduction of ROMK1 outward single-channel current without reducing channel open probability.
Mg2+ → ROMK1 splice isoform source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> potassium
experimental_model
Heterologous channel expression and patch-clamp
limitations
Excised-patch channel behavior does not quantify whole-body potassium loss in humans.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Xenopus laevis host; mammalian ROMK channel
plain_language
Mg inside the cell can obstruct outward potassium flow through ROMK; this is a conduction effect, not evidence that the channel disappears.
primary_references
[nichols-1994-romk1] Mg(2+)-dependent inward rectification of ROMK1 potassium channels expressed in Xenopus oocytes (1994). https://pubmed.ncbi.nlm.nih.gov/8057249/ DOI: 10.1113/jphysiol.1994.sp020141
tissue_or_cell_type
Oocyte membrane
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 104–114
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous channel expression and patch-clamp · source_derived_draft · unverified_draft
### mg-romk1-outward-current-block Cytoplasmic Mg2+ caused voltage-dependent reduction of ROMK1 outward single-channel current without reducing channel open probability. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mg inside the cell can obstruct outward potassium flow through ROMK; this is a conduction effect, not evidence that the channel disappears. organism: Xenopus laevis host; mammalian ROMK channel tissue_or_cell_type: Oocyte membrane experimental_model: Heterologous channel expression and patch-clamp limitations: Excised-patch channel behavior does not quantify whole-body potassium loss in humans. cross_nutrient: magnesium -> potassium [nichols-1994-romk1] Mg(2+)-dependent inward rectification of ROMK1 potassium channels expressed in Xenopus oocytes (1994). https://pubmed.ncbi.nlm.nih.gov/8057249/ DOI: 10.1113/jphysiol.1994.sp020141
Complete structured claim and evidence
Lower external K+ increased the apparent affinity of cytoplasmic Mg2+ block of rat ROMK2 and permitted block over physiologically relevant negative voltages.
Potassium ion → ROMK2 splice isoform source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> potassium
experimental_model
Heterologous channel expression and patch-clamp
exposure
External K tested at 110, 11 and 1.1 mM; experimental concentrations, not dietary targets.
limitations
Excised-patch channel behavior does not quantify whole-body potassium loss in humans.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Xenopus laevis host; mammalian ROMK channel
plain_language
The potassium concentration outside the cell changes how strongly inside Mg restrains potassium exit.
primary_references
[yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
tissue_or_cell_type
Oocyte membrane
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 116–127
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous channel expression and patch-clamp · source_derived_draft · unverified_draft
### mg-romk2-low-external-k-enhances-block Lower external K+ increased the apparent affinity of cytoplasmic Mg2+ block of rat ROMK2 and permitted block over physiologically relevant negative voltages. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium concentration outside the cell changes how strongly inside Mg restrains potassium exit. organism: Xenopus laevis host; mammalian ROMK channel tissue_or_cell_type: Oocyte membrane experimental_model: Heterologous channel expression and patch-clamp limitations: Excised-patch channel behavior does not quantify whole-body potassium loss in humans. cross_nutrient: magnesium -> potassium exposure: External K tested at 110, 11 and 1.1 mM; experimental concentrations, not dietary targets. [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
Complete structured claim and evidence
Mg2+ supplied through the whole-cell pipette reduced tertiapin-Q-sensitive current in rat cortical collecting-duct principal cells.
Mg2+ → Renal outer medullary potassium channel / KCNJ1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> potassium
experimental_model
Whole-cell patch-clamp with controlled pipette Mg
limitations
Pipette-controlled Mg and voltage are not measurements of intracellular Mg during a human deficiency.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
Native kidney-cell recordings support the Mg brake on ROMK potassium flow seen in expressed channels.
primary_references
[yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
tissue_or_cell_type
Cortical collecting-duct principal cells
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 129–139
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell patch-clamp with controlled pipette Mg · source_derived_draft · unverified_draft
### mg-native-ccd-romk-current-block Mg2+ supplied through the whole-cell pipette reduced tertiapin-Q-sensitive current in rat cortical collecting-duct principal cells. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Native kidney-cell recordings support the Mg brake on ROMK potassium flow seen in expressed channels. organism: Rattus norvegicus tissue_or_cell_type: Cortical collecting-duct principal cells experimental_model: Whole-cell patch-clamp with controlled pipette Mg limitations: Pipette-controlled Mg and voltage are not measurements of intracellular Mg during a human deficiency. cross_nutrient: magnesium -> potassium [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
Complete structured claim and evidence
Extracellular Mg2+ also reduced ROMK2 single-channel current, with stronger apparent block as external K+ fell.
Mg2+ → ROMK2 splice isoform source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> potassium
experimental_model
Heterologous channel expression and patch-clamp
limitations
Excised-patch channel behavior does not quantify whole-body potassium loss in humans.
magnesium-pool
Extracellular free Mg2+
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Xenopus laevis host; mammalian ROMK channel
plain_language
Mg on the urine-facing side can also limit channel current; its action is separate from intracellular Mg.
primary_references
[yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
tissue_or_cell_type
Oocyte membrane
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 141–152
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous channel expression and patch-clamp · source_derived_draft · unverified_draft
### mg-extracellular-romk2-block Extracellular Mg2+ also reduced ROMK2 single-channel current, with stronger apparent block as external K+ fell. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mg on the urine-facing side can also limit channel current; its action is separate from intracellular Mg. organism: Xenopus laevis host; mammalian ROMK channel tissue_or_cell_type: Oocyte membrane experimental_model: Heterologous channel expression and patch-clamp limitations: Excised-patch channel behavior does not quantify whole-body potassium loss in humans. cross_nutrient: magnesium -> potassium magnesium-pool: Extracellular free Mg2+ [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
Complete structured claim and evidence
Mg restriction reduced cleaved alpha/gamma ENaC abundance and blunted amiloride-induced sodium excretion in mice.
Magnesium → Epithelial sodium channel source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> sodium -> potassium
experimental_model
Dietary restriction in C57BL/6J mice with renal transport assays
limitations
Cleaved subunits and amiloride response support ENaC inhibition; the molecular cause was unresolved.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
With less dietary Mg, these kidneys reduced the sodium entry pathway that normally helps drive potassium secretion.
primary_references
[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
tissue_or_cell_type
Kidney distal nephron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 154–164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft
### mg-restriction-reduces-enac-activity Mg restriction reduced cleaved alpha/gamma ENaC abundance and blunted amiloride-induced sodium excretion in mice. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: With less dietary Mg, these kidneys reduced the sodium entry pathway that normally helps drive potassium secretion. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Cleaved subunits and amiloride response support ENaC inhibition; the molecular cause was unresolved. cross_nutrient: magnesium -> sodium -> potassium [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
Complete structured claim and evidence
Isolated Mg restriction produced hypomagnesemia without the hypokalemia observed under combined Na/Mg restriction in the tested mice.
Magnesium → Serum or plasma potassium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> sodium -> potassium
experimental_model
Dietary restriction in C57BL/6J mice with renal transport assays
limitations
Model-specific non-sufficiency; not a claim that isolated Mg restriction can never lower K at other durations or in humans.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
A low Mg blood value alone did not guarantee falling potassium: sodium transport and the rest of the kidney response mattered.
primary_references
[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
tissue_or_cell_type
Kidney distal nephron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 166–176
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft
### mg-restriction-alone-not-sufficient-hypokalemia Isolated Mg restriction produced hypomagnesemia without the hypokalemia observed under combined Na/Mg restriction in the tested mice. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low Mg blood value alone did not guarantee falling potassium: sodium transport and the rest of the kidney response mattered. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Model-specific non-sufficiency; not a claim that isolated Mg restriction can never lower K at other durations or in humans. cross_nutrient: magnesium -> sodium -> potassium [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
Complete structured claim and evidence
Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet.
Magnesium → Renal outer medullary potassium channel / KCNJ1 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> sodium -> potassium
duration
Seven days
experimental_contrast
{"combination": "joint", "comparator": "Normal diet", "conditions": [{"entity_slug": "sodium", "state": "Restricted"}, {"entity_slug": "magnesium", "state": "Restricted"}], "effect_direction": "increase", "endpoint": "Native ROMK activity in DCT2/CNT", "intervention": "Combined dietary sodium and magnesium restriction"} Primary abstract PMID 41137719 / DOI 10.1113/JP287704 rechecked 2026-09-20. This comparison must not be separated into two single-deficiency effects.
experimental_model
Dietary restriction in C57BL/6J mice with renal transport assays
limitations
Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available.
primary_references
[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
tissue_or_cell_type
Kidney distal nephron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 178–189
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft
### combined-na-mg-restriction-romk-hypokalemia Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured. cross_nutrient: magnesium -> sodium -> potassium duration: Seven days [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
Complete structured claim and evidence
Plasma aldosterone in combined Na/Mg-restricted mice was not higher than with normal diet, although sodium restriction alone increased it.
Magnesium → Aldosterone source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> sodium -> potassium
experimental_model
Dietary restriction in C57BL/6J mice with renal transport assays
limitations
Unchanged concentration does not imply absent mineralocorticoid action or exclude other ENaC regulators.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
The potassium loss pattern did not require a measured rise in circulating aldosterone in this experiment.
primary_references
[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
tissue_or_cell_type
Kidney distal nephron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 191–201
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft
### combined-na-mg-restriction-aldosterone-not-elevated Plasma aldosterone in combined Na/Mg-restricted mice was not higher than with normal diet, although sodium restriction alone increased it. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium loss pattern did not require a measured rise in circulating aldosterone in this experiment. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Unchanged concentration does not imply absent mineralocorticoid action or exclude other ENaC regulators. cross_nutrient: magnesium -> sodium -> potassium [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704
Complete structured claim and evidence
The mouse findings support a model in which sustained ENaC sodium entry and higher ROMK conductance jointly favor potassium secretion during combined Na/Mg restriction.
Epithelial sodium channel → Distal renal potassium secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> sodium -> potassium
experimental_model
Dietary restriction in C57BL/6J mice with renal transport assays
limitations
Integrated mechanism supported across experiments; enhanced distal Na delivery was not demonstrated and is not required by these data.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
Sodium entry changes the electrical conditions for potassium exit; lifting the Mg brake on ROMK matters when that driving force is available.
primary_references
[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704 [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
spatial_transport_direction
Na+: tubular lumen to cell via ENaC; K+: cell to lumen via ROMK.
tissue_or_cell_type
Kidney distal nephron
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 203–215
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary restriction in C57BL/6J mice with renal transport assays · source_derived_draft · unverified_draft
### mg-romk-enac-conditional-k-secretory-chain The mouse findings support a model in which sustained ENaC sodium entry and higher ROMK conductance jointly favor potassium secretion during combined Na/Mg restriction. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sodium entry changes the electrical conditions for potassium exit; lifting the Mg brake on ROMK matters when that driving force is available. organism: Mus musculus tissue_or_cell_type: Kidney distal nephron experimental_model: Dietary restriction in C57BL/6J mice with renal transport assays limitations: Integrated mechanism supported across experiments; enhanced distal Na delivery was not demonstrated and is not required by these data. cross_nutrient: magnesium -> sodium -> potassium spatial_transport_direction: Na+: tubular lumen to cell via ENaC; K+: cell to lumen via ROMK. [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704 [yang-2010-romk-magnesium] Magnesium modulates ROMK channel-mediated potassium secretion (2010). https://pubmed.ncbi.nlm.nih.gov/21030597/ DOI: 10.1681/ASN.2010060617
Complete structured claim and evidence
Prolonged experimental Mg depletion caused hypokalemia requiring substantial extra potassium intake to maintain serum K, alongside decreased exchangeable potassium.
Magnesium → Potassium source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> potassium
experimental_model
Within-person dietary depletion and repletion
limitations
Two elderly men; no native human channel assay and no causal localization of potassium loss to ROMK.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Supplying potassium became less effective at maintaining potassium status as Mg depletion progressed.
primary_references
[shils-1964-human-depletion] Experimental Human Magnesium Depletion. I. Clinical Observations and Blood Chemistry Alterations (1964). https://pubmed.ncbi.nlm.nih.gov/14212747/ DOI: 10.1093/ajcn/15.3.133
tissue_or_cell_type
Blood and whole-body potassium pool
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 217–227
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person dietary depletion and repletion · source_derived_draft · unverified_draft
### human-mg-depletion-increases-k-replacement-needs Prolonged experimental Mg depletion caused hypokalemia requiring substantial extra potassium intake to maintain serum K, alongside decreased exchangeable potassium. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying potassium became less effective at maintaining potassium status as Mg depletion progressed. organism: Homo sapiens tissue_or_cell_type: Blood and whole-body potassium pool experimental_model: Within-person dietary depletion and repletion limitations: Two elderly men; no native human channel assay and no causal localization of potassium loss to ROMK. cross_nutrient: magnesium -> potassium [shils-1964-human-depletion] Experimental Human Magnesium Depletion. I. Clinical Observations and Blood Chemistry Alterations (1964). https://pubmed.ncbi.nlm.nih.gov/14212747/ DOI: 10.1093/ajcn/15.3.133
Complete structured claim and evidence
Serum potassium rose after Mg repletion in both men studied during prolonged experimental Mg depletion.
Magnesium → Serum or plasma potassium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> potassium
experimental_model
Within-person dietary depletion and repletion
limitations
Two elderly men; no native human channel assay and no causal localization of potassium loss to ROMK.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Restoring Mg improved potassium status in these depleted individuals; the experiment does not show that every low potassium result has this cause.
primary_references
[shils-1964-human-depletion] Experimental Human Magnesium Depletion. I. Clinical Observations and Blood Chemistry Alterations (1964). https://pubmed.ncbi.nlm.nih.gov/14212747/ DOI: 10.1093/ajcn/15.3.133
tissue_or_cell_type
Blood and whole-body potassium pool
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 229–239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Within-person dietary depletion and repletion · source_derived_draft · unverified_draft
### human-mg-repletion-restores-serum-k Serum potassium rose after Mg repletion in both men studied during prolonged experimental Mg depletion. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring Mg improved potassium status in these depleted individuals; the experiment does not show that every low potassium result has this cause. organism: Homo sapiens tissue_or_cell_type: Blood and whole-body potassium pool experimental_model: Within-person dietary depletion and repletion limitations: Two elderly men; no native human channel assay and no causal localization of potassium loss to ROMK. cross_nutrient: magnesium -> potassium [shils-1964-human-depletion] Experimental Human Magnesium Depletion. I. Clinical Observations and Blood Chemistry Alterations (1964). https://pubmed.ncbi.nlm.nih.gov/14212747/ DOI: 10.1093/ajcn/15.3.133
Complete structured claim and evidence
Randomized additional Mg sulfate improved 48-hour potassium input-minus-urine balance in hypokalemic ICU adults despite similar serum K; between-group total potassium replacement was not significantly different.
Magnesium → Potassium balance source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
magnesium -> potassium
experimental_model
Double-blind placebo-controlled randomized surgical-ICU trial
limitations
Usual K/Mg treatment continued in both groups; 30 completers; hypokalemia enrollment did not establish intracellular Mg depletion in every patient.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The Mg group retained more of the potassium supplied even though blood potassium looked similar. This supports retention, not a directly proven human ROMK mechanism.
primary_references
[hamill-ruth-1996-potassium-balance] Magnesium repletion and its effect on potassium homeostasis in critically ill adults: results of a double-blind, randomized, controlled trial. (1996). https://pubmed.ncbi.nlm.nih.gov/8565536/ DOI: 10.1097/00003246-199601000-00009
tissue_or_cell_type
Blood and timed urine collections
trigger_kind
biomarker_context Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 241–251
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled randomized surgical-ICU trial · source_derived_draft · unverified_draft
### icu-mg-repletion-improves-potassium-balance Randomized additional Mg sulfate improved 48-hour potassium input-minus-urine balance in hypokalemic ICU adults despite similar serum K; between-group total potassium replacement was not significantly different. Condition category: biomarker_context nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The Mg group retained more of the potassium supplied even though blood potassium looked similar. This supports retention, not a directly proven human ROMK mechanism. organism: Homo sapiens tissue_or_cell_type: Blood and timed urine collections experimental_model: Double-blind placebo-controlled randomized surgical-ICU trial limitations: Usual K/Mg treatment continued in both groups; 30 completers; hypokalemia enrollment did not establish intracellular Mg depletion in every patient. cross_nutrient: magnesium -> potassium [hamill-ruth-1996-potassium-balance] Magnesium repletion and its effect on potassium homeostasis in critically ill adults: results of a double-blind, randomized, controlled trial. (1996). https://pubmed.ncbi.nlm.nih.gov/8565536/ DOI: 10.1097/00003246-199601000-00009
Complete structured claim and evidence
In bovine parathyroid slices, extracellular Mg and Ca inhibited PTH release additively, but Mg was less potent on a molar basis.
Mg2+ → Parathyroid hormone secretion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Graded extracellular cations in cultured bovine parathyroid slices
limitations
Potency depends on concentrations and preparation; no general human replacement ratio follows.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Bos taurus
plain_language
Both ions can signal the gland to release less PTH; calcium and magnesium are not interchangeable inputs.
primary_references
[habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197
tissue_or_cell_type
Parathyroid gland
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 253–263
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Graded extracellular cations in cultured bovine parathyroid slices · source_derived_draft · unverified_draft
### mg-ca-differential-pth-secretory-potency In bovine parathyroid slices, extracellular Mg and Ca inhibited PTH release additively, but Mg was less potent on a molar basis. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Both ions can signal the gland to release less PTH; calcium and magnesium are not interchangeable inputs. organism: Bos taurus tissue_or_cell_type: Parathyroid gland experimental_model: Graded extracellular cations in cultured bovine parathyroid slices limitations: Potency depends on concentrations and preparation; no general human replacement ratio follows. cross_nutrient: magnesium -> PTH -> calcium [habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197
Complete structured claim and evidence
Mg concentration did not measurably change PTH biosynthesis or proPTH-to-PTH conversion in the bovine slice experiments.
Mg2+ → Parathyroid hormone biosynthesis source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Radiolabeled leucine incorporation and precursor/hormone analysis
limitations
A negative result in this exposure range does not exclude synthesis defects during prolonged severe deficiency.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Bos taurus
plain_language
Mg changed release of the hormone without showing the same effect on making or processing it in this assay.
primary_references
[habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197
tissue_or_cell_type
Parathyroid gland
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 265–275
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled leucine incorporation and precursor/hormone analysis · source_derived_draft · unverified_draft
### mg-does-not-change-pth-biosynthesis-in-slice-assay Mg concentration did not measurably change PTH biosynthesis or proPTH-to-PTH conversion in the bovine slice experiments. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mg changed release of the hormone without showing the same effect on making or processing it in this assay. organism: Bos taurus tissue_or_cell_type: Parathyroid gland experimental_model: Radiolabeled leucine incorporation and precursor/hormone analysis limitations: A negative result in this exposure range does not exclude synthesis defects during prolonged severe deficiency. cross_nutrient: magnesium -> PTH -> calcium [habener-1976-pth-synthesis-secretion] Relative effectiveness of magnesium and calcium on the secretion and biosynthesis of parathyroid hormone in vitro (1976). https://pubmed.ncbi.nlm.nih.gov/1248443/ DOI: 10.1210/endo-98-1-197
Complete structured claim and evidence
In intact rat glands, raising Mg from 0.5 to 2 mM suppressed PTH most clearly at moderately low Ca; suppression was small or absent at normal-high Ca and diminished again at very low Ca.
Mg2+ → Parathyroid hormone secretion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Intact rat parathyroid glands in graded Ca/Mg media
limitations
An ex-vivo concentration response, not a human threshold; very high 5 mM Mg produced broader suppression.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
How much extra Mg reduces PTH depends on the calcium signal already reaching the gland.
primary_references
[rodriguez-ortiz-2014-pth-context] Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration (2014). https://pubmed.ncbi.nlm.nih.gov/24103811/ DOI: 10.1093/ndt/gft400
tissue_or_cell_type
Parathyroid gland
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 277–287
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intact rat parathyroid glands in graded Ca/Mg media · source_derived_draft · unverified_draft
### mg-pth-inhibition-depends-on-calcium In intact rat glands, raising Mg from 0.5 to 2 mM suppressed PTH most clearly at moderately low Ca; suppression was small or absent at normal-high Ca and diminished again at very low Ca. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: How much extra Mg reduces PTH depends on the calcium signal already reaching the gland. organism: Rattus norvegicus tissue_or_cell_type: Parathyroid gland experimental_model: Intact rat parathyroid glands in graded Ca/Mg media limitations: An ex-vivo concentration response, not a human threshold; very high 5 mM Mg produced broader suppression. cross_nutrient: magnesium -> PTH -> calcium [rodriguez-ortiz-2014-pth-context] Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration (2014). https://pubmed.ncbi.nlm.nih.gov/24103811/ DOI: 10.1093/ndt/gft400
Complete structured claim and evidence
At 1.0 mM Ca, six-hour exposure to 2.0 versus 0.5 mM Mg increased CaSR mRNA and protein in intact rat glands.
Mg2+ → Calcium-sensing receptor / CaSR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
magnesium -> calcium sensing
experimental_model
Six-hour ex-vivo gland incubation with receptor expression assays
limitations
Receptor abundance alone does not prove altered clinical calcium balance; VDR, FGFR1 and Klotho also rose in this experiment.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
Mg exposure can change the amount of the calcium-sensing receptor, adding a slower response to immediate ion sensing.
primary_references
[rodriguez-ortiz-2014-pth-context] Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration (2014). https://pubmed.ncbi.nlm.nih.gov/24103811/ DOI: 10.1093/ndt/gft400
tissue_or_cell_type
Parathyroid gland
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 289–299
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-hour ex-vivo gland incubation with receptor expression assays · source_derived_draft · unverified_draft
### mg-increases-parathyroid-casr-expression At 1.0 mM Ca, six-hour exposure to 2.0 versus 0.5 mM Mg increased CaSR mRNA and protein in intact rat glands. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mg exposure can change the amount of the calcium-sensing receptor, adding a slower response to immediate ion sensing. organism: Rattus norvegicus tissue_or_cell_type: Parathyroid gland experimental_model: Six-hour ex-vivo gland incubation with receptor expression assays limitations: Receptor abundance alone does not prove altered clinical calcium balance; VDR, FGFR1 and Klotho also rose in this experiment. cross_nutrient: magnesium -> calcium sensing [rodriguez-ortiz-2014-pth-context] Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration (2014). https://pubmed.ncbi.nlm.nih.gov/24103811/ DOI: 10.1093/ndt/gft400
Complete structured claim and evidence
Most untreated patients in the clinical series had normal or undetectable immunoreactive PTH despite severe hypocalcemia.
Magnesium → Serum PTH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Human hypomagnesemic hypocalcemia clinical study
limitations
Observational baseline result; older immunoreactive PTH assays differ from modern intact-PTH methods.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A PTH value within a laboratory reference range can still be too low for someone whose calcium is very low.
primary_references
[rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
tissue_or_cell_type
Blood; parathyroid-kidney axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 301–311
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hypomagnesemic hypocalcemia clinical study · source_derived_draft · unverified_draft
### severe-mg-deficiency-inadequate-pth-response Most untreated patients in the clinical series had normal or undetectable immunoreactive PTH despite severe hypocalcemia. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A PTH value within a laboratory reference range can still be too low for someone whose calcium is very low. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid-kidney axis experimental_model: Human hypomagnesemic hypocalcemia clinical study limitations: Observational baseline result; older immunoreactive PTH assays differ from modern intact-PTH methods. cross_nutrient: magnesium -> PTH -> calcium [rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
Complete structured claim and evidence
Acute Mg administration increased circulating immunoreactive PTH within one minute in the three tested Mg-deficient patients.
Magnesium → Serum PTH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Human hypomagnesemic hypocalcemia clinical study
limitations
Three infusion experiments; timing supports but does not directly visualize secretory machinery.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The fast hormone rise supports release of stored PTH after Mg restoration, rather than requiring new hormone synthesis first.
primary_references
[rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
tissue_or_cell_type
Blood; parathyroid-kidney axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 313–323
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hypomagnesemic hypocalcemia clinical study · source_derived_draft · unverified_draft
### mg-repletion-rapidly-releases-pth Acute Mg administration increased circulating immunoreactive PTH within one minute in the three tested Mg-deficient patients. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fast hormone rise supports release of stored PTH after Mg restoration, rather than requiring new hormone synthesis first. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid-kidney axis experimental_model: Human hypomagnesemic hypocalcemia clinical study limitations: Three infusion experiments; timing supports but does not directly visualize secretory machinery. cross_nutrient: magnesium -> PTH -> calcium [rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
Complete structured claim and evidence
During early Mg repletion, PTH recovered before serum calcium normalized in the serially studied patients.
Serum PTH concentration → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Human hypomagnesemic hypocalcemia clinical study
limitations
Delay is indirect evidence for resistance and does not by itself identify a receptor or cyclase defect.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Restoring the hormone signal did not immediately restore calcium; this pattern suggested an additional target-organ response problem.
primary_references
[rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
tissue_or_cell_type
Blood; parathyroid-kidney axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 325–335
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hypomagnesemic hypocalcemia clinical study · source_derived_draft · unverified_draft
### calcium-recovery-can-lag-pth-after-mg During early Mg repletion, PTH recovered before serum calcium normalized in the serially studied patients. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring the hormone signal did not immediately restore calcium; this pattern suggested an additional target-organ response problem. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid-kidney axis experimental_model: Human hypomagnesemic hypocalcemia clinical study limitations: Delay is indirect evidence for resistance and does not by itself identify a receptor or cyclase defect. cross_nutrient: magnesium -> PTH -> calcium [rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
Complete structured claim and evidence
Parathyroid extract produced only a small urinary cAMP response in the two Mg-deficient patients tested, while glucagon-stimulated plasma cAMP responses were preserved.
Parathyroid hormone / PTH → Urinary cyclic AMP excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Human hypomagnesemic hypocalcemia clinical study
limitations
Only two challenge studies; urinary cAMP is an organ-response marker, not direct measurement of PTH1R binding or adenylyl-cyclase Mg occupancy.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The kidney responded weakly to the PTH challenge, but another hormone/cAMP response remained functional; Mg deficiency did not disable all signaling equally.
primary_references
[rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
tissue_or_cell_type
Blood; parathyroid-kidney axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 337–347
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human hypomagnesemic hypocalcemia clinical study · source_derived_draft · unverified_draft
### mg-deficiency-blunts-renal-pth-camp-response Parathyroid extract produced only a small urinary cAMP response in the two Mg-deficient patients tested, while glucagon-stimulated plasma cAMP responses were preserved. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney responded weakly to the PTH challenge, but another hormone/cAMP response remained functional; Mg deficiency did not disable all signaling equally. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid-kidney axis experimental_model: Human hypomagnesemic hypocalcemia clinical study limitations: Only two challenge studies; urinary cAMP is an organ-response marker, not direct measurement of PTH1R binding or adenylyl-cyclase Mg occupancy. cross_nutrient: magnesium -> PTH -> calcium [rude-1976-human-pth-resistance] Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human magnesium deficiency (1976). https://pubmed.ncbi.nlm.nih.gov/182417/ DOI: 10.1111/j.1365-2265.1976.tb01947.x
Complete structured claim and evidence
Mg administration promptly raised PTH in hypomagnesemic patients, whereas normal and hyperparathyroid comparison groups showed a decrease or little change.
Magnesium → Serum PTH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
Acute Mg administration across clinical groups
limitations
Biphasic/status-dependent response does not establish one serum Mg breakpoint applicable to all patients.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Restoring missing Mg can release a suppressed PTH response, while adding Mg in another starting state can inhibit it.
primary_references
[rude-1978-status-dependent-pth] Parathyroid hormone secretion in magnesium deficiency (1978). https://pubmed.ncbi.nlm.nih.gov/263326/ DOI: 10.1210/jcem-47-4-800
tissue_or_cell_type
Blood; parathyroid axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 349–359
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute Mg administration across clinical groups · source_derived_draft · unverified_draft
### mg-pth-response-depends-on-prior-status Mg administration promptly raised PTH in hypomagnesemic patients, whereas normal and hyperparathyroid comparison groups showed a decrease or little change. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring missing Mg can release a suppressed PTH response, while adding Mg in another starting state can inhibit it. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid axis experimental_model: Acute Mg administration across clinical groups limitations: Biphasic/status-dependent response does not establish one serum Mg breakpoint applicable to all patients. cross_nutrient: magnesium -> PTH -> calcium [rude-1978-status-dependent-pth] Parathyroid hormone secretion in magnesium deficiency (1978). https://pubmed.ncbi.nlm.nih.gov/263326/ DOI: 10.1210/jcem-47-4-800
Complete structured claim and evidence
After selective dietary Mg depletion, 20 of 26 adults showed unchanged or reduced PTH despite falling serum Mg and Ca.
Magnesium → Serum PTH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH -> calcium
experimental_model
26 initially normal adults before/after three-week low-Mg diet
limitations
Before/after experiment; not a population diagnostic rule. Depletion was supported by serum Mg, retention, and red-cell free Mg changes.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
PTH compensation was impaired during an induced shortage, before a failed calcium-replacement attempt was needed to reveal it.
primary_references
[fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067
tissue_or_cell_type
Blood; parathyroid and renal mineral axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 361–371
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26 initially normal adults before/after three-week low-Mg diet · source_derived_draft · unverified_draft
### selective-mg-depletion-impairs-pth-compensation After selective dietary Mg depletion, 20 of 26 adults showed unchanged or reduced PTH despite falling serum Mg and Ca. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PTH compensation was impaired during an induced shortage, before a failed calcium-replacement attempt was needed to reveal it. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid and renal mineral axis experimental_model: 26 initially normal adults before/after three-week low-Mg diet limitations: Before/after experiment; not a population diagnostic rule. Depletion was supported by serum Mg, retention, and red-cell free Mg changes. cross_nutrient: magnesium -> PTH -> calcium [fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067
Complete structured claim and evidence
Three weeks of selective Mg depletion produced a small but significant reduction in serum calcium in the adult study.
Magnesium → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> calcium
experimental_model
26 initially normal adults before/after three-week low-Mg diet
limitations
Mean change in a small controlled study; not evidence that every mildly low Mg value causes clinical hypocalcemia.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Calcium regulation changed during experimental Mg shortage even without a preceding calcium-repletion failure.
primary_references
[fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067
tissue_or_cell_type
Blood; parathyroid and renal mineral axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 373–383
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26 initially normal adults before/after three-week low-Mg diet · source_derived_draft · unverified_draft
### selective-mg-depletion-lowers-circulating-calcium Three weeks of selective Mg depletion produced a small but significant reduction in serum calcium in the adult study. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium regulation changed during experimental Mg shortage even without a preceding calcium-repletion failure. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid and renal mineral axis experimental_model: 26 initially normal adults before/after three-week low-Mg diet limitations: Mean change in a small controlled study; not evidence that every mildly low Mg value causes clinical hypocalcemia. cross_nutrient: magnesium -> calcium [fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067
Complete structured claim and evidence
The rise in circulating calcitriol during a six-hour human PTH(1-34) infusion was smaller after dietary Mg depletion.
Parathyroid hormone / PTH → Calcitriol source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH response -> vitamin D/calcium
experimental_model
26 initially normal adults before/after three-week low-Mg diet
limitations
Circulating metabolite response does not identify CYP27B1 as a directly Mg-dependent enzyme or distinguish all production/clearance effects.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Even when PTH was supplied directly, the downstream vitamin-D response was reduced, supporting a target-organ component beyond reduced hormone release.
primary_references
[fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067
tissue_or_cell_type
Blood; parathyroid and renal mineral axis
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 385–395
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 26 initially normal adults before/after three-week low-Mg diet · source_derived_draft · unverified_draft
### selective-mg-depletion-blunts-pth-calcitriol-response The rise in circulating calcitriol during a six-hour human PTH(1-34) infusion was smaller after dietary Mg depletion. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Even when PTH was supplied directly, the downstream vitamin-D response was reduced, supporting a target-organ component beyond reduced hormone release. organism: Homo sapiens tissue_or_cell_type: Blood; parathyroid and renal mineral axis experimental_model: 26 initially normal adults before/after three-week low-Mg diet limitations: Circulating metabolite response does not identify CYP27B1 as a directly Mg-dependent enzyme or distinguish all production/clearance effects. cross_nutrient: magnesium -> PTH response -> vitamin D/calcium [fatemi-1991-selective-depletion] Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. (1991). https://pubmed.ncbi.nlm.nih.gov/1939521/ DOI: 10.1210/jcem-73-5-1067
Complete structured claim and evidence
A child with primary hypomagnesemia retained calcemic and renal phosphate/cAMP responses to parathyroid extract during Mg depletion despite impaired endogenous PTH secretion.
Parathyroid hormone / PTH → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> PTH -> calcium/phosphate
experimental_model
Single-child Mg withdrawal/repletion with hormone challenge
limitations
Single case; shows PTH resistance is not obligatory. Primary hypomagnesemia was not genetically assigned in this study.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
In this child the main failure was releasing the hormone; tissues could still respond when hormone was provided.
primary_references
[suh-1973-preserved-pth-response] Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function (1973). https://www.jci.org/articles/view/107159 DOI: 10.1172/JCI107159
tissue_or_cell_type
Blood and kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 397–407
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-child Mg withdrawal/repletion with hormone challenge · source_derived_draft · unverified_draft
### primary-hypomagnesemia-can-preserve-pth-response A child with primary hypomagnesemia retained calcemic and renal phosphate/cAMP responses to parathyroid extract during Mg depletion despite impaired endogenous PTH secretion. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this child the main failure was releasing the hormone; tissues could still respond when hormone was provided. organism: Homo sapiens tissue_or_cell_type: Blood and kidney experimental_model: Single-child Mg withdrawal/repletion with hormone challenge limitations: Single case; shows PTH resistance is not obligatory. Primary hypomagnesemia was not genetically assigned in this study. cross_nutrient: magnesium -> PTH -> calcium/phosphate [suh-1973-preserved-pth-response] Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function (1973). https://www.jci.org/articles/view/107159 DOI: 10.1172/JCI107159
Complete structured claim and evidence
Lowering extracellular Mg to 0.1 mM suppressed PTH release from dispersed human parathyroid cells in the tested media.
Mg2+ → Parathyroid hormone secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> CaSR/PTH -> calcium
experimental_model
Dispersed human parathyroid cells from hyperparathyroid tissue
limitations
Experiment used hyperparathyroid tissue; culture concentrations are not clinical deficiency cutoffs.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
At very low Mg, the gland cells released less PTH even though simple loss of an inhibitory extracellular ion might predict more release.
primary_references
[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
tissue_or_cell_type
Parathyroid cells in vitro
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 409–419
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dispersed human parathyroid cells from hyperparathyroid tissue · source_derived_draft · unverified_draft
### very-low-mg-suppresses-pth-in-human-cells Lowering extracellular Mg to 0.1 mM suppressed PTH release from dispersed human parathyroid cells in the tested media. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: At very low Mg, the gland cells released less PTH even though simple loss of an inhibitory extracellular ion might predict more release. organism: Homo sapiens tissue_or_cell_type: Parathyroid cells in vitro experimental_model: Dispersed human parathyroid cells from hyperparathyroid tissue limitations: Experiment used hyperparathyroid tissue; culture concentrations are not clinical deficiency cutoffs. cross_nutrient: magnesium -> CaSR/PTH -> calcium [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
Complete structured claim and evidence
Low extracellular Mg increased inositol-phosphate generation in parathyroid cells; CaSR-expressing HEK-293 cells reproduced the enhancement.
Mg2+ → Inositol phosphates source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> CaSR/PTH -> calcium
experimental_model
Dispersed human parathyroid cells from hyperparathyroid tissue
limitations
The collective assay did not separately quantify every inositol-phosphate species; tissue disease and recombinant expression constrain transfer.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The calcium-sensing pathway became more active under low Mg in these cell experiments.
primary_references
[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
tissue_or_cell_type
Parathyroid cells in vitro
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 421–431
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dispersed human parathyroid cells from hyperparathyroid tissue · source_derived_draft · unverified_draft
### very-low-mg-enhances-inositol-phosphates Low extracellular Mg increased inositol-phosphate generation in parathyroid cells; CaSR-expressing HEK-293 cells reproduced the enhancement. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The calcium-sensing pathway became more active under low Mg in these cell experiments. organism: Homo sapiens tissue_or_cell_type: Parathyroid cells in vitro experimental_model: Dispersed human parathyroid cells from hyperparathyroid tissue limitations: The collective assay did not separately quantify every inositol-phosphate species; tissue disease and recombinant expression constrain transfer. cross_nutrient: magnesium -> CaSR/PTH -> calcium [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
Complete structured claim and evidence
Low Mg enhanced CaSR-associated inhibition of cAMP in the tested parathyroid and receptor-expression cell systems.
Mg2+ → Cyclic adenosine monophosphate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> CaSR/PTH -> calcium
experimental_model
Dispersed human parathyroid cells from hyperparathyroid tissue
limitations
This is pathway-dependent inhibition, not proof that every cellular adenylyl cyclase fails whenever Mg is low.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Low Mg strengthened a signaling arm that reduces the cAMP signal associated with PTH release.
primary_references
[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
tissue_or_cell_type
Parathyroid cells in vitro
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 433–443
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dispersed human parathyroid cells from hyperparathyroid tissue · source_derived_draft · unverified_draft
### very-low-mg-enhances-casr-camp-inhibition Low Mg enhanced CaSR-associated inhibition of cAMP in the tested parathyroid and receptor-expression cell systems. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low Mg strengthened a signaling arm that reduces the cAMP signal associated with PTH release. organism: Homo sapiens tissue_or_cell_type: Parathyroid cells in vitro experimental_model: Dispersed human parathyroid cells from hyperparathyroid tissue limitations: This is pathway-dependent inhibition, not proof that every cellular adenylyl cyclase fails whenever Mg is low. cross_nutrient: magnesium -> CaSR/PTH -> calcium [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
Complete structured claim and evidence
Pertussis-toxin pretreatment abolished the suppression of PTH release by low Mg in the parathyroid-cell assay.
Pertussis toxin → Parathyroid hormone secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> CaSR/PTH -> calcium
experimental_model
Dispersed human parathyroid cells from hyperparathyroid tissue
limitations
Pharmacologic pathway probe, not evidence for toxin use in patients; no full in-vivo chain tested.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Blocking Gi/o signaling removed the low-Mg secretory brake, placing these signaling proteins in the experimental pathway.
primary_references
[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
tissue_or_cell_type
Parathyroid cells in vitro
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 445–455
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dispersed human parathyroid cells from hyperparathyroid tissue · source_derived_draft · unverified_draft
### pertussis-toxin-removes-low-mg-pth-block Pertussis-toxin pretreatment abolished the suppression of PTH release by low Mg in the parathyroid-cell assay. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking Gi/o signaling removed the low-Mg secretory brake, placing these signaling proteins in the experimental pathway. organism: Homo sapiens tissue_or_cell_type: Parathyroid cells in vitro experimental_model: Dispersed human parathyroid cells from hyperparathyroid tissue limitations: Pharmacologic pathway probe, not evidence for toxin use in patients; no full in-vivo chain tested. cross_nutrient: magnesium -> CaSR/PTH -> calcium [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
Complete structured claim and evidence
Reconstituted G-protein assays supported Mg-dependent restraint of Galpha nucleotide exchange; reduced Mg enhanced signaling associated with basal CaSR activity.
Mg2+ → G protein alpha guanine-nucleotide exchange source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
magnesium -> CaSR/PTH -> calcium
experimental_model
CaSR-expressing HEK-293 membranes reconstituted with G proteins
limitations
Mechanistic explanation supported by probes; not an established sole cause of human hypomagnesemic hypocalcemia.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human receptor-expression system with purified/recombinant G proteins
plain_language
Less Mg can loosen the restraint on the G-protein switch, allowing the receptor pathway to suppress PTH more strongly.
primary_references
[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
tissue_or_cell_type
Reconstituted membrane signaling system
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 457–467
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CaSR-expressing HEK-293 membranes reconstituted with G proteins · source_derived_draft · unverified_draft
### low-mg-galpha-exchange-explains-paradox Reconstituted G-protein assays supported Mg-dependent restraint of Galpha nucleotide exchange; reduced Mg enhanced signaling associated with basal CaSR activity. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less Mg can loosen the restraint on the G-protein switch, allowing the receptor pathway to suppress PTH more strongly. organism: Human receptor-expression system with purified/recombinant G proteins tissue_or_cell_type: Reconstituted membrane signaling system experimental_model: CaSR-expressing HEK-293 membranes reconstituted with G proteins limitations: Mechanistic explanation supported by probes; not an established sole cause of human hypomagnesemic hypocalcemia. cross_nutrient: magnesium -> CaSR/PTH -> calcium [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
Complete structured claim and evidence
The low-Mg enhancement of CaSR-stimulated GTP analogue binding was lost with the reduced-Mg-sensitivity Galpha-i1 R209C mutant; changing receptor extracellular cation affinity did not remove it.
GNAI1 R209C experimental mutant → G protein alpha guanine-nucleotide exchange source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
magnesium -> CaSR/PTH -> calcium
experimental_model
Engineered receptor and Galpha comparison in reconstituted signaling assays
limitations
Engineered mutant evidence is separate from nutrient deficiency; no claim that R209C occurs in affected patients or that every receptor mechanism is excluded.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human CaSR expression system; engineered G-protein preparation
plain_language
The mutant experiments placed this Mg effect at the G-protein switch rather than simply at the receptor surface where calcium and magnesium bind.
primary_references
[quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
tissue_or_cell_type
HEK-293 membrane reconstitution
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 469–479
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered receptor and Galpha comparison in reconstituted signaling assays · source_derived_draft · unverified_draft
### galpha-r209c-removes-magnesium-dependence The low-Mg enhancement of CaSR-stimulated GTP analogue binding was lost with the reduced-Mg-sensitivity Galpha-i1 R209C mutant; changing receptor extracellular cation affinity did not remove it. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mutant experiments placed this Mg effect at the G-protein switch rather than simply at the receptor surface where calcium and magnesium bind. organism: Human CaSR expression system; engineered G-protein preparation tissue_or_cell_type: HEK-293 membrane reconstitution experimental_model: Engineered receptor and Galpha comparison in reconstituted signaling assays limitations: Engineered mutant evidence is separate from nutrient deficiency; no claim that R209C occurs in affected patients or that every receptor mechanism is excluded. cross_nutrient: magnesium -> CaSR/PTH -> calcium [quitterer-2001-magnesium-paradox] Paradoxical block of parathormone secretion is mediated by increased activity of G alpha subunits (2001). https://pubmed.ncbi.nlm.nih.gov/11102444/ DOI: 10.1074/jbc.M007727200
Complete structured claim and evidence
Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+.
Thiamine (vitamin B1) → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations.
limitations
Assay chemistry; no clinical response measured.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor.
primary_references
[onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
tissue_or_cell_type
Purified recombinant enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 481–491
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. · source_derived_draft · unverified_draft
### mg-tpk1-thiamine-to-thdp Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. limitations: Assay chemistry; no clinical response measured. 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. [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
Complete structured claim and evidence
Mg2+ in excess over ATP restored human TPK1 activity at low MgATP concentrations compared with a 1:1 total Mg:ATP ratio.
Mg2+ → Human thiamine pyrophosphokinase 1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations.
limitations
Total concentrations and speciation must be distinguished; no human Mg cutoff follows.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The balance between ATP-bound and available magnesium affects activation of B1.
primary_references
[onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
tissue_or_cell_type
Purified recombinant enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 493–503
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. · source_derived_draft · unverified_draft
### mg-tpk1-free-mg-restores-activity Mg2+ in excess over ATP restored human TPK1 activity at low MgATP concentrations compared with a 1:1 total Mg:ATP ratio. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The balance between ATP-bound and available magnesium affects activation of B1. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. limitations: Total concentrations and speciation must be distinguished; no human Mg cutoff follows. 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. [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
Complete structured claim and evidence
Mouse TPK structures place Mg2+ adjacent to thiamine/ThDP and coordinated by active-site aspartate residues.
Mg2+ → Mouse thiamine pyrophosphokinase 1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium.
limitations
Crystal packing may affect oligomer state; nucleotide analog density was not confidently assigned.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
Magnesium participates in the enzyme pocket that handles vitamin B1 phosphorylation.
primary_references
[liu-2011-tpk-structure] A new crystal form of mouse thiamin pyrophosphokinase (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3088427/
tissue_or_cell_type
Recombinant protein crystals
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 505–515
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium. · source_derived_draft · unverified_draft
### mg-mouse-tpk-metal-site Mouse TPK structures place Mg2+ adjacent to thiamine/ThDP and coordinated by active-site aspartate residues. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium participates in the enzyme pocket that handles vitamin B1 phosphorylation. organism: Mus musculus tissue_or_cell_type: Recombinant protein crystals experimental_model: Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium. limitations: Crystal packing may affect oligomer state; nucleotide analog density was not confidently assigned. 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. [liu-2011-tpk-structure] A new crystal form of mouse thiamin pyrophosphokinase (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3088427/
Complete structured claim and evidence
Recombinant mouse TPK1 showed an Mg optimum followed by inhibition as Mg was increased at fixed ATP.
Mg2+ → Mouse thiamine pyrophosphokinase 1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Purified recombinant mouse TPK1; forward and reverse reaction kinetics.
limitations
ATP concentration shifted the optimum; in vitro values are not intake targets.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
More magnesium did not continuously increase B1 activation in this assay.
primary_references
[sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
tissue_or_cell_type
Purified recombinant enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 517–527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant mouse TPK1; forward and reverse reaction kinetics. · source_derived_draft · unverified_draft
### mg-mouse-tpk-nonmonotonic Recombinant mouse TPK1 showed an Mg optimum followed by inhibition as Mg was increased at fixed ATP. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: More magnesium did not continuously increase B1 activation in this assay. organism: Mus musculus tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reaction kinetics. limitations: ATP concentration shifted the optimum; in vitro values are not intake targets. 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. [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
Accumulated ThDP inhibited the forward reaction of purified mouse TPK1.
Thiamine diphosphate → Mouse thiamine pyrophosphokinase 1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Purified recombinant mouse TPK1; forward and reverse reaction kinetics.
limitations
Product inhibition is a separate limit from Mg shortage.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mus musculus
plain_language
B1 activation has product feedback even when ATP and magnesium are supplied.
primary_references
[sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
tissue_or_cell_type
Purified recombinant enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 529–539
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant mouse TPK1; forward and reverse reaction kinetics. · source_derived_draft · unverified_draft
### mg-thdp-feedback-on-tpk Accumulated ThDP inhibited the forward reaction of purified mouse TPK1. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 activation has product feedback even when ATP and magnesium are supplied. organism: Mus musculus tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reaction kinetics. limitations: Product inhibition is a separate limit from Mg shortage. 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. [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
Sulfur-35-labeled ThDP binding was measured directly in human erythrocyte transketolase.
Thiamine diphosphate → Human transketolase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution.
limitations
Binding measurement alone does not establish tissue flux.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Tracer binding measures the vitamin-derived cofactor joining the enzyme.
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 541–551
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-radiolabeled-thdp-binding Sulfur-35-labeled ThDP binding was measured directly in human erythrocyte transketolase. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Tracer binding measures the vitamin-derived cofactor joining the enzyme. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. limitations: Binding measurement alone does not establish tissue flux. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5
Complete structured claim and evidence
Native transketolase purified from human erythrocytes contained magnesium.
Mg2+ → Human transketolase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution.
limitations
Metal content in one preparation does not establish exclusive metal specificity.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The isolated red-cell enzyme carried magnesium.
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 553–563
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-native-metal Native transketolase purified from human erythrocytes contained magnesium. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The isolated red-cell enzyme carried magnesium. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. limitations: Metal content in one preparation does not establish exclusive metal specificity. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5
Complete structured claim and evidence
Reconstituted erythrocyte transketolase activity ranked Co2+ < Mn2+ < Ca2+ < Mg2+ in the tested assay.
Calcium ion → Human transketolase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution.
limitations
Replacement in vitro does not establish physiological substitution during Mg deficiency.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Several divalent metals supported this B1-dependent enzyme; magnesium worked best here.
primary_references
[jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5
tissue_or_cell_type
Erythrocyte enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 565–575
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. · source_derived_draft · unverified_draft
### mg-tkt-other-divalent-cations Reconstituted erythrocyte transketolase activity ranked Co2+ < Mn2+ < Ca2+ < Mg2+ in the tested assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several divalent metals supported this B1-dependent enzyme; magnesium worked best here. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. limitations: Replacement in vitro does not establish physiological substitution during Mg deficiency. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5
Complete structured claim and evidence
Human erythrocyte apo-transketolase activation kinetics supported slow Mg-ThDP binding followed by slow isomerization.
Magnesium-thiamine diphosphate complex → Transketolase cofactor loading source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Human erythrocyte apo-transketolase reconstitution kinetics.
limitations
This is a kinetic interpretation; it differs from yeast reconstitution involving rate-limiting dimerization.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The cofactor-loading complex contains ThDP and magnesium, not ATP.
primary_references
[booth-1993-tkt] Reconstitution of holotransketolase is by a thiamin-diphosphate-magnesium complex (1993). https://pubmed.ncbi.nlm.nih.gov/8243472/ DOI: 10.1111/j.1432-1033.1993.tb18373.x
tissue_or_cell_type
Erythrocyte apoenzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 577–587
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte apo-transketolase reconstitution kinetics. · source_derived_draft · unverified_draft
### mg-tkt-loading-lag Human erythrocyte apo-transketolase activation kinetics supported slow Mg-ThDP binding followed by slow isomerization. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor-loading complex contains ThDP and magnesium, not ATP. organism: Homo sapiens tissue_or_cell_type: Erythrocyte apoenzyme experimental_model: Human erythrocyte apo-transketolase reconstitution kinetics. limitations: This is a kinetic interpretation; it differs from yeast reconstitution involving rate-limiting dimerization. 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. [booth-1993-tkt] Reconstitution of holotransketolase is by a thiamin-diphosphate-magnesium complex (1993). https://pubmed.ncbi.nlm.nih.gov/8243472/ DOI: 10.1111/j.1432-1033.1993.tb18373.x
Complete structured claim and evidence
In recombinant human TKT, Ca2+ coordinates the ThDP diphosphate and protein ligands at the active site.
Calcium ion → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Recombinant human TKT crystallography, kinetics and NMR.
limitations
Ca-supported structural preparation does not quantify native human tissue metal occupancy.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Calcium can anchor the B1-derived cofactor in active human transketolase.
primary_references
[mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955
tissue_or_cell_type
Recombinant TKT crystals
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 589–599
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TKT crystallography, kinetics and NMR. · source_derived_draft · unverified_draft
### mg-tkt-calcium-thdp-anchor In recombinant human TKT, Ca2+ coordinates the ThDP diphosphate and protein ligands at the active site. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium can anchor the B1-derived cofactor in active human transketolase. organism: Homo sapiens tissue_or_cell_type: Recombinant TKT crystals experimental_model: Recombinant human TKT crystallography, kinetics and NMR. limitations: Ca-supported structural preparation does not quantify native human tissue metal occupancy. 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. [mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955
Complete structured claim and evidence
Recombinant human TKT retained ThDP and Ca2+ strongly under cofactor-removal conditions used in the study.
Human transketolase → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Recombinant human TKT crystallography, kinetics and NMR.
limitations
Retention is preparation- and protocol-specific; this is not a measurement of in vivo Mg depletion.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The enzyme can retain loaded cofactors; free-metal changes need not immediately strip them away.
primary_references
[mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955
tissue_or_cell_type
Purified recombinant TKT
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 601–611
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TKT crystallography, kinetics and NMR. · source_derived_draft · unverified_draft
### mg-tkt-tight-cofactor-retention Recombinant human TKT retained ThDP and Ca2+ strongly under cofactor-removal conditions used in the study. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme can retain loaded cofactors; free-metal changes need not immediately strip them away. organism: Homo sapiens tissue_or_cell_type: Purified recombinant TKT experimental_model: Recombinant human TKT crystallography, kinetics and NMR. limitations: Retention is preparation- and protocol-specific; this is not a measurement of in vivo Mg depletion. 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. [mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955
Complete structured claim and evidence
Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site.
Mg2+ → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity.
limitations
Structure supports binding geometry; no magnesium-deficiency intervention was performed.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Magnesium helps position the B1-derived cofactor in the pyruvate-processing enzyme.
primary_references
[whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
tissue_or_cell_type
Recombinant mitochondrial enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 613–623
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. · source_derived_draft · unverified_draft
### mg-pdh-e1-thdp-anchor Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps position the B1-derived cofactor in the pyruvate-processing enzyme. organism: Homo sapiens tissue_or_cell_type: Recombinant mitochondrial enzyme experimental_model: Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. limitations: Structure supports binding geometry; no magnesium-deficiency intervention was performed. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
Complete structured claim and evidence
The alphaV138M E1 structure displaced ThDP and disrupted the canonical Mg coordination site.
Human pyruvate dehydrogenase E1 alphaV138M variant → Mg2+ source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity.
limitations
The variant also alters loop structure; Mg loss alone was not isolated as the cause.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
An altered protein can impair cofactor use despite cofactors being supplied.
primary_references
[whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
tissue_or_cell_type
Recombinant mitochondrial enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 625–635
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. · source_derived_draft · unverified_draft
### mg-pdh-variant-disrupts-coordination The alphaV138M E1 structure displaced ThDP and disrupted the canonical Mg coordination site. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An altered protein can impair cofactor use despite cofactors being supplied. organism: Homo sapiens tissue_or_cell_type: Recombinant mitochondrial enzyme experimental_model: Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. limitations: The variant also alters loop structure; Mg loss alone was not isolated as the cause. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
Complete structured claim and evidence
The human E1b coordinate model 1DTW contains two ThDP molecules and two Mg ions in its alpha2-beta2 assembly.
Human branched-chain ketoacid dehydrogenase E1 → Mg2+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Human E1b crystallography, deposited structure 1DTW.
limitations
Occupancy supports cofactor architecture; clinical Mg limitation was not tested.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The branched-chain ketoacid enzyme contains both vitamin B1-derived cofactor and magnesium.
primary_references
[aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2
structure_url
https://www.ncbi.nlm.nih.gov/Structure/pdb/1DTW
tissue_or_cell_type
Recombinant E1b crystal
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 637–648
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human E1b crystallography, deposited structure 1DTW. · source_derived_draft · unverified_draft
### mg-bckdh-e1-cofactor-occupancy The human E1b coordinate model 1DTW contains two ThDP molecules and two Mg ions in its alpha2-beta2 assembly. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The branched-chain ketoacid enzyme contains both vitamin B1-derived cofactor and magnesium. organism: Homo sapiens tissue_or_cell_type: Recombinant E1b crystal experimental_model: Human E1b crystallography, deposited structure 1DTW. limitations: Occupancy supports cofactor architecture; clinical Mg limitation was not tested. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. structure_url: https://www.ncbi.nlm.nih.gov/Structure/pdb/1DTW [aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2
Complete structured claim and evidence
Human E1b contains potassium sites, including one organizing a loop near the ThDP cofactor.
Potassium ion → Human branched-chain ketoacid dehydrogenase E1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Potassium and magnesium contribute distinct sites in a thiamine-dependent branched-chain ketoacid enzyme.
experimental_model
Human E1b crystallography, deposited structure 1DTW.
limitations
A structural potassium site is not a potassium-intake response experiment.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Potassium also helps shape this B1-dependent enzyme; the metal roles are distinct.
primary_references
[aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2
tissue_or_cell_type
Recombinant E1b crystal
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 650–660
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human E1b crystallography, deposited structure 1DTW. · source_derived_draft · unverified_draft
### mg-bckdh-potassium-site Human E1b contains potassium sites, including one organizing a loop near the ThDP cofactor. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium also helps shape this B1-dependent enzyme; the metal roles are distinct. organism: Homo sapiens tissue_or_cell_type: Recombinant E1b crystal experimental_model: Human E1b crystallography, deposited structure 1DTW. limitations: A structural potassium site is not a potassium-intake response experiment. cross_nutrient: Potassium and magnesium contribute distinct sites in a thiamine-dependent branched-chain ketoacid enzyme. [aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2
Complete structured claim and evidence
The human OGDH cryo-EM model 7WGR contains Mg and ThDP as well as a separate Ca-binding site.
Human 2-oxoglutarate dehydrogenase E1 → Mg2+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Human OGDH cryo-EM structure; deposited coordinate model 7WGR.
limitations
Structure does not establish a clinical Mg threshold or metal replacement equivalence.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The human alpha-ketoglutarate-processing enzyme has distinct cofactor and calcium-regulatory architecture.
primary_references
[zhong-2022-ogdh] Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM (2022). https://pubmed.ncbi.nlm.nih.gov/35272141/ DOI: 10.1016/j.bbrc.2022.02.093
structure_url
https://pdbj.org/mine/summary/7wgr
tissue_or_cell_type
Recombinant mitochondrial OGDH
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 662–673
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OGDH cryo-EM structure; deposited coordinate model 7WGR. · source_derived_draft · unverified_draft
### mg-ogdh-human-cofactor-structure The human OGDH cryo-EM model 7WGR contains Mg and ThDP as well as a separate Ca-binding site. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human alpha-ketoglutarate-processing enzyme has distinct cofactor and calcium-regulatory architecture. organism: Homo sapiens tissue_or_cell_type: Recombinant mitochondrial OGDH experimental_model: Human OGDH cryo-EM structure; deposited coordinate model 7WGR. limitations: Structure does not establish a clinical Mg threshold or metal replacement equivalence. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. structure_url: https://pdbj.org/mine/summary/7wgr [zhong-2022-ogdh] Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM (2022). https://pubmed.ncbi.nlm.nih.gov/35272141/ DOI: 10.1016/j.bbrc.2022.02.093
Complete structured claim and evidence
Mg increased purified pig-heart KGDHC activity only when ThDP was present in the assay.
Mg2+ → 2-Oxoglutarate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations.
limitations
Absence of added cofactor does not establish that all tightly bound cofactor was removed.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Magnesium and the B1-derived cofactor jointly supported maximal enzyme activity.
primary_references
[panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t
tissue_or_cell_type
Purified heart mitochondrial enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 675–685
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. · source_derived_draft · unverified_draft
### mg-ogdh-stimulation-requires-thdp Mg increased purified pig-heart KGDHC activity only when ThDP was present in the assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and the B1-derived cofactor jointly supported maximal enzyme activity. organism: Sus scrofa tissue_or_cell_type: Purified heart mitochondrial enzyme experimental_model: Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. limitations: Absence of added cofactor does not establish that all tightly bound cofactor was removed. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t
Complete structured claim and evidence
Ca and Mg stimulation of purified pig-heart KGDHC was additive over the tested lower free-ion ranges.
Calcium ion → 2-Oxoglutarate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium and magnesium effects on a thiamine-dependent enzyme were additive under specified assay conditions.
experimental_model
Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations.
limitations
Additivity depended on concentration; it does not imply Ca replaces Mg at the ThDP site.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Calcium regulation and magnesium support can act together in the enzyme preparation.
primary_references
[panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t
tissue_or_cell_type
Purified heart mitochondrial enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 687–697
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. · source_derived_draft · unverified_draft
### mg-ogdh-calcium-additivity Ca and Mg stimulation of purified pig-heart KGDHC was additive over the tested lower free-ion ranges. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium regulation and magnesium support can act together in the enzyme preparation. organism: Sus scrofa tissue_or_cell_type: Purified heart mitochondrial enzyme experimental_model: Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. limitations: Additivity depended on concentration; it does not imply Ca replaces Mg at the ThDP site. cross_nutrient: Calcium and magnesium effects on a thiamine-dependent enzyme were additive under specified assay conditions. [panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t
Complete structured claim and evidence
The 2000 experiments interpreted MgADP as a more potent OGDHC activator than free ADP.
Magnesium-ADP complex → 2-Oxoglutarate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments.
limitations
Speciation-based interpretation; later modeling offered independent Mg/ADP effects.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
The authors assigned enhanced activity to magnesium-bound ADP.
primary_references
[rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856
tissue_or_cell_type
Isolated heart enzyme; additional mitochondrial-extract source not resolved
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 699–709
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. · source_derived_draft · unverified_draft
### mg-ogdh-mgadp-interpretation The 2000 experiments interpreted MgADP as a more potent OGDHC activator than free ADP. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The authors assigned enhanced activity to magnesium-bound ADP. organism: Sus scrofa tissue_or_cell_type: Isolated heart enzyme; additional mitochondrial-extract source not resolved experimental_model: Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. limitations: Speciation-based interpretation; later modeling offered independent Mg/ADP effects. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856
Complete structured claim and evidence
The 2000 study attributed ATP inhibition to Mg chelation and an inhibitory effect of MgATP.
ATP → 2-Oxoglutarate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments.
limitations
The paper assigns more than one inhibitory mechanism; their in vivo contributions were not measured.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
ATP concentration can alter both free magnesium and nucleotide regulation of the enzyme.
primary_references
[rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856
tissue_or_cell_type
Isolated heart enzyme; additional mitochondrial-extract source not resolved
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 711–721
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. · source_derived_draft · unverified_draft
### mg-ogdh-atp-chelation-inhibition The 2000 study attributed ATP inhibition to Mg chelation and an inhibitory effect of MgATP. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP concentration can alter both free magnesium and nucleotide regulation of the enzyme. organism: Sus scrofa tissue_or_cell_type: Isolated heart enzyme; additional mitochondrial-extract source not resolved experimental_model: Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. limitations: The paper assigns more than one inhibitory mechanism; their in vivo contributions were not measured. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856
Complete structured claim and evidence
A 2011 kinetic reanalysis favored independent Mg and ADP effects rather than requiring MgADP as the activating species.
Mg2+ → 2-Oxoglutarate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets.
limitations
Computational inference, not a new binding measurement; more complex alternatives were not excluded.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mammalian datasets including Sus scrofa
plain_language
One model explains activation using two separate regulators.
primary_references
[qi-2011-ogdh] Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase (2011). https://link.springer.com/article/10.1186/1471-2091-12-53 DOI: 10.1186/1471-2091-12-53
tissue_or_cell_type
Published isolated-enzyme datasets
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 723–733
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets. · source_derived_draft · unverified_draft
### mg-ogdh-independent-adp-model A 2011 kinetic reanalysis favored independent Mg and ADP effects rather than requiring MgADP as the activating species. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: One model explains activation using two separate regulators. organism: Mammalian datasets including Sus scrofa tissue_or_cell_type: Published isolated-enzyme datasets experimental_model: Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets. limitations: Computational inference, not a new binding measurement; more complex alternatives were not excluded. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [qi-2011-ogdh] Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase (2011). https://link.springer.com/article/10.1186/1471-2091-12-53 DOI: 10.1186/1471-2091-12-53
Complete structured claim and evidence
In the 1974 report, blood transketolase recovered more slowly after thiamine in the hypomagnesemic patient than in two normomagnesemic patients.
Mg2+ → Blood transketolase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
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
Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment.
limitations
Three patients; blood transketolase is not direct brain flux.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Low serum magnesium accompanied a delayed blood-enzyme response to B1.
primary_references
[traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959
tissue_or_cell_type
Blood; acute Wernicke-Korsakoff patients
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 735–745
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. · source_derived_draft · unverified_draft
### mg-thiamine-delayed-blood-tkt In the 1974 report, blood transketolase recovered more slowly after thiamine in the hypomagnesemic patient than in two normomagnesemic patients. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low serum magnesium accompanied a delayed blood-enzyme response to B1. organism: Homo sapiens tissue_or_cell_type: Blood; acute Wernicke-Korsakoff patients experimental_model: Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. limitations: Three patients; blood transketolase is not direct brain flux. 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. [traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959
Complete structured claim and evidence
Correcting hypomagnesemia in the 1974 patient coincided with clearing of ophthalmoplegia.
Mg2+ → Ophthalmoplegia source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
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
Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment.
limitations
Uncontrolled within-patient sequence; no isolated enzyme mechanism established.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Eye-movement symptoms improved during magnesium correction after a delayed B1 response.
primary_references
[traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959
tissue_or_cell_type
Clinical neurological examination
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 747–757
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. · source_derived_draft · unverified_draft
### mg-thiamine-ocular-recovery Correcting hypomagnesemia in the 1974 patient coincided with clearing of ophthalmoplegia. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Eye-movement symptoms improved during magnesium correction after a delayed B1 response. organism: Homo sapiens tissue_or_cell_type: Clinical neurological examination experimental_model: Three acute Wernicke-Korsakoff patients: two normomagnesemic and one hypomagnesemic; serial blood transketolase and clinical assessment. limitations: Uncontrolled within-patient sequence; no isolated enzyme mechanism established. 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. [traviesa-1974-thiamine] Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff encephalopathy (1974). https://pubmed.ncbi.nlm.nih.gov/4420329/ DOI: 10.1136/jnnp.37.8.959
Complete structured claim and evidence
In the 2016 case, neurological symptoms resolved after intravenous Mg was added to ongoing thiamine for documented hypomagnesemia.
Mg2+ → Wernicke encephalopathy neurological symptoms source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
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
Single 34-year-old man with alcohol withdrawal and Wernicke encephalopathy during intravenous thiamine treatment.
limitations
Single case during alcohol withdrawal; no controlled comparison or tissue-cofactor measurement.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A patient improved with combined treatment after symptoms progressed during thiamine alone.
primary_references
[coughlan-2016-thiamine] Thiamine refractory Wernickes encephalopathy reversed with magnesium therapy (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5093844/ DOI: 10.1136/bcr-2016-218046
tissue_or_cell_type
Clinical neurological examination
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 759–769
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single 34-year-old man with alcohol withdrawal and Wernicke encephalopathy during intravenous thiamine treatment. · source_derived_draft · unverified_draft
### mg-thiamine-2016-neurologic-response In the 2016 case, neurological symptoms resolved after intravenous Mg was added to ongoing thiamine for documented hypomagnesemia. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A patient improved with combined treatment after symptoms progressed during thiamine alone. organism: Homo sapiens tissue_or_cell_type: Clinical neurological examination experimental_model: Single 34-year-old man with alcohol withdrawal and Wernicke encephalopathy during intravenous thiamine treatment. limitations: Single case during alcohol withdrawal; no controlled comparison or tissue-cofactor measurement. 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. [coughlan-2016-thiamine] Thiamine refractory Wernickes encephalopathy reversed with magnesium therapy (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC5093844/ DOI: 10.1136/bcr-2016-218046
Complete structured claim and evidence
Pre-steady-state pig-kidney pump experiments identified Mg as an essential activator of ATP-dependent phosphorylation.
Mg2+ → Sodium-potassium ATPase phosphorylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2.
limitations
Na-containing, K-free assay; not the full physiological transport cycle.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Magnesium enables the ATP-driven phosphate-transfer step of the sodium pump.
primary_references
[campos-1992-nka] Effects of magnesium and ATP on pre-steady-state phosphorylation kinetics of the Na+,K(+)-ATPase (1992). https://pubmed.ncbi.nlm.nih.gov/1314673/ DOI: 10.1016/0005-2736(92)90161-e
tissue_or_cell_type
Kidney enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 771–781
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2. · source_derived_draft · unverified_draft
### mg-nka-phosphorylation-requirement Pre-steady-state pig-kidney pump experiments identified Mg as an essential activator of ATP-dependent phosphorylation. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium enables the ATP-driven phosphate-transfer step of the sodium pump. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme experimental_model: Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2. limitations: Na-containing, K-free assay; not the full physiological transport cycle. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [campos-1992-nka] Effects of magnesium and ATP on pre-steady-state phosphorylation kinetics of the Na+,K(+)-ATPase (1992). https://pubmed.ncbi.nlm.nih.gov/1314673/ DOI: 10.1016/0005-2736(92)90161-e
Complete structured claim and evidence
The 1992 best-fit model allowed free ATP or MgATP to bind before productive Mg-dependent phosphorylation.
ATP → Sodium-potassium ATPase complexes source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2.
limitations
Kinetic model, not proof of Mg-free catalysis; binding and phosphate transfer are distinct.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
A requirement for magnesium does not prove that only a preformed MgATP molecule can bind.
primary_references
[campos-1992-nka] Effects of magnesium and ATP on pre-steady-state phosphorylation kinetics of the Na+,K(+)-ATPase (1992). https://pubmed.ncbi.nlm.nih.gov/1314673/ DOI: 10.1016/0005-2736(92)90161-e
tissue_or_cell_type
Kidney enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 783–793
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2. · source_derived_draft · unverified_draft
### mg-nka-atp-binding-order-boundary The 1992 best-fit model allowed free ATP or MgATP to bind before productive Mg-dependent phosphorylation. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A requirement for magnesium does not prove that only a preformed MgATP molecule can bind. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme experimental_model: Pig-kidney Na/K-ATPase rapid-mixing phosphorylation; Na-containing, K-free medium; varied ATP and MgCl2. limitations: Kinetic model, not proof of Mg-free catalysis; binding and phosphate transfer are distinct. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [campos-1992-nka] Effects of magnesium and ATP on pre-steady-state phosphorylation kinetics of the Na+,K(+)-ATPase (1992). https://pubmed.ncbi.nlm.nih.gov/1314673/ DOI: 10.1016/0005-2736(92)90161-e
Complete structured claim and evidence
Shark-pump kinetic fits assigned E1-ATP Mg affinity mainly to ATP coordination, after accounting for free ATP competition.
Magnesium-ATP complex → Sodium-potassium ATPase phosphorylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Shark rectal-gland pump membrane fragments; stopped-flow RH421 fluorescence under Na-rich conditions.
limitations
Conclusion concerns E1-ATP; other pump conformations or Mg sites can behave differently.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Shark
plain_language
The ATP-associated magnesium supports phosphorylation; free ATP can compete for that magnesium.
primary_references
[pilotelle-2009-nka] Mechanism of Mg2+ binding in the Na+,K+-ATPase (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2711396/ DOI: 10.1016/j.bpj.2009.01.042
tissue_or_cell_type
Rectal-gland enzyme membrane fragments
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 795–805
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Shark rectal-gland pump membrane fragments; stopped-flow RH421 fluorescence under Na-rich conditions. · source_derived_draft · unverified_draft
### mg-nka-atp-dominates-mg-binding Shark-pump kinetic fits assigned E1-ATP Mg affinity mainly to ATP coordination, after accounting for free ATP competition. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The ATP-associated magnesium supports phosphorylation; free ATP can compete for that magnesium. organism: Shark tissue_or_cell_type: Rectal-gland enzyme membrane fragments experimental_model: Shark rectal-gland pump membrane fragments; stopped-flow RH421 fluorescence under Na-rich conditions. limitations: Conclusion concerns E1-ATP; other pump conformations or Mg sites can behave differently. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [pilotelle-2009-nka] Mechanism of Mg2+ binding in the Na+,K+-ATPase (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2711396/ DOI: 10.1016/j.bpj.2009.01.042
Complete structured claim and evidence
Adding KCl after ATP phosphorylation accelerated dephosphorylation of pig-kidney Na/K-ATPase.
Potassium ion → Sodium-potassium ATPase dephosphorylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing.
limitations
Stopped-flow assay; no dietary or magnesium-depletion intervention.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Potassium promotes the phosphate-removal part of the pump cycle.
primary_references
[kane-1998-nka] Dephosphorylation kinetics of pig kidney Na+,K+-ATPase (1998). https://pubmed.ncbi.nlm.nih.gov/9521778/ DOI: 10.1021/bi972813e
tissue_or_cell_type
Kidney enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 807–817
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing. · source_derived_draft · unverified_draft
### mg-nka-potassium-dephosphorylation Adding KCl after ATP phosphorylation accelerated dephosphorylation of pig-kidney Na/K-ATPase. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium promotes the phosphate-removal part of the pump cycle. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme experimental_model: Pig-kidney enzyme stopped-flow RH421 fluorescence; sequential ATP then KCl mixing. limitations: Stopped-flow assay; no dietary or magnesium-depletion intervention. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [kane-1998-nka] Dephosphorylation kinetics of pig kidney Na+,K+-ATPase (1998). https://pubmed.ncbi.nlm.nih.gov/9521778/ DOI: 10.1021/bi972813e
Complete structured claim and evidence
In Mg-loaded human red-cell ghosts, ouabain-sensitive hydrolysis of one ATP accompanied loss of about three sodium ions.
ATP → Sodium-pump-mediated sodium efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP.
limitations
Measured stoichiometry applies to specified ionic conditions; no Mg titration was performed.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
ATP turnover was directly linked to outward sodium pumping in a magnesium-containing preparation.
primary_references
[garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297
tissue_or_cell_type
Resealed erythrocyte ghosts
transport_direction
Sodium: intracellular ghost compartment to external medium.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 819–830
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. · source_derived_draft · unverified_draft
### mg-nka-isotope-atp-sodium-coupling In Mg-loaded human red-cell ghosts, ouabain-sensitive hydrolysis of one ATP accompanied loss of about three sodium ions. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP turnover was directly linked to outward sodium pumping in a magnesium-containing preparation. organism: Homo sapiens tissue_or_cell_type: Resealed erythrocyte ghosts experimental_model: Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. limitations: Measured stoichiometry applies to specified ionic conditions; no Mg titration was performed. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. transport_direction: Sodium: intracellular ghost compartment to external medium. [garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297
Complete structured claim and evidence
Sodium-24 and potassium-42 experiments demonstrated ouabain-sensitive sodium efflux and potassium influx in human red cells.
Sodium-potassium ATPase complexes → Sodium-pump-mediated potassium influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP.
limitations
This experiment found unequal fluxes but did not itself measure an exact 3:2 ratio.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The pump moves the two nutrient ions in opposite directions.
primary_references
[garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297
tissue_or_cell_type
Erythrocytes
transport_direction
Sodium outward; potassium inward.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 832–843
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. · source_derived_draft · unverified_draft
### mg-nka-isotope-opposed-flux Sodium-24 and potassium-42 experiments demonstrated ouabain-sensitive sodium efflux and potassium influx in human red cells. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pump moves the two nutrient ions in opposite directions. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Human red cells and resealed ghosts; ATP/Mg loading, ouabain, sodium-24, potassium-42 and gamma-phosphorus-32 ATP. limitations: This experiment found unequal fluxes but did not itself measure an exact 3:2 ratio. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. transport_direction: Sodium outward; potassium inward. [garrahan-1967-nka] The stoicheiometry of the sodium pump (1967). https://doi.org/10.1113/jphysiol.1967.sp008297 DOI: 10.1113/jphysiol.1967.sp008297
Complete structured claim and evidence
Mg occupied cation transport site II in the ouabain-bound E2P pig-kidney pump structure.
Mg2+ → Sodium-potassium ATPase complexes source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Phosphorylated pig-kidney Na/K-ATPase-ouabain complex crystallography.
limitations
Drug-stabilized inhibited state; it does not demonstrate physiological Mg transport.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Magnesium can occupy a membrane ion site distinct from the ATP-associated catalytic site.
primary_references
[laursen-2013-nka] Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site (2013). https://pubmed.ncbi.nlm.nih.gov/23776223/ DOI: 10.1073/pnas.1222308110
tissue_or_cell_type
Kidney enzyme crystals
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 845–855
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylated pig-kidney Na/K-ATPase-ouabain complex crystallography. · source_derived_draft · unverified_draft
### mg-nka-distinct-transport-site Mg occupied cation transport site II in the ouabain-bound E2P pig-kidney pump structure. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium can occupy a membrane ion site distinct from the ATP-associated catalytic site. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme crystals experimental_model: Phosphorylated pig-kidney Na/K-ATPase-ouabain complex crystallography. limitations: Drug-stabilized inhibited state; it does not demonstrate physiological Mg transport. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [laursen-2013-nka] Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site (2013). https://pubmed.ncbi.nlm.nih.gov/23776223/ DOI: 10.1073/pnas.1222308110
Complete structured claim and evidence
Free Mg reduced apparent sodium affinity in pig-kidney pump sodium-22 occlusion experiments.
Mg2+ → Sodium occlusion by sodium-potassium ATPase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration.
experimental_model
Partially purified pig-kidney pump; sodium-22 occlusion, EGCg quench-flow, ATP/Mg manipulations.
limitations
Equilibrium and Na-ATPase conditions; full Na/K exchange and systemic Mg deficiency were not tested.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Sus scrofa
plain_language
Magnesium can oppose sodium binding as well as support ATP chemistry.
primary_references
[faraj-2023-nka] Measurements of Na+-occluded intermediates during the catalytic cycle of the Na+/K+-ATPase provide novel insights into the mechanism of Na+ transport (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC9860123/ DOI: 10.1016/j.jbc.2022.102811
tissue_or_cell_type
Kidney enzyme membrane preparation
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 857–867
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified pig-kidney pump; sodium-22 occlusion, EGCg quench-flow, ATP/Mg manipulations. · source_derived_draft · unverified_draft
### mg-nka-free-mg-sodium-occlusion Free Mg reduced apparent sodium affinity in pig-kidney pump sodium-22 occlusion experiments. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium can oppose sodium binding as well as support ATP chemistry. organism: Sus scrofa tissue_or_cell_type: Kidney enzyme membrane preparation experimental_model: Partially purified pig-kidney pump; sodium-22 occlusion, EGCg quench-flow, ATP/Mg manipulations. limitations: Equilibrium and Na-ATPase conditions; full Na/K exchange and systemic Mg deficiency were not tested. cross_nutrient: Magnesium-dependent ATP chemistry is coupled to sodium and potassium handling by the pump; serum magnesium is not the enzyme-site concentration. [faraj-2023-nka] Measurements of Na+-occluded intermediates during the catalytic cycle of the Na+/K+-ATPase provide novel insights into the mechanism of Na+ transport (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC9860123/ DOI: 10.1016/j.jbc.2022.102811
Complete structured claim and evidence
Recombinant TRPM6 expression generated Mg2+-permeable currents, supporting its participation in apical epithelial Mg entry.
TRPM6 → Cellular magnesium influx source_derived_draftungraded
Experimental context and source evidence
evidence-system
Recombinant channel recordings and tissue localization
experimental_model
Recombinant channel recordings and tissue localization
limitations
Expression-system currents do not establish the stoichiometry of native channels; TRPM7 can contribute.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human protein; mouse tissues
plain_language
TRPM6 is part of the route by which magnesium crosses an epithelial cell membrane.
primary_references
[voets-2004-trpm6] TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. (2004). https://pubmed.ncbi.nlm.nih.gov/14576148/ DOI: 10.1074/jbc.M311201200
tissue
HEK expression cells; intestine and distal renal tubule
tissue_or_cell_type
HEK expression cells; intestine and distal renal tubule
transport_direction
Extracellular or luminal compartment toward cytosol.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 869–881
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant channel recordings and tissue localization · source_derived_draft · unverified_draft
### trpm6-mg-entry Recombinant TRPM6 expression generated Mg2+-permeable currents, supporting its participation in apical epithelial Mg entry. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: TRPM6 is part of the route by which magnesium crosses an epithelial cell membrane. organism: Human protein; mouse tissues tissue_or_cell_type: HEK expression cells; intestine and distal renal tubule experimental_model: Recombinant channel recordings and tissue localization limitations: Expression-system currents do not establish the stoichiometry of native channels; TRPM7 can contribute. transport_direction: Extracellular or luminal compartment toward cytosol. evidence-system: Recombinant channel recordings and tissue localization tissue: HEK expression cells; intestine and distal renal tubule [voets-2004-trpm6] TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. (2004). https://pubmed.ncbi.nlm.nih.gov/14576148/ DOI: 10.1074/jbc.M311201200
Complete structured claim and evidence
TRPM6 coassembled with TRPM7 to form functional surface channel complexes in the tested expression systems.
TRPM6 → TRPM7 source_derived_draftungraded
Experimental context and source evidence
evidence-system
HEK293 and Xenopus heterologous coexpression
experimental_model
HEK293 and Xenopus heterologous coexpression
limitations
TRPM6 isoforms and cellular background affect results; not proof every native complex has identical composition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human proteins; human-derived and Xenopus cells
plain_language
A TRPM7 partner enabled TRPM6-containing channels to reach and function at the cell surface.
primary_references
[chubanov-2004-trpm6-trpm7] Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. (2004). https://pubmed.ncbi.nlm.nih.gov/14976260/ DOI: 10.1073/pnas.0305252101
tissue
Expression systems
tissue_or_cell_type
Expression systems
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 883–894
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HEK293 and Xenopus heterologous coexpression · source_derived_draft · unverified_draft
### trpm6-trpm7-coassembly TRPM6 coassembled with TRPM7 to form functional surface channel complexes in the tested expression systems. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A TRPM7 partner enabled TRPM6-containing channels to reach and function at the cell surface. organism: Human proteins; human-derived and Xenopus cells tissue_or_cell_type: Expression systems experimental_model: HEK293 and Xenopus heterologous coexpression limitations: TRPM6 isoforms and cellular background affect results; not proof every native complex has identical composition. evidence-system: HEK293 and Xenopus heterologous coexpression tissue: Expression systems [chubanov-2004-trpm6-trpm7] Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. (2004). https://pubmed.ncbi.nlm.nih.gov/14976260/ DOI: 10.1073/pnas.0305252101
Complete structured claim and evidence
TRPM6 S141L disrupted oligomeric assembly and functional TRPM6/TRPM7 complex formation.
TRPM6 S141L → TRPM6/TRPM7 heteromeric channel complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Mutant coexpression and channel assembly assays
experimental_model
Mutant coexpression and channel assembly assays
limitations
A particular variant mechanism; not all TRPM6 variants act by defective trafficking.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human proteins
plain_language
This disease-associated substitution damages assembly of the magnesium-entry machinery.
primary_references
[chubanov-2004-trpm6-trpm7] Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. (2004). https://pubmed.ncbi.nlm.nih.gov/14976260/ DOI: 10.1073/pnas.0305252101
tissue
HEK293 and Xenopus expression systems
tissue_or_cell_type
HEK293 and Xenopus expression systems
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 896–907
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutant coexpression and channel assembly assays · source_derived_draft · unverified_draft
### trpm6-s141l-assembly-defect TRPM6 S141L disrupted oligomeric assembly and functional TRPM6/TRPM7 complex formation. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This disease-associated substitution damages assembly of the magnesium-entry machinery. organism: Human proteins tissue_or_cell_type: HEK293 and Xenopus expression systems experimental_model: Mutant coexpression and channel assembly assays limitations: A particular variant mechanism; not all TRPM6 variants act by defective trafficking. evidence-system: Mutant coexpression and channel assembly assays tissue: HEK293 and Xenopus expression systems [chubanov-2004-trpm6-trpm7] Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia. (2004). https://pubmed.ncbi.nlm.nih.gov/14976260/ DOI: 10.1073/pnas.0305252101
Complete structured claim and evidence
Pathogenic biallelic TRPM6 variants were identified in families with hypomagnesemia and secondary hypocalcemia.
TRPM6 loss-of-function genotype → Serum magnesium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Calcium concentration also fell in the inherited Mg-handling disorder; this record does not specify the downstream endocrine mechanism.
evidence-system
Familial positional genetics
experimental_model
Familial positional genetics
limitations
Mapping alone does not apportion intestinal versus renal contributions or prove every downstream symptom is Mg-only.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
Inherited failure of magnesium handling produced a recognizable low-magnesium disorder.
primary_references
[schlingmann-2002-trpm6] Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. (2002). https://pubmed.ncbi.nlm.nih.gov/12032568/ DOI: 10.1038/ng889
tissue
Intestine and kidney implicated; serum phenotype
tissue_or_cell_type
Intestine and kidney implicated; serum phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 909–921
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Familial positional genetics · source_derived_draft · unverified_draft
### human-trpm6-loss-low-magnesium Pathogenic biallelic TRPM6 variants were identified in families with hypomagnesemia and secondary hypocalcemia. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inherited failure of magnesium handling produced a recognizable low-magnesium disorder. organism: Human tissue_or_cell_type: Intestine and kidney implicated; serum phenotype experimental_model: Familial positional genetics limitations: Mapping alone does not apportion intestinal versus renal contributions or prove every downstream symptom is Mg-only. cross_nutrient: Calcium concentration also fell in the inherited Mg-handling disorder; this record does not specify the downstream endocrine mechanism. evidence-system: Familial positional genetics tissue: Intestine and kidney implicated; serum phenotype [schlingmann-2002-trpm6] Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. (2002). https://pubmed.ncbi.nlm.nih.gov/12032568/ DOI: 10.1038/ng889
Complete structured claim and evidence
Intestine-restricted Trpm6 deletion reduced serum and bone magnesium in the tested adult mice.
Intestine-specific Trpm6-null mouse genotype → Serum magnesium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Villin1-Cre conditional deletion; six-month-old male mice
experimental_model
Villin1-Cre conditional deletion; six-month-old male mice
limitations
Colon expression was detected; the outcome does not quantify the contribution of each human intestinal segment.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Removing intestinal TRPM6 impaired systemic magnesium supply despite intact kidneys.
primary_references
[chubanov-2016-trpm6] Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival (2016). https://elifesciences.org/articles/20914 DOI: 10.7554/eLife.20914
tissue
Intestinal epithelium; serum and bone
tissue_or_cell_type
Intestinal epithelium; serum and bone
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 923–934
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Villin1-Cre conditional deletion; six-month-old male mice · source_derived_draft · unverified_draft
### intestinal-trpm6-loss-low-magnesium Intestine-restricted Trpm6 deletion reduced serum and bone magnesium in the tested adult mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing intestinal TRPM6 impaired systemic magnesium supply despite intact kidneys. organism: Mouse tissue_or_cell_type: Intestinal epithelium; serum and bone experimental_model: Villin1-Cre conditional deletion; six-month-old male mice limitations: Colon expression was detected; the outcome does not quantify the contribution of each human intestinal segment. evidence-system: Villin1-Cre conditional deletion; six-month-old male mice tissue: Intestinal epithelium; serum and bone [chubanov-2016-trpm6] Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival (2016). https://elifesciences.org/articles/20914 DOI: 10.7554/eLife.20914
Complete structured claim and evidence
Kidney-restricted Trpm6 deletion did not lower serum Mg or raise urinary Mg in the tested mice.
Kidney-specific Trpm6-null mouse genotype → Serum magnesium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Ksp-Cre conditional deletion; six-month-old male mice
experimental_model
Ksp-Cre conditional deletion; six-month-old male mice
limitations
Bone Mg was slightly reduced; this is not proof renal TRPM6 is dispensable under every diet or in humans.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
These mice maintained circulating magnesium after kidney-specific TRPM6 loss.
primary_references
[chubanov-2016-trpm6] Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival (2016). https://elifesciences.org/articles/20914 DOI: 10.7554/eLife.20914
tissue
Kidney; serum and urine
tissue_or_cell_type
Kidney; serum and urine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 936–947
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ksp-Cre conditional deletion; six-month-old male mice · source_derived_draft · unverified_draft
### renal-trpm6-loss-serum-preserved Kidney-restricted Trpm6 deletion did not lower serum Mg or raise urinary Mg in the tested mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: These mice maintained circulating magnesium after kidney-specific TRPM6 loss. organism: Mouse tissue_or_cell_type: Kidney; serum and urine experimental_model: Ksp-Cre conditional deletion; six-month-old male mice limitations: Bone Mg was slightly reduced; this is not proof renal TRPM6 is dispensable under every diet or in humans. evidence-system: Ksp-Cre conditional deletion; six-month-old male mice tissue: Kidney; serum and urine [chubanov-2016-trpm6] Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival (2016). https://elifesciences.org/articles/20914 DOI: 10.7554/eLife.20914
Complete structured claim and evidence
TRPM7-deficient DT40 cells became magnesium depleted.
TRPM7 loss-of-function genotype → Cellular magnesium content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Targeted gene disruption and Mg measurements in DT40 cells
experimental_model
Targeted gene disruption and Mg measurements in DT40 cells
limitations
Cell-line dependence does not establish universal necessity in every mammalian cell.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Chicken
plain_language
Loss of this entry channel reduced the cells magnesium supply.
primary_references
[schmitz-2003-trpm7] Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7 (2003). https://pubmed.ncbi.nlm.nih.gov/12887921/ DOI: 10.1016/S0092-8674(03)00556-7
tissue
B-cell line
tissue_or_cell_type
B-cell line
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 949–960
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted gene disruption and Mg measurements in DT40 cells · source_derived_draft · unverified_draft
### trpm7-loss-cellular-magnesium TRPM7-deficient DT40 cells became magnesium depleted. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of this entry channel reduced the cells magnesium supply. organism: Chicken tissue_or_cell_type: B-cell line experimental_model: Targeted gene disruption and Mg measurements in DT40 cells limitations: Cell-line dependence does not establish universal necessity in every mammalian cell. evidence-system: Targeted gene disruption and Mg measurements in DT40 cells tissue: B-cell line [schmitz-2003-trpm7] Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7 (2003). https://pubmed.ncbi.nlm.nih.gov/12887921/ DOI: 10.1016/S0092-8674(03)00556-7
Complete structured claim and evidence
Increasing extracellular Mg restored proliferation and viability of TRPM7-deficient DT40 cells.
Mg2+ → Cell proliferation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Extracellular magnesium supplementation after TRPM7 disruption
experimental_model
Extracellular magnesium supplementation after TRPM7 disruption
limitations
Culture rescue is not a clinical dose recommendation or evidence all TRPM7 functions are Mg-dependent.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Chicken
plain_language
Additional magnesium bypassed enough of the transport defect to restore cultured-cell growth.
primary_references
[schmitz-2003-trpm7] Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7 (2003). https://pubmed.ncbi.nlm.nih.gov/12887921/ DOI: 10.1016/S0092-8674(03)00556-7
tissue
DT40 B-cell culture
tissue_or_cell_type
DT40 B-cell culture
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 962–973
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Extracellular magnesium supplementation after TRPM7 disruption · source_derived_draft · unverified_draft
### magnesium-rescues-trpm7-cell-proliferation Increasing extracellular Mg restored proliferation and viability of TRPM7-deficient DT40 cells. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Additional magnesium bypassed enough of the transport defect to restore cultured-cell growth. organism: Chicken tissue_or_cell_type: DT40 B-cell culture experimental_model: Extracellular magnesium supplementation after TRPM7 disruption limitations: Culture rescue is not a clinical dose recommendation or evidence all TRPM7 functions are Mg-dependent. evidence-system: Extracellular magnesium supplementation after TRPM7 disruption tissue: DT40 B-cell culture [schmitz-2003-trpm7] Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7 (2003). https://pubmed.ncbi.nlm.nih.gov/12887921/ DOI: 10.1016/S0092-8674(03)00556-7
Complete structured claim and evidence
Intestinal Trpm7 deletion lowered magnesium availability in early postnatal mice.
Intestine-specific Trpm7-null mouse genotype → Serum magnesium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Villin1-Cre conditional deletion and mineral phenotyping
experimental_model
Villin1-Cre conditional deletion and mineral phenotyping
limitations
Early developmental model; not a test of dietary Mg restriction.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Suckling mice required intestinal TRPM7 to maintain their magnesium supply.
primary_references
[mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
tissue
Intestinal enterocytes; serum
tissue_or_cell_type
Intestinal enterocytes; serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 975–986
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Villin1-Cre conditional deletion and mineral phenotyping · source_derived_draft · unverified_draft
### intestinal-trpm7-loss-magnesium Intestinal Trpm7 deletion lowered magnesium availability in early postnatal mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suckling mice required intestinal TRPM7 to maintain their magnesium supply. organism: Mouse tissue_or_cell_type: Intestinal enterocytes; serum experimental_model: Villin1-Cre conditional deletion and mineral phenotyping limitations: Early developmental model; not a test of dietary Mg restriction. evidence-system: Villin1-Cre conditional deletion and mineral phenotyping tissue: Intestinal enterocytes; serum [mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
Complete structured claim and evidence
Intestinal Trpm7 deletion reduced serum and bone calcium in suckling mice.
Intestine-specific Trpm7-null mouse genotype → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
TRPM7 is shared machinery for magnesium and calcium handling in this developmental model; causal Mg-to-Ca nutritional dependence was not isolated.
evidence-system
Conditional knockout; postnatal mineral phenotyping
experimental_model
Conditional knockout; postnatal mineral phenotyping
limitations
Shared channel loss; does not prove low Mg intake causes calcium malabsorption.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
The same epithelial channel machinery supports calcium as well as magnesium supply.
primary_references
[mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
tissue
Intestine; serum and bone
tissue_or_cell_type
Intestine; serum and bone
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 988–1000
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional knockout; postnatal mineral phenotyping · source_derived_draft · unverified_draft
### intestinal-trpm7-loss-calcium Intestinal Trpm7 deletion reduced serum and bone calcium in suckling mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same epithelial channel machinery supports calcium as well as magnesium supply. organism: Mouse tissue_or_cell_type: Intestine; serum and bone experimental_model: Conditional knockout; postnatal mineral phenotyping limitations: Shared channel loss; does not prove low Mg intake causes calcium malabsorption. cross_nutrient: TRPM7 is shared machinery for magnesium and calcium handling in this developmental model; causal Mg-to-Ca nutritional dependence was not isolated. evidence-system: Conditional knockout; postnatal mineral phenotyping tissue: Intestine; serum and bone [mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
Complete structured claim and evidence
Intestinal Trpm7 deletion reduced circulating zinc in early postnatal mice.
Intestine-specific Trpm7-null mouse genotype → Serum zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Shared intestinal TRPM7 machinery links zinc and magnesium availability; Mg deficiency as the cause of Zn deficiency was not demonstrated.
evidence-system
Conditional intestinal knockout and mineral phenotyping
experimental_model
Conditional intestinal knockout and mineral phenotyping
limitations
Not evidence that magnesium supplementation universally increases zinc absorption.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
A single epithelial machinery defect depleted zinc along with magnesium.
primary_references
[mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
tissue
Intestine; serum
tissue_or_cell_type
Intestine; serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1002–1014
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal knockout and mineral phenotyping · source_derived_draft · unverified_draft
### intestinal-trpm7-loss-zinc Intestinal Trpm7 deletion reduced circulating zinc in early postnatal mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A single epithelial machinery defect depleted zinc along with magnesium. organism: Mouse tissue_or_cell_type: Intestine; serum experimental_model: Conditional intestinal knockout and mineral phenotyping limitations: Not evidence that magnesium supplementation universally increases zinc absorption. cross_nutrient: Shared intestinal TRPM7 machinery links zinc and magnesium availability; Mg deficiency as the cause of Zn deficiency was not demonstrated. evidence-system: Conditional intestinal knockout and mineral phenotyping tissue: Intestine; serum [mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
Complete structured claim and evidence
EGF increased TRPM6-associated current in transfected HEK293 cells through EGFR-dependent signaling.
Epidermal growth factor → TRPM6-associated channel current source_derived_draftungraded
Experimental context and source evidence
evidence-system
EGF exposure and receptor-blocking patch-clamp experiments
experimental_model
EGF exposure and receptor-blocking patch-clamp experiments
exposure
10 nM EGF for 30 minutes in the main stimulation experiment; a concentration-response series and EGFR blockade were also tested.
limitations
Channel-current regulation was directly tested in expression cells, not native human DCT recordings.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human proteins and human-derived cells
plain_language
The growth factor EGF signals through its receptor to increase magnesium-channel activity.
primary_references
[groenestege-2007-egf] Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia (2007). https://www.jci.org/articles/view/31680 DOI: 10.1172/JCI31680
tissue
HEK293 cells
tissue_or_cell_type
HEK293 cells
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1016–1028
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · EGF exposure and receptor-blocking patch-clamp experiments · source_derived_draft · unverified_draft
### egf-increases-trpm6-current EGF increased TRPM6-associated current in transfected HEK293 cells through EGFR-dependent signaling. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The growth factor EGF signals through its receptor to increase magnesium-channel activity. organism: Human proteins and human-derived cells tissue_or_cell_type: HEK293 cells experimental_model: EGF exposure and receptor-blocking patch-clamp experiments limitations: Channel-current regulation was directly tested in expression cells, not native human DCT recordings. exposure: 10 nM EGF for 30 minutes in the main stimulation experiment; a concentration-response series and EGFR blockade were also tested. evidence-system: EGF exposure and receptor-blocking patch-clamp experiments tissue: HEK293 cells [groenestege-2007-egf] Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia (2007). https://www.jci.org/articles/view/31680 DOI: 10.1172/JCI31680
Complete structured claim and evidence
Pro-EGF P1070L impaired basolateral delivery of TRPM6-stimulating EGF activity in polarized MDCK experiments.
Pro-EGF P1070L → Basolateral EGF release source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Polarized MDCK conditioned-medium assays applied to TRPM6-expressing HEK293 cells
experimental_model
Polarized MDCK conditioned-medium assays applied to TRPM6-expressing HEK293 cells
limitations
Functional conditioned-medium evidence; no quantitative human DCT ligand measurement.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human protein; canine and human-derived cells
plain_language
The mutation sends insufficient active signal to the epithelial side containing the relevant receptor.
primary_references
[groenestege-2007-egf] Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia (2007). https://www.jci.org/articles/view/31680 DOI: 10.1172/JCI31680
tissue
Polarized epithelial model
tissue_or_cell_type
Polarized epithelial model
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1030–1041
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized MDCK conditioned-medium assays applied to TRPM6-expressing HEK293 cells · source_derived_draft · unverified_draft
### pro-egf-variant-loses-basolateral-signal Pro-EGF P1070L impaired basolateral delivery of TRPM6-stimulating EGF activity in polarized MDCK experiments. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mutation sends insufficient active signal to the epithelial side containing the relevant receptor. organism: Human protein; canine and human-derived cells tissue_or_cell_type: Polarized epithelial model experimental_model: Polarized MDCK conditioned-medium assays applied to TRPM6-expressing HEK293 cells limitations: Functional conditioned-medium evidence; no quantitative human DCT ligand measurement. evidence-system: Polarized MDCK conditioned-medium assays applied to TRPM6-expressing HEK293 cells tissue: Polarized epithelial model [groenestege-2007-egf] Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia (2007). https://www.jci.org/articles/view/31680 DOI: 10.1172/JCI31680
Complete structured claim and evidence
Two homozygous EGF P1070L sisters had low serum magnesium with inappropriately sustained urinary Mg loss.
Pro-EGF P1070L → Urinary magnesium excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Human pedigree and serum/urine phenotyping
experimental_model
Human pedigree and serum/urine phenotyping
limitations
Small kindred; cellular sorting experiments support the explanation rather than directly measuring the entire cascade in vivo.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
The inherited EGF defect was linked to failure of the kidneys to conserve magnesium.
primary_references
[groenestege-2007-egf] Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia (2007). https://www.jci.org/articles/view/31680 DOI: 10.1172/JCI31680
tissue
Kidney; serum and urine
tissue_or_cell_type
Kidney; serum and urine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1043–1054
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human pedigree and serum/urine phenotyping · source_derived_draft · unverified_draft
### egf-variant-human-magnesium-wasting Two homozygous EGF P1070L sisters had low serum magnesium with inappropriately sustained urinary Mg loss. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inherited EGF defect was linked to failure of the kidneys to conserve magnesium. organism: Human tissue_or_cell_type: Kidney; serum and urine experimental_model: Human pedigree and serum/urine phenotyping limitations: Small kindred; cellular sorting experiments support the explanation rather than directly measuring the entire cascade in vivo. evidence-system: Human pedigree and serum/urine phenotyping tissue: Kidney; serum and urine [groenestege-2007-egf] Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia (2007). https://www.jci.org/articles/view/31680 DOI: 10.1172/JCI31680
Complete structured claim and evidence
Human CLDN16 mutations were linked to renal magnesium wasting in the positional-cloning study.
CLDN16 loss-of-function genotype → Urinary magnesium excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Human familial positional genetics and kidney localization
experimental_model
Human familial positional genetics and kidney localization
limitations
Establishes essential machinery; does not by itself identify a Mg-selective pore.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
A renal tight-junction protein is necessary for the kidney to retain magnesium normally.
primary_references
[simon-1999-cldn16] Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption (1999). https://pubmed.ncbi.nlm.nih.gov/10390358/ DOI: 10.1126/science.285.5424.103
tissue
Renal thick ascending limb
tissue_or_cell_type
Renal thick ascending limb
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1056–1067
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human familial positional genetics and kidney localization · source_derived_draft · unverified_draft
### human-cldn16-magnesium-wasting Human CLDN16 mutations were linked to renal magnesium wasting in the positional-cloning study. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A renal tight-junction protein is necessary for the kidney to retain magnesium normally. organism: Human tissue_or_cell_type: Renal thick ascending limb experimental_model: Human familial positional genetics and kidney localization limitations: Establishes essential machinery; does not by itself identify a Mg-selective pore. evidence-system: Human familial positional genetics and kidney localization tissue: Renal thick ascending limb [simon-1999-cldn16] Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption (1999). https://pubmed.ncbi.nlm.nih.gov/10390358/ DOI: 10.1126/science.285.5424.103
Complete structured claim and evidence
Pathogenic CLDN19 variants were identified in families with renal magnesium loss and hypomagnesemia.
CLDN19 loss-of-function genotype → Urinary magnesium excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
The disorder also includes abnormal calcium handling; shared renal machinery is implicated rather than competition for dietary absorption.
curation_notes
Existing catalog claim fb9278a2-5be5-5e4b-92f3-e02f00f3cfc7 covers the same families with urinary-calcium-excretion endpoint. This magnesium endpoint is deliberately separate.
evidence-system
Human family genetics with trafficking and assembly support
experimental_model
Human family genetics with trafficking and assembly support
limitations
Associated retinal abnormalities are not assigned solely to low Mg.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
Claudin-19 failure can make the kidneys lose magnesium.
primary_references
[konrad-2006-cldn19] Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement (2006). https://pubmed.ncbi.nlm.nih.gov/17033971/ DOI: 10.1086/508617
tissue
Renal tubules
tissue_or_cell_type
Renal tubules
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1069–1082
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics with trafficking and assembly support · source_derived_draft · unverified_draft
### human-cldn19-magnesium-wasting Pathogenic CLDN19 variants were identified in families with renal magnesium loss and hypomagnesemia. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Claudin-19 failure can make the kidneys lose magnesium. organism: Human tissue_or_cell_type: Renal tubules experimental_model: Human family genetics with trafficking and assembly support limitations: Associated retinal abnormalities are not assigned solely to low Mg. cross_nutrient: The disorder also includes abnormal calcium handling; shared renal machinery is implicated rather than competition for dietary absorption. curation_notes: Existing catalog claim fb9278a2-5be5-5e4b-92f3-e02f00f3cfc7 covers the same families with urinary-calcium-excretion endpoint. This magnesium endpoint is deliberately separate. evidence-system: Human family genetics with trafficking and assembly support tissue: Renal tubules [konrad-2006-cldn19] Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement (2006). https://pubmed.ncbi.nlm.nih.gov/17033971/ DOI: 10.1086/508617
Complete structured claim and evidence
In the cited RNAi mice, depletion of either claudin-16 or claudin-19 displaced the other from TAL tight junctions.
Claudin-16/claudin-19 complex → TAL claudin junctional localization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Reciprocal claudin RNAi mouse models and immunolocalization
experimental_model
Reciprocal claudin RNAi mouse models and immunolocalization
limitations
RNAi-model result; do not universalize junctional interdependence across all knockout backgrounds or human tissue.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
The two proteins depended on each other for normal junction placement in these knockdown mice.
primary_references
[hou-2009-claudin-assembly] Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2741254/ DOI: 10.1073/pnas.0907724106
tissue
Renal thick ascending limb
tissue_or_cell_type
Renal thick ascending limb
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1084–1095
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reciprocal claudin RNAi mouse models and immunolocalization · source_derived_draft · unverified_draft
### claudin-depletion-displaces-partner In the cited RNAi mice, depletion of either claudin-16 or claudin-19 displaced the other from TAL tight junctions. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two proteins depended on each other for normal junction placement in these knockdown mice. organism: Mouse tissue_or_cell_type: Renal thick ascending limb experimental_model: Reciprocal claudin RNAi mouse models and immunolocalization limitations: RNAi-model result; do not universalize junctional interdependence across all knockout backgrounds or human tissue. evidence-system: Reciprocal claudin RNAi mouse models and immunolocalization tissue: Renal thick ascending limb [hou-2009-claudin-assembly] Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium (2009). https://pmc.ncbi.nlm.nih.gov/articles/PMC2741254/ DOI: 10.1073/pnas.0907724106
Complete structured claim and evidence
Claudin-16 RNAi reduced paracellular cation selectivity in isolated mouse thick ascending limbs.
Claudin-16 RNAi mouse genotype → TAL paracellular cation selectivity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
TAL electrical selectivity participates in magnesium and calcium conservation; no dietary synergy is implied.
evidence-system
Renal RNAi and isolated TAL electrophysiology
experimental_model
Renal RNAi and isolated TAL electrophysiology
limitations
Selectivity evidence is not proof claudin-16 alone forms a specifically magnesium-selective pore.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
The junction lost part of its preference for positively charged ions, changing the conditions that support mineral recovery.
primary_references
[hou-2007-cldn16] Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. (2007). https://pubmed.ncbi.nlm.nih.gov/17442678/ DOI: 10.1074/jbc.M700632200
tissue
Renal thick ascending limb
tissue_or_cell_type
Renal thick ascending limb
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1097–1109
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Renal RNAi and isolated TAL electrophysiology · source_derived_draft · unverified_draft
### cldn16-depletion-selectivity Claudin-16 RNAi reduced paracellular cation selectivity in isolated mouse thick ascending limbs. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The junction lost part of its preference for positively charged ions, changing the conditions that support mineral recovery. organism: Mouse tissue_or_cell_type: Renal thick ascending limb experimental_model: Renal RNAi and isolated TAL electrophysiology limitations: Selectivity evidence is not proof claudin-16 alone forms a specifically magnesium-selective pore. cross_nutrient: TAL electrical selectivity participates in magnesium and calcium conservation; no dietary synergy is implied. evidence-system: Renal RNAi and isolated TAL electrophysiology tissue: Renal thick ascending limb [hou-2007-cldn16] Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. (2007). https://pubmed.ncbi.nlm.nih.gov/17442678/ DOI: 10.1074/jbc.M700632200
Complete structured claim and evidence
Claudin-16 RNAi mice developed renal magnesium wasting.
Claudin-16 RNAi mouse genotype → Urinary magnesium excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Calcium wasting accompanied magnesium loss after shared tight-junction impairment.
evidence-system
Transgenic Cldn16 RNAi with renal mineral phenotyping
experimental_model
Transgenic Cldn16 RNAi with renal mineral phenotyping
limitations
This organismal endpoint accompanies selectivity changes; the experiment does not isolate every intervening transport step.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Reducing this tight-junction component made the kidneys lose magnesium.
primary_references
[hou-2007-cldn16] Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. (2007). https://pubmed.ncbi.nlm.nih.gov/17442678/ DOI: 10.1074/jbc.M700632200
tissue
Kidney; urine
tissue_or_cell_type
Kidney; urine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1111–1123
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transgenic Cldn16 RNAi with renal mineral phenotyping · source_derived_draft · unverified_draft
### cldn16-rnai-magnesium-loss Claudin-16 RNAi mice developed renal magnesium wasting. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing this tight-junction component made the kidneys lose magnesium. organism: Mouse tissue_or_cell_type: Kidney; urine experimental_model: Transgenic Cldn16 RNAi with renal mineral phenotyping limitations: This organismal endpoint accompanies selectivity changes; the experiment does not isolate every intervening transport step. cross_nutrient: Calcium wasting accompanied magnesium loss after shared tight-junction impairment. evidence-system: Transgenic Cldn16 RNAi with renal mineral phenotyping tissue: Kidney; urine [hou-2007-cldn16] Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. (2007). https://pubmed.ncbi.nlm.nih.gov/17442678/ DOI: 10.1074/jbc.M700632200
Complete structured claim and evidence
CNNM2 variants in the reported families associated with hypomagnesemia, seizures and developmental impairment.
Pathogenic CNNM2 variants → CNNM2-associated neurodevelopmental phenotype source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Five unrelated families plus functional and zebrafish evidence
experimental_model
Five unrelated families plus functional and zebrafish evidence
limitations
Neurological features persisted despite supplementation; do not equate the full genetic phenotype with reversible dietary Mg deficiency.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
This inherited disorder includes neurological abnormalities alongside low magnesium.
primary_references
[arjona-2014-cnnm2] CNNM2 Mutations Cause Impaired Brain Development and Seizures in Patients with Hypomagnesemia (2014). https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004267 DOI: 10.1371/journal.pgen.1004267
tissue
Kidney and nervous system
tissue_or_cell_type
Kidney and nervous system
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1125–1136
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five unrelated families plus functional and zebrafish evidence · source_derived_draft · unverified_draft
### cnnm2-variants-neurodevelopment CNNM2 variants in the reported families associated with hypomagnesemia, seizures and developmental impairment. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inherited disorder includes neurological abnormalities alongside low magnesium. organism: Human tissue_or_cell_type: Kidney and nervous system experimental_model: Five unrelated families plus functional and zebrafish evidence limitations: Neurological features persisted despite supplementation; do not equate the full genetic phenotype with reversible dietary Mg deficiency. evidence-system: Five unrelated families plus functional and zebrafish evidence tissue: Kidney and nervous system [arjona-2014-cnnm2] CNNM2 Mutations Cause Impaired Brain Development and Seizures in Patients with Hypomagnesemia (2014). https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004267 DOI: 10.1371/journal.pgen.1004267
Complete structured claim and evidence
Neither CNNM2 isoform 1 nor isoform 2 produced detectable extra Mg influx or efflux in the reported HEK293 assays.
CNNM2 → Cellular magnesium influx source_derived_draftungraded
Experimental context and source evidence
evidence-system
Inducible expression, electrophysiology and mag-fura-2 measurements
experimental_model
Inducible expression, electrophysiology and mag-fura-2 measurements
limitations
A negative expression-system result cannot exclude context-dependent transport or interaction with other machinery.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human proteins and human-derived cells
plain_language
In this experiment, expressing CNNM2 did not behave like adding an independent magnesium transporter.
primary_references
[sponder-2016-cnnm2] Human CNNM2 is not a Mg2+ transporter per se (2016). https://pubmed.ncbi.nlm.nih.gov/27068403/ DOI: 10.1007/s00424-016-1816-7
tissue
HEK293 culture
tissue_or_cell_type
HEK293 culture
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1138–1149
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible expression, electrophysiology and mag-fura-2 measurements · source_derived_draft · unverified_draft
### cnnm2-isoforms-no-extra-mg-flux Neither CNNM2 isoform 1 nor isoform 2 produced detectable extra Mg influx or efflux in the reported HEK293 assays. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this experiment, expressing CNNM2 did not behave like adding an independent magnesium transporter. organism: Human proteins and human-derived cells tissue_or_cell_type: HEK293 culture experimental_model: Inducible expression, electrophysiology and mag-fura-2 measurements limitations: A negative expression-system result cannot exclude context-dependent transport or interaction with other machinery. evidence-system: Inducible expression, electrophysiology and mag-fura-2 measurements tissue: HEK293 culture [sponder-2016-cnnm2] Human CNNM2 is not a Mg2+ transporter per se (2016). https://pubmed.ncbi.nlm.nih.gov/27068403/ DOI: 10.1007/s00424-016-1816-7
Complete structured claim and evidence
CNNM2 coexpression increased TRPM7-dependent zinc influx, and the TRPM7 E1047K pore mutant prevented this increase.
CNNM2 → Cellular zinc influx source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
A protein associated with Mg homeostasis regulates a Zn-permeable channel in culture; nutritional co-dependence was not tested.
evidence-system
Coexpression, TRPM7 knockout and pore-inactivation tests
experimental_model
Coexpression, TRPM7 knockout and pore-inactivation tests
limitations
Zinc is a divalent-flux reporter here; this does not establish CNNM2 as a magnesium pore or dietary Mg-to-Zn dependence.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human proteins and human-derived cells
plain_language
CNNM2 can regulate entry through a separate channel whose pore carries the ion.
primary_references
[bai-2021-cnnm-trpm7] CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8726484/ DOI: 10.1371/journal.pbio.3001496
tissue
HEK293-family cells; supporting HAP1 cells
tissue_or_cell_type
HEK293-family cells; supporting HAP1 cells
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1151–1163
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Coexpression, TRPM7 knockout and pore-inactivation tests · source_derived_draft · unverified_draft
### cnnm2-stimulates-trpm7-zinc-influx CNNM2 coexpression increased TRPM7-dependent zinc influx, and the TRPM7 E1047K pore mutant prevented this increase. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: CNNM2 can regulate entry through a separate channel whose pore carries the ion. organism: Human proteins and human-derived cells tissue_or_cell_type: HEK293-family cells; supporting HAP1 cells experimental_model: Coexpression, TRPM7 knockout and pore-inactivation tests limitations: Zinc is a divalent-flux reporter here; this does not establish CNNM2 as a magnesium pore or dietary Mg-to-Zn dependence. cross_nutrient: A protein associated with Mg homeostasis regulates a Zn-permeable channel in culture; nutritional co-dependence was not tested. evidence-system: Coexpression, TRPM7 knockout and pore-inactivation tests tissue: HEK293-family cells; supporting HAP1 cells [bai-2021-cnnm-trpm7] CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC8726484/ DOI: 10.1371/journal.pbio.3001496
Complete structured claim and evidence
Human SLC41A1-associated Mg efflux in HEK293 cells fell sharply when extracellular sodium was replaced in the Kolisek assay.
SLC41A1 → Cellular magnesium efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Sodium availability affected measured magnesium export in this assay; coupling is contested.
evidence-system
Human construct overexpression; mag-fura-2; extracellular Na replacement
experimental_model
Human construct overexpression; mag-fura-2; extracellular Na replacement
limitations
Indirect free-ion assay and overexpression; conflicts with sodium-independent isotope flux in a different construct/protocol.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human protein and human-derived cells
plain_language
This experiment supported sodium-coupled export of magnesium.
primary_references
[kolisek-2012-slc41a1] Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger (2012). https://pubmed.ncbi.nlm.nih.gov/22031603/ DOI: 10.1152/ajpcell.00289.2011
tissue
HEK293 cells
tissue_or_cell_type
HEK293 cells
transport_direction
Mg2+ from cytosol toward extracellular solution.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1165–1178
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human construct overexpression; mag-fura-2; extracellular Na replacement · source_derived_draft · unverified_draft
### slc41a1-sodium-dependent-efflux Human SLC41A1-associated Mg efflux in HEK293 cells fell sharply when extracellular sodium was replaced in the Kolisek assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This experiment supported sodium-coupled export of magnesium. organism: Human protein and human-derived cells tissue_or_cell_type: HEK293 cells experimental_model: Human construct overexpression; mag-fura-2; extracellular Na replacement limitations: Indirect free-ion assay and overexpression; conflicts with sodium-independent isotope flux in a different construct/protocol. cross_nutrient: Sodium availability affected measured magnesium export in this assay; coupling is contested. transport_direction: Mg2+ from cytosol toward extracellular solution. evidence-system: Human construct overexpression; mag-fura-2; extracellular Na replacement tissue: HEK293 cells [kolisek-2012-slc41a1] Human gene SLC41A1 encodes for the Na+/Mg2+ exchanger (2012). https://pubmed.ncbi.nlm.nih.gov/22031603/ DOI: 10.1152/ajpcell.00289.2011
Complete structured claim and evidence
Mouse SLC41A1 expressed in HEK293 cells supported Mg extrusion without extracellular sodium in the Arjona isotope assay.
SLC41A1 → Cellular magnesium efflux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
This assay challenges obligatory sodium dependence of SLC41A1-associated magnesium extrusion.
evidence-system
Mouse SLC41A1 construct; stable-isotope 25Mg measurements
experimental_model
Mouse SLC41A1 construct; stable-isotope 25Mg measurements
limitations
Different ortholog, loading and readout from the sodium-dependent report; physiological coupling remains unresolved.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse protein; human-derived cells
plain_language
A different experiment found magnesium export that did not require sodium.
primary_references
[arjona-2019-slc41a1] SLC41A1 is essential for magnesium homeostasis in vivo (2019). https://pubmed.ncbi.nlm.nih.gov/30417250/ DOI: 10.1007/s00424-018-2234-9
tissue
HEK293 cells
tissue_or_cell_type
HEK293 cells
transport_direction
Mg2+ from cytosol toward extracellular solution.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1180–1193
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse SLC41A1 construct; stable-isotope 25Mg measurements · source_derived_draft · unverified_draft
### slc41a1-sodium-independent-efflux Mouse SLC41A1 expressed in HEK293 cells supported Mg extrusion without extracellular sodium in the Arjona isotope assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different experiment found magnesium export that did not require sodium. organism: Mouse protein; human-derived cells tissue_or_cell_type: HEK293 cells experimental_model: Mouse SLC41A1 construct; stable-isotope 25Mg measurements limitations: Different ortholog, loading and readout from the sodium-dependent report; physiological coupling remains unresolved. cross_nutrient: This assay challenges obligatory sodium dependence of SLC41A1-associated magnesium extrusion. transport_direction: Mg2+ from cytosol toward extracellular solution. evidence-system: Mouse SLC41A1 construct; stable-isotope 25Mg measurements tissue: HEK293 cells [arjona-2019-slc41a1] SLC41A1 is essential for magnesium homeostasis in vivo (2019). https://pubmed.ncbi.nlm.nih.gov/30417250/ DOI: 10.1007/s00424-018-2234-9
Complete structured claim and evidence
Slc41a1-null mice maintained serum and urinary Mg similarly to littermates under standard and Mg-restricted diets.
Slc41a1-null mouse genotype → Serum magnesium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Constitutive knockout with dietary Mg restriction challenge
experimental_model
Constitutive knockout with dietary Mg restriction challenge
limitations
Does not prove absence of all cell-specific functions; zebrafish and overexpression findings have different scope.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Deleting SLC41A1 did not make these mice uniquely unable to maintain magnesium balance.
primary_references
[ilenwabor-2022-slc41a1] SLC41A1 knockout mice display normal magnesium homeostasis (2022). https://pubmed.ncbi.nlm.nih.gov/36049064/ DOI: 10.1152/ajprenal.00101.2022
tissue
Kidney; serum and urine
tissue_or_cell_type
Kidney; serum and urine
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1195–1206
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Constitutive knockout with dietary Mg restriction challenge · source_derived_draft · unverified_draft
### slc41a1-null-mouse-magnesium-preserved Slc41a1-null mice maintained serum and urinary Mg similarly to littermates under standard and Mg-restricted diets. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deleting SLC41A1 did not make these mice uniquely unable to maintain magnesium balance. organism: Mouse tissue_or_cell_type: Kidney; serum and urine experimental_model: Constitutive knockout with dietary Mg restriction challenge limitations: Does not prove absence of all cell-specific functions; zebrafish and overexpression findings have different scope. evidence-system: Constitutive knockout with dietary Mg restriction challenge tissue: Kidney; serum and urine [ilenwabor-2022-slc41a1] SLC41A1 knockout mice display normal magnesium homeostasis (2022). https://pubmed.ncbi.nlm.nih.gov/36049064/ DOI: 10.1152/ajprenal.00101.2022
Complete structured claim and evidence
Cryo-EM resolved human MRS2 as a homopentamer surrounding a central pore.
Human mitochondrial MRS2 → Human MRS2 homopentamer source_derived_draftungraded
Experimental context and source evidence
evidence-system
Purified recombinant human MRS2 cryo-EM
experimental_model
Purified recombinant human MRS2 cryo-EM
limitations
Structure alone does not establish every gating transition or physiological selectivity.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human protein
plain_language
Five MRS2 subunits form the mitochondrial ion-conduction architecture.
primary_references
[human-mrs2-2023-permeation] Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel (2023). https://www.nature.com/articles/s41467-023-40516-2 DOI: 10.1038/s41467-023-40516-2
tissue
Protein purified from HEK293F expression
tissue_or_cell_type
Protein purified from HEK293F expression
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1208–1219
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human MRS2 cryo-EM · source_derived_draft · unverified_draft
### human-mrs2-pentamer Cryo-EM resolved human MRS2 as a homopentamer surrounding a central pore. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Five MRS2 subunits form the mitochondrial ion-conduction architecture. organism: Human protein tissue_or_cell_type: Protein purified from HEK293F expression experimental_model: Purified recombinant human MRS2 cryo-EM limitations: Structure alone does not establish every gating transition or physiological selectivity. evidence-system: Purified recombinant human MRS2 cryo-EM tissue: Protein purified from HEK293F expression [human-mrs2-2023-permeation] Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel (2023). https://www.nature.com/articles/s41467-023-40516-2 DOI: 10.1038/s41467-023-40516-2
Complete structured claim and evidence
MRS2 overexpression increased Mg uptake into HEK293F-derived mitochondria.
Human mitochondrial MRS2 → Mitochondrial magnesium uptake source_derived_draftungraded
Experimental context and source evidence
evidence-system
Isolated mitochondria from MRS2-overexpressing cells
experimental_model
Isolated mitochondria from MRS2-overexpressing cells
limitations
Uptake assay is not an intervention on dietary magnesium.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
More MRS2 increased magnesium entry into the mitochondrial compartment.
primary_references
[human-mrs2-2023-permeation] Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel (2023). https://www.nature.com/articles/s41467-023-40516-2 DOI: 10.1038/s41467-023-40516-2
tissue
HEK293F-derived mitochondria
tissue_or_cell_type
HEK293F-derived mitochondria
transport_direction
Intermembrane-space side toward matrix.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1221–1233
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated mitochondria from MRS2-overexpressing cells · source_derived_draft · unverified_draft
### human-mrs2-magnesium-uptake MRS2 overexpression increased Mg uptake into HEK293F-derived mitochondria. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: More MRS2 increased magnesium entry into the mitochondrial compartment. organism: Human tissue_or_cell_type: HEK293F-derived mitochondria experimental_model: Isolated mitochondria from MRS2-overexpressing cells limitations: Uptake assay is not an intervention on dietary magnesium. transport_direction: Intermembrane-space side toward matrix. evidence-system: Isolated mitochondria from MRS2-overexpressing cells tissue: HEK293F-derived mitochondria [human-mrs2-2023-permeation] Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel (2023). https://www.nature.com/articles/s41467-023-40516-2 DOI: 10.1038/s41467-023-40516-2
Complete structured claim and evidence
Dissipating membrane potential reduced Mg uptake in the human MRS2 mitochondrial assay.
Inner mitochondrial membrane potential → Mitochondrial magnesium uptake source_derived_draftungraded
Experimental context and source evidence
evidence-system
FCCP or valinomycin exposure of isolated mitochondria
experimental_model
FCCP or valinomycin exposure of isolated mitochondria
limitations
Pharmacological potential collapse can affect other mitochondrial properties; does not imply direct ATP hydrolysis by MRS2.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
The inner membrane electrical gradient helps drive magnesium into mitochondria.
primary_references
[human-mrs2-2023-permeation] Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel (2023). https://www.nature.com/articles/s41467-023-40516-2 DOI: 10.1038/s41467-023-40516-2
tissue
HEK293F-derived mitochondria
tissue_or_cell_type
HEK293F-derived mitochondria
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1235–1246
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · FCCP or valinomycin exposure of isolated mitochondria · source_derived_draft · unverified_draft
### mitochondrial-potential-supports-mrs2-uptake Dissipating membrane potential reduced Mg uptake in the human MRS2 mitochondrial assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inner membrane electrical gradient helps drive magnesium into mitochondria. organism: Human tissue_or_cell_type: HEK293F-derived mitochondria experimental_model: FCCP or valinomycin exposure of isolated mitochondria limitations: Pharmacological potential collapse can affect other mitochondrial properties; does not imply direct ATP hydrolysis by MRS2. evidence-system: FCCP or valinomycin exposure of isolated mitochondria tissue: HEK293F-derived mitochondria [human-mrs2-2023-permeation] Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel (2023). https://www.nature.com/articles/s41467-023-40516-2 DOI: 10.1038/s41467-023-40516-2
Complete structured claim and evidence
Yeast mrs2 deletion abolished the rapid mitochondrial Mg influx component while slow residual accumulation remained.
Yeast mrs2 deletion genotype → Mitochondrial magnesium uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Isolated mitochondria; mrs2 deletion and fluorescent free-Mg readout
experimental_model
Isolated mitochondria; mrs2 deletion and fluorescent free-Mg readout
limitations
Do not merge the yeast protein with human MRS2 or claim complete absence of every influx pathway.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Saccharomyces cerevisiae
plain_language
The yeast channel is required for rapid magnesium entry into mitochondria.
primary_references
[kolisek-2003-mrs2] Mrs2p is an essential component of the major electrophoretic Mg2+ influx system in mitochondria (2003). https://pmc.ncbi.nlm.nih.gov/articles/PMC151051/ DOI: 10.1093/emboj/cdg122
tissue
Mitochondria
tissue_or_cell_type
Mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1248–1259
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated mitochondria; mrs2 deletion and fluorescent free-Mg readout · source_derived_draft · unverified_draft
### yeast-mrs2-deletion-rapid-influx Yeast mrs2 deletion abolished the rapid mitochondrial Mg influx component while slow residual accumulation remained. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The yeast channel is required for rapid magnesium entry into mitochondria. organism: Saccharomyces cerevisiae tissue_or_cell_type: Mitochondria experimental_model: Isolated mitochondria; mrs2 deletion and fluorescent free-Mg readout limitations: Do not merge the yeast protein with human MRS2 or claim complete absence of every influx pathway. evidence-system: Isolated mitochondria; mrs2 deletion and fluorescent free-Mg readout tissue: Mitochondria [kolisek-2003-mrs2] Mrs2p is an essential component of the major electrophoretic Mg2+ influx system in mitochondria (2003). https://pmc.ncbi.nlm.nih.gov/articles/PMC151051/ DOI: 10.1093/emboj/cdg122
Complete structured claim and evidence
Extracellular Mg caused voltage-dependent block of NMDA-type currents in cultured mouse neurons, stronger at hyperpolarized potentials.
Mg2+ → NMDA receptor-mediated current source_derived_draftungraded
Experimental context and source evidence
evidence-system
Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes
experimental_model
Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes
limitations
Native channel subunits were not resolved; no nutritional intake or clinical outcome was tested.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Magnesium restrains this excitatory current in a way that depends on membrane voltage.
primary_references
[nowak-1984-nmda] Magnesium gates glutamate-activated channels in mouse central neurones (1984). https://pubmed.ncbi.nlm.nih.gov/6320006/ DOI: 10.1038/307462a0
tissue
Cultured central neurons
tissue_or_cell_type
Cultured central neurons
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1261–1272
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes · source_derived_draft · unverified_draft
### magnesium-voltage-dependent-nmda-block Extracellular Mg caused voltage-dependent block of NMDA-type currents in cultured mouse neurons, stronger at hyperpolarized potentials. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium restrains this excitatory current in a way that depends on membrane voltage. organism: Mouse tissue_or_cell_type: Cultured central neurons experimental_model: Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes limitations: Native channel subunits were not resolved; no nutritional intake or clinical outcome was tested. evidence-system: Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes tissue: Cultured central neurons [nowak-1984-nmda] Magnesium gates glutamate-activated channels in mouse central neurones (1984). https://pubmed.ncbi.nlm.nih.gov/6320006/ DOI: 10.1038/307462a0
Complete structured claim and evidence
Removing extracellular Mg reduced voltage dependence and relieved inward NMDA current block in cultured mouse spinal neurons.
Mg2+ → NMDA receptor-mediated current source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence-system
Voltage clamp; extracellular Mg withdrawal
experimental_model
Voltage clamp; extracellular Mg withdrawal
exposure
Withdrawal of approximately 1 mM extracellular Mg from neuronal bathing fluid; not a dietary or serum exposure.
limitations
Experimental bath depletion is distinct from low intake, serum hypomagnesemia or measured brain Mg depletion.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Loss of extracellular magnesium removes a brake on excitatory current in this preparation.
primary_references
[mayer-1984-nmda] Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones (1984). https://pubmed.ncbi.nlm.nih.gov/6325946/ DOI: 10.1038/309261a0
tissue
Cultured spinal cord neurons
tissue_or_cell_type
Cultured spinal cord neurons
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1274–1286
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Voltage clamp; extracellular Mg withdrawal · source_derived_draft · unverified_draft
### low-bath-magnesium-relieves-nmda-block Removing extracellular Mg reduced voltage dependence and relieved inward NMDA current block in cultured mouse spinal neurons. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of extracellular magnesium removes a brake on excitatory current in this preparation. organism: Mouse tissue_or_cell_type: Cultured spinal cord neurons experimental_model: Voltage clamp; extracellular Mg withdrawal limitations: Experimental bath depletion is distinct from low intake, serum hypomagnesemia or measured brain Mg depletion. exposure: Withdrawal of approximately 1 mM extracellular Mg from neuronal bathing fluid; not a dietary or serum exposure. evidence-system: Voltage clamp; extracellular Mg withdrawal tissue: Cultured spinal cord neurons [mayer-1984-nmda] Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones (1984). https://pubmed.ncbi.nlm.nih.gov/6325946/ DOI: 10.1038/309261a0
Complete structured claim and evidence
Increasing intracellular free Mg reduced Ca2+ and Ba2+ currents through recombinant CaV1.2.
Mg2+ → CaV1.2-mediated ionic current source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg availability directly modulated Ca-channel function in an expression assay, not intestinal calcium absorption.
evidence-system
Whole-cell recordings with intracellular free-Mg control; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits
experimental_model
Whole-cell recordings with intracellular free-Mg control; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits
exposure
Calculated intracellular free Mg was varied over 0.1-7.2 mM, with a 0.8 mM control; pipette MgATP was held at 5 mM. Ca2+ or Ba2+ served as the permeant ion in separate recordings.
limitations
Free Mg was experimentally controlled; no dietary intake, serum threshold or cardiac event was measured.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rabbit cardiac CaV1.2 protein expressed in human-derived tsA-201 cells
plain_language
Free magnesium inside the cell can restrain current through a calcium-entry channel.
primary_references
[brunet-2005-cav12] Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC2266622/ DOI: 10.1085/jgp.200509333
tissue
tsA-201 cells
tissue_or_cell_type
tsA-201 cells
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1288–1301
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell recordings with intracellular free-Mg control; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits · source_derived_draft · unverified_draft
### intracellular-magnesium-reduces-cav12-current Increasing intracellular free Mg reduced Ca2+ and Ba2+ currents through recombinant CaV1.2. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Free magnesium inside the cell can restrain current through a calcium-entry channel. organism: Rabbit cardiac CaV1.2 protein expressed in human-derived tsA-201 cells tissue_or_cell_type: tsA-201 cells experimental_model: Whole-cell recordings with intracellular free-Mg control; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits limitations: Free Mg was experimentally controlled; no dietary intake, serum threshold or cardiac event was measured. cross_nutrient: Mg availability directly modulated Ca-channel function in an expression assay, not intestinal calcium absorption. exposure: Calculated intracellular free Mg was varied over 0.1-7.2 mM, with a 0.8 mM control; pipette MgATP was held at 5 mM. Ca2+ or Ba2+ served as the permeant ion in separate recordings. evidence-system: Whole-cell recordings with intracellular free-Mg control; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits tissue: tsA-201 cells [brunet-2005-cav12] Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC2266622/ DOI: 10.1085/jgp.200509333
Complete structured claim and evidence
CaV1.2 EF-hand substitutions shifted Mg inhibition, with D1546K eliminating sensitivity across the tested range.
CaV1.2 EF-hand mutants tested by Brunet et al. → CaV1.2-mediated ionic current source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
The regulatory protein site connects intracellular magnesium with calcium-channel current.
evidence-system
EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits
experimental_model
EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits
exposure
Calculated intracellular free Mg was varied over 0.1-7.2 mM, with a 0.8 mM control; pipette MgATP was held at 5 mM. Ca2+ or Ba2+ served as the permeant ion in separate recordings.
limitations
Supports an EF-hand-associated regulatory mechanism; not direct structural observation of bound Mg.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rabbit cardiac CaV1.2 protein expressed in human-derived tsA-201 cells
plain_language
Changing the channel regulatory site changed its response to intracellular magnesium.
primary_references
[brunet-2005-cav12] Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC2266622/ DOI: 10.1085/jgp.200509333
tissue
tsA-201 cells
tissue_or_cell_type
tsA-201 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1303–1316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits · source_derived_draft · unverified_draft
### cav12-ef-hand-magnesium-sensitivity CaV1.2 EF-hand substitutions shifted Mg inhibition, with D1546K eliminating sensitivity across the tested range. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the channel regulatory site changed its response to intracellular magnesium. organism: Rabbit cardiac CaV1.2 protein expressed in human-derived tsA-201 cells tissue_or_cell_type: tsA-201 cells experimental_model: EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits limitations: Supports an EF-hand-associated regulatory mechanism; not direct structural observation of bound Mg. cross_nutrient: The regulatory protein site connects intracellular magnesium with calcium-channel current. exposure: Calculated intracellular free Mg was varied over 0.1-7.2 mM, with a 0.8 mM control; pipette MgATP was held at 5 mM. Ca2+ or Ba2+ served as the permeant ion in separate recordings. evidence-system: EF-hand mutagenesis and patch clamp; rabbit cardiac CaV1.2 with beta1b and alpha2delta auxiliary subunits tissue: tsA-201 cells [brunet-2005-cav12] Modulation of CaV1.2 channels by Mg2+ acting at an EF-hand motif in the COOH-terminal domain (2005). https://pmc.ncbi.nlm.nih.gov/articles/PMC2266622/ DOI: 10.1085/jgp.200509333
Complete structured claim and evidence
Lower Mg intake increased supraventricular ectopy in a randomized crossover feeding study of postmenopausal women.
Magnesium → Supraventricular ectopy source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence-system
22 completers; 81-day low and supplemented Mg periods; Holter monitoring
experimental_model
22 completers; 81-day low and supplemented Mg periods; Holter monitoring
exposure
Chemically measured mean intake: 130 mg Mg/day in the low period versus 411 mg/day in the supplemented period; 81 days per period after 10-day equilibration. These are experimental exposures, not recommendations.
limitations
Ventricular ectopy alone was not significantly increased; small cohort. Dietary copper varied independently; reported Mg effect was unaffected by copper or sequence.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
Controlled magnesium restriction produced its own measurable cardiac electrical effect.
primary_references
[klevay-2002-ectopy] Low dietary magnesium increases supraventricular ectopy (2002). https://ajcn.nutrition.org/article/S0002-9165%2823%2906154-3/fulltext DOI: 10.1093/ajcn/75.3.550
tissue
Whole-body nutrition; cardiac electrophysiology
tissue_or_cell_type
Whole-body nutrition; cardiac electrophysiology
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1318–1330
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 22 completers; 81-day low and supplemented Mg periods; Holter monitoring · source_derived_draft · unverified_draft
### low-dietary-magnesium-increases-ectopy Lower Mg intake increased supraventricular ectopy in a randomized crossover feeding study of postmenopausal women. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Controlled magnesium restriction produced its own measurable cardiac electrical effect. organism: Human tissue_or_cell_type: Whole-body nutrition; cardiac electrophysiology experimental_model: 22 completers; 81-day low and supplemented Mg periods; Holter monitoring limitations: Ventricular ectopy alone was not significantly increased; small cohort. Dietary copper varied independently; reported Mg effect was unaffected by copper or sequence. exposure: Chemically measured mean intake: 130 mg Mg/day in the low period versus 411 mg/day in the supplemented period; 81 days per period after 10-day equilibration. These are experimental exposures, not recommendations. evidence-system: 22 completers; 81-day low and supplemented Mg periods; Holter monitoring tissue: Whole-body nutrition; cardiac electrophysiology [klevay-2002-ectopy] Low dietary magnesium increases supraventricular ectopy (2002). https://ajcn.nutrition.org/article/S0002-9165%2823%2906154-3/fulltext DOI: 10.1093/ajcn/75.3.550
Complete structured claim and evidence
Mg biomarkers declined on the low-Mg diet, but hypomagnesemia, hypocalcemia and hypokalemia were not detected.
Magnesium → Serum magnesium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence-system
Crossover feeding and biochemical monitoring
experimental_model
Crossover feeding and biochemical monitoring
exposure
Chemically measured mean intake: 130 mg Mg/day in the low period versus 411 mg/day in the supplemented period; 81 days per period after 10-day equilibration. These are experimental exposures, not recommendations.
limitations
A study-specific biomarker observation; not a diagnostic rule for all normal serum values.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Human
plain_language
A normal-range serum result did not rule out the diet-related electrical phenotype in these participants.
primary_references
[klevay-2002-ectopy] Low dietary magnesium increases supraventricular ectopy (2002). https://ajcn.nutrition.org/article/S0002-9165%2823%2906154-3/fulltext DOI: 10.1093/ajcn/75.3.550
tissue
Serum, erythrocytes and urine
tissue_or_cell_type
Serum, erythrocytes and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1332–1344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crossover feeding and biochemical monitoring · source_derived_draft · unverified_draft
### low-magnesium-diet-without-hypomagnesemia Mg biomarkers declined on the low-Mg diet, but hypomagnesemia, hypocalcemia and hypokalemia were not detected. Condition category: biomarker_context nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal-range serum result did not rule out the diet-related electrical phenotype in these participants. organism: Human tissue_or_cell_type: Serum, erythrocytes and urine experimental_model: Crossover feeding and biochemical monitoring limitations: A study-specific biomarker observation; not a diagnostic rule for all normal serum values. exposure: Chemically measured mean intake: 130 mg Mg/day in the low period versus 411 mg/day in the supplemented period; 81 days per period after 10-day equilibration. These are experimental exposures, not recommendations. evidence-system: Crossover feeding and biochemical monitoring tissue: Serum, erythrocytes and urine [klevay-2002-ectopy] Low dietary magnesium increases supraventricular ectopy (2002). https://ajcn.nutrition.org/article/S0002-9165%2823%2906154-3/fulltext DOI: 10.1093/ajcn/75.3.550
Complete structured claim and evidence
Sixteen of 23 hypocalcemic magnesium-deficient patients had low circulating calcitriol.
Magnesium → Serum calcitriol concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> vitamin D/calcium regulation; direct CYP cofactor step not established.
experimental_model
Clinical metabolite measurements.
limitations
Association within an affected cohort; substrate supply, PTH and other illness can contribute.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Magnesium depletion can accompany low active vitamin D.
primary_references
[mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933
tissue_or_cell_type
Human serum; circulating mineral and vitamin D metabolites
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1346–1356
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clinical metabolite measurements. · source_derived_draft · unverified_draft
### mg-deficient-human-low-calcitriol Sixteen of 23 hypocalcemic magnesium-deficient patients had low circulating calcitriol. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium depletion can accompany low active vitamin D. organism: Homo sapiens tissue_or_cell_type: Human serum; circulating mineral and vitamin D metabolites experimental_model: Clinical metabolite measurements. limitations: Association within an affected cohort; substrate supply, PTH and other illness can contribute. cross_nutrient: Magnesium -> vitamin D/calcium regulation; direct CYP cofactor step not established. [mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933
Complete structured claim and evidence
Magnesium treatment normalized mean serum calcium, while calcitriol rose into or above normal in only five of the 23 patients.
Magnesium → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> calcium response; vitamin D normalization is not obligatory in this cohort.
experimental_model
Five to thirteen days of parenteral Mg.
limitations
Nonrandomized clinical response; calcium recovery does not prove that calcitriol rose.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Restoring magnesium did not automatically normalize every vitamin D result.
primary_references
[mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933
tissue_or_cell_type
Human serum; circulating mineral and vitamin D metabolites
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1358–1368
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five to thirteen days of parenteral Mg. · source_derived_draft · unverified_draft
### mg-calcium-recovery-precedes-calcitriol Magnesium treatment normalized mean serum calcium, while calcitriol rose into or above normal in only five of the 23 patients. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring magnesium did not automatically normalize every vitamin D result. organism: Homo sapiens tissue_or_cell_type: Human serum; circulating mineral and vitamin D metabolites experimental_model: Five to thirteen days of parenteral Mg. limitations: Nonrandomized clinical response; calcium recovery does not prove that calcitriol rose. cross_nutrient: Magnesium -> calcium response; vitamin D normalization is not obligatory in this cohort. [mg-rude1985] Low serum concentrations of 1,25-dihydroxyvitamin D in human magnesium deficiency (1985). https://pubmed.ncbi.nlm.nih.gov/3840173/ DOI: 10.1210/jcem-61-5-933
Complete structured claim and evidence
Magnesium depletion did not impair measured calcifediol-to-calcitriol conversion in these rats; isolated renal activity persisted without added Mg.
Magnesium → Calcitriol production source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium/vitamin D: qualify a universal CYP27B1 shutdown claim.
experimental_model
In-vivo tracer and isolated mitochondrial assays.
limitations
No-added-Mg buffer does not prove a metal-free preparation. This result cannot be generalized to every species or illness.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
Low magnesium did not switch off vitamin D activation in this rat experiment.
primary_references
[mg-carpenter1987] Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats (1987). https://pubmed.ncbi.nlm.nih.gov/3605332/ DOI: 10.1152/ajpendo.1987.253.1.e106
tissue_or_cell_type
Rat circulation and isolated kidney mitochondria
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1370–1380
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vivo tracer and isolated mitochondrial assays. · source_derived_draft · unverified_draft
### mg-rat-calcitriol-conversion-preserved Magnesium depletion did not impair measured calcifediol-to-calcitriol conversion in these rats; isolated renal activity persisted without added Mg. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low magnesium did not switch off vitamin D activation in this rat experiment. organism: Rattus norvegicus tissue_or_cell_type: Rat circulation and isolated kidney mitochondria experimental_model: In-vivo tracer and isolated mitochondrial assays. limitations: No-added-Mg buffer does not prove a metal-free preparation. This result cannot be generalized to every species or illness. cross_nutrient: Magnesium/vitamin D: qualify a universal CYP27B1 shutdown claim. [mg-carpenter1987] Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats (1987). https://pubmed.ncbi.nlm.nih.gov/3605332/ DOI: 10.1152/ajpendo.1987.253.1.e106
Complete structured claim and evidence
Magnesium deprivation decreased renal cyp27b1-mrna abundance in the 21-day rat experiment.
Magnesium → CYP27B1 mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> vitamin D/phosphate handling; transcript-level evidence.
experimental_model
Mg-free versus 0.05% Mg diet.
limitations
mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
The kidney made less of the message for vitamin D activation.
primary_references
[mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
tissue_or_cell_type
Rat kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1382–1392
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mg-free versus 0.05% Mg diet. · source_derived_draft · unverified_draft
### mg-deficiency-cyp27b1-transcript Magnesium deprivation decreased renal cyp27b1-mrna abundance in the 21-day rat experiment. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney made less of the message for vitamin D activation. organism: Rattus norvegicus tissue_or_cell_type: Rat kidney experimental_model: Mg-free versus 0.05% Mg diet. limitations: mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference. cross_nutrient: Magnesium -> vitamin D/phosphate handling; transcript-level evidence. [mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
Complete structured claim and evidence
Magnesium deprivation increased renal cyp24a1-mrna abundance in the 21-day rat experiment.
Magnesium → CYP24A1 mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> vitamin D/phosphate handling; transcript-level evidence.
experimental_model
Mg-free versus 0.05% Mg diet.
limitations
mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
The message for a vitamin D breakdown enzyme rose.
primary_references
[mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
tissue_or_cell_type
Rat kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1394–1404
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mg-free versus 0.05% Mg diet. · source_derived_draft · unverified_draft
### mg-deficiency-cyp24a1-transcript Magnesium deprivation increased renal cyp24a1-mrna abundance in the 21-day rat experiment. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The message for a vitamin D breakdown enzyme rose. organism: Rattus norvegicus tissue_or_cell_type: Rat kidney experimental_model: Mg-free versus 0.05% Mg diet. limitations: mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference. cross_nutrient: Magnesium -> vitamin D/phosphate handling; transcript-level evidence. [mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
Complete structured claim and evidence
Magnesium deprivation decreased renal slc34a1-mrna abundance in the 21-day rat experiment.
Magnesium → SLC34A1 mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> vitamin D/phosphate handling; transcript-level evidence.
experimental_model
Mg-free versus 0.05% Mg diet.
limitations
mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
The message for one phosphate-reabsorbing transporter fell.
primary_references
[mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
tissue_or_cell_type
Rat kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1406–1416
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mg-free versus 0.05% Mg diet. · source_derived_draft · unverified_draft
### mg-deficiency-napi2a-transcript Magnesium deprivation decreased renal slc34a1-mrna abundance in the 21-day rat experiment. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The message for one phosphate-reabsorbing transporter fell. organism: Rattus norvegicus tissue_or_cell_type: Rat kidney experimental_model: Mg-free versus 0.05% Mg diet. limitations: mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference. cross_nutrient: Magnesium -> vitamin D/phosphate handling; transcript-level evidence. [mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
Complete structured claim and evidence
Magnesium deprivation decreased renal slc34a3-mrna abundance in the 21-day rat experiment.
Magnesium → SLC34A3 mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> vitamin D/phosphate handling; transcript-level evidence.
experimental_model
Mg-free versus 0.05% Mg diet.
limitations
mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
A second phosphate-transporter message also fell.
primary_references
[mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
tissue_or_cell_type
Rat kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1418–1428
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mg-free versus 0.05% Mg diet. · source_derived_draft · unverified_draft
### mg-deficiency-napi2c-transcript Magnesium deprivation decreased renal slc34a3-mrna abundance in the 21-day rat experiment. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second phosphate-transporter message also fell. organism: Rattus norvegicus tissue_or_cell_type: Rat kidney experimental_model: Mg-free versus 0.05% Mg diet. limitations: mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference. cross_nutrient: Magnesium -> vitamin D/phosphate handling; transcript-level evidence. [mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
Complete structured claim and evidence
Magnesium assignment altered plasma 25(OH)D3 differently by baseline vitamin D: an increase near 30 ng/mL and a decrease at higher baseline concentrations.
Magnesium → Plasma calcifediol concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium <-> vitamin D status; baseline-dependent clinical endpoint.
experimental_model
Randomized 12-week ancillary analysis, 180 adults.
exposure
Personalized Mg supplementation; baseline calcium:magnesium intake ratio at least 2.6. Ratios describe enrollment, not a recommended target.
limitations
Only two participants had overt vitamin D deficiency; the trial does not show universal deficiency rescue or identify the responsible enzyme.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The vitamin D response depended on the starting level.
primary_references
[mg-dai2018] Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial (2018). https://pubmed.ncbi.nlm.nih.gov/30541089/ DOI: 10.1093/ajcn/nqy274
tissue_or_cell_type
Human plasma
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1430–1441
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized 12-week ancillary analysis, 180 adults. · source_derived_draft · unverified_draft
### mg-supplement-calcifediol-baseline-dependent Magnesium assignment altered plasma 25(OH)D3 differently by baseline vitamin D: an increase near 30 ng/mL and a decrease at higher baseline concentrations. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The vitamin D response depended on the starting level. organism: Homo sapiens tissue_or_cell_type: Human plasma experimental_model: Randomized 12-week ancillary analysis, 180 adults. limitations: Only two participants had overt vitamin D deficiency; the trial does not show universal deficiency rescue or identify the responsible enzyme. cross_nutrient: Magnesium <-> vitamin D status; baseline-dependent clinical endpoint. exposure: Personalized Mg supplementation; baseline calcium:magnesium intake ratio at least 2.6. Ratios describe enrollment, not a recommended target. [mg-dai2018] Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial (2018). https://pubmed.ncbi.nlm.nih.gov/30541089/ DOI: 10.1093/ajcn/nqy274
Complete structured claim and evidence
The trial did not detect a treatment-by-baseline-25(OH)D interaction for plasma calcitriol.
Magnesium → Plasma calcitriol concentration source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium/vitamin D: distinguish 25(OH)D from 1,25(OH)2D.
experimental_model
Same randomized ancillary analysis.
limitations
No significant interaction is not proof of no possible effect.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A change in stored vitamin D did not establish the same pattern for its active form.
primary_references
[mg-dai2018] Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial (2018). https://pubmed.ncbi.nlm.nih.gov/30541089/ DOI: 10.1093/ajcn/nqy274
tissue_or_cell_type
Human plasma
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1443–1453
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same randomized ancillary analysis. · source_derived_draft · unverified_draft
### mg-supplement-calcitriol-no-baseline-interaction The trial did not detect a treatment-by-baseline-25(OH)D interaction for plasma calcitriol. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A change in stored vitamin D did not establish the same pattern for its active form. organism: Homo sapiens tissue_or_cell_type: Human plasma experimental_model: Same randomized ancillary analysis. limitations: No significant interaction is not proof of no possible effect. cross_nutrient: Magnesium/vitamin D: distinguish 25(OH)D from 1,25(OH)2D. [mg-dai2018] Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial (2018). https://pubmed.ncbi.nlm.nih.gov/30541089/ DOI: 10.1093/ajcn/nqy274
Complete structured claim and evidence
Recombinant human PHOSPHO1 showed strong Mg dependence when hydrolyzing phosphoethanolamine and phosphocholine.
Mg2+ → Phosphoethanolamine/phosphocholine phosphatase PHOSPHO1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium -> PHOSPHO1 -> phosphate production; joins the existing calcium PHOSPHO1 records.
experimental_model
Purified recombinant phosphatase assays.
limitations
Enzyme evidence does not measure the effect of oral Mg on bone; substrate Km values are not Mg deficiency thresholds.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Magnesium helps a phosphate-releasing enzyme already connected to calcium mineralization.
primary_references
[mg-roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/bj20040511
tissue_or_cell_type
Purified recombinant human PHOSPHO1
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1455–1465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant phosphatase assays. · source_derived_draft · unverified_draft
### mg-phospho1-cofactor Recombinant human PHOSPHO1 showed strong Mg dependence when hydrolyzing phosphoethanolamine and phosphocholine. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps a phosphate-releasing enzyme already connected to calcium mineralization. organism: Homo sapiens tissue_or_cell_type: Purified recombinant human PHOSPHO1 experimental_model: Purified recombinant phosphatase assays. limitations: Enzyme evidence does not measure the effect of oral Mg on bone; substrate Km values are not Mg deficiency thresholds. cross_nutrient: Magnesium -> PHOSPHO1 -> phosphate production; joins the existing calcium PHOSPHO1 records. [mg-roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/bj20040511
Complete structured claim and evidence
Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity.
Mg2+ → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization.
experimental_model
Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate.
limitations
Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
This mineralization enzyme needs the right metals in different sites.
primary_references
[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1467–1477
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft
### mg-zinc-alpl-reconstitution Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mineralization enzyme needs the right metals in different sites. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. limitations: Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
Calcium at TNAP site M3 supported about 40% of the activity of Mg/Zn-TNAP at pH 7.4 and 9.8.
Calcium ion → Mg2+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium/Mg substitution at one enzyme site, not whole-body interchangeability.
experimental_model
Recombinant enzyme comparison. Activity was measured using artificial pNPP substrate.
limitations
Site-specific substitution is not evidence that dietary calcium replaces magnesium requirements. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Calcium can occupy this magnesium site, but gives a different enzyme response.
primary_references
[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1479–1489
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme comparison. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft
### mg-alpl-calcium-partial-substitution Calcium at TNAP site M3 supported about 40% of the activity of Mg/Zn-TNAP at pH 7.4 and 9.8. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium can occupy this magnesium site, but gives a different enzyme response. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Recombinant enzyme comparison. Activity was measured using artificial pNPP substrate. limitations: Site-specific substitution is not evidence that dietary calcium replaces magnesium requirements. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Calcium/Mg substitution at one enzyme site, not whole-body interchangeability. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
Very high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH.
Calcium ion → Tissue-nonspecific alkaline phosphatase ALPL / TNAP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium/Zn/Mg interaction depends on site occupancy and local conditions.
experimental_model
Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate.
limitations
Local experimental concentrations cannot be converted to dietary dose cutoffs. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The same calcium ion can activate one site and interfere with another.
primary_references
[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
tissue_or_cell_type
Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1491–1501
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft
### mg-alpl-high-calcium-zinc-displacement Very high calcium displaced or competed with Zn at TNAP M1/M2 sites and reduced activity; concentrations depended on pH. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same calcium ion can activate one site and interfere with another. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Purified TNAP concentration/pH experiment. Activity was measured using artificial pNPP substrate. limitations: Local experimental concentrations cannot be converted to dietary dose cutoffs. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Calcium/Zn/Mg interaction depends on site occupancy and local conditions. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874
Complete structured claim and evidence
Insulin receptor autophosphorylation was reduced about 50% in muscle preparations from Mg-deficient rats, despite similar insulin binding.
Magnesium → Insulin receptor autophosphorylation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> insulin signaling -> carbohydrate handling.
experimental_model
Partially purified rat gastrocnemius receptors.
limitations
A depletion experiment; not isolated Mg binding to a particular receptor site.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
The receptor could still bind insulin, but its downstream activation was impaired.
primary_references
[mg-suarez1995] Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats (1995). https://pubmed.ncbi.nlm.nih.gov/8582534/ DOI: 10.1007/bf00401757
tissue_or_cell_type
Rat gastrocnemius receptor preparations and perfused hindquarter
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1503–1513
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified rat gastrocnemius receptors. · source_derived_draft · unverified_draft
### mg-deficiency-insr-autophosphorylation Insulin receptor autophosphorylation was reduced about 50% in muscle preparations from Mg-deficient rats, despite similar insulin binding. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor could still bind insulin, but its downstream activation was impaired. organism: Rattus norvegicus tissue_or_cell_type: Rat gastrocnemius receptor preparations and perfused hindquarter experimental_model: Partially purified rat gastrocnemius receptors. limitations: A depletion experiment; not isolated Mg binding to a particular receptor site. cross_nutrient: Magnesium -> insulin signaling -> carbohydrate handling. [mg-suarez1995] Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats (1995). https://pubmed.ncbi.nlm.nih.gov/8582534/ DOI: 10.1007/bf00401757
Complete structured claim and evidence
Mg-deficient rat muscle had lower glucose uptake at submaximal insulin; basal and maximal-insulin uptake were preserved.
Magnesium → Insulin-stimulated glucose uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium/insulin/glucose; impaired sensitivity is distinct from absence of transport.
experimental_model
Perfused rat hindquarter.
limitations
Muscle GLUT4 abundance was similar; the experiment does not establish a single causal intermediate.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
The response became less sensitive rather than completely stopping.
primary_references
[mg-suarez1995] Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats (1995). https://pubmed.ncbi.nlm.nih.gov/8582534/ DOI: 10.1007/bf00401757
tissue_or_cell_type
Rat gastrocnemius receptor preparations and perfused hindquarter
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1515–1525
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perfused rat hindquarter. · source_derived_draft · unverified_draft
### mg-deficiency-muscle-insulin-response Mg-deficient rat muscle had lower glucose uptake at submaximal insulin; basal and maximal-insulin uptake were preserved. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response became less sensitive rather than completely stopping. organism: Rattus norvegicus tissue_or_cell_type: Rat gastrocnemius receptor preparations and perfused hindquarter experimental_model: Perfused rat hindquarter. limitations: Muscle GLUT4 abundance was similar; the experiment does not establish a single causal intermediate. cross_nutrient: Magnesium/insulin/glucose; impaired sensitivity is distinct from absence of transport. [mg-suarez1995] Impaired tyrosine-kinase activity of muscle insulin receptors from hypomagnesaemic rats (1995). https://pubmed.ncbi.nlm.nih.gov/8582534/ DOI: 10.1007/bf00401757
Complete structured claim and evidence
Insulin increased TRPM6 surface abundance and channel activity through a PI3K- and RAC1-dependent pathway.
Insulin → TRPM6 abundance at the cell surface source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Insulin -> magnesium-channel trafficking; complements the separate Mg -> insulin-response findings.
experimental_model
Expression-cell electrophysiology and surface fluorescence.
limitations
Combined pathway perturbations; no unspecified PI3K isoform assigned and no universal clinical feedback loop proven.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Insulin can affect the magnesium entry machinery as well as glucose metabolism.
primary_references
[mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109
tissue_or_cell_type
TRPM6-expressing cells; plasma membrane
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1527–1537
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression-cell electrophysiology and surface fluorescence. · source_derived_draft · unverified_draft
### mg-insulin-trpm6-surface-regulation Insulin increased TRPM6 surface abundance and channel activity through a PI3K- and RAC1-dependent pathway. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Insulin can affect the magnesium entry machinery as well as glucose metabolism. organism: Homo sapiens tissue_or_cell_type: TRPM6-expressing cells; plasma membrane experimental_model: Expression-cell electrophysiology and surface fluorescence. limitations: Combined pathway perturbations; no unspecified PI3K isoform assigned and no universal clinical feedback loop proven. cross_nutrient: Insulin -> magnesium-channel trafficking; complements the separate Mg -> insulin-response findings. [mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109
Complete structured claim and evidence
Insulin failed to activate tested TRPM6 V1393I and K1584E variants.
TRPM6 V1393I variant → Insulin source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Insulin/TRPM6/Mg interaction can depend on genotype.
experimental_model
Mutant-versus-wild-type channel assays.
limitations
Nearby phosphorylation-site effects are proposed; association with pregnancy glycemia does not prove nutritional causality.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A change in the channel can interrupt the signal even when insulin is present.
primary_references
[mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109
tissue_or_cell_type
TRPM6-expressing cells; plasma membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1539–1549
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutant-versus-wild-type channel assays. · source_derived_draft · unverified_draft
### mg-trpm6-variants-insulin-response Insulin failed to activate tested TRPM6 V1393I and K1584E variants. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A change in the channel can interrupt the signal even when insulin is present. organism: Homo sapiens tissue_or_cell_type: TRPM6-expressing cells; plasma membrane experimental_model: Mutant-versus-wild-type channel assays. limitations: Nearby phosphorylation-site effects are proposed; association with pregnancy glycemia does not prove nutritional causality. cross_nutrient: Insulin/TRPM6/Mg interaction can depend on genotype. [mg-nair2012] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy (2012). https://pubmed.ncbi.nlm.nih.gov/22733750/ DOI: 10.1073/pnas.1113811109
Complete structured claim and evidence
Magnesium treatment lowered HOMA-IR compared with placebo in hypomagnesemic adults with type 2 diabetes receiving glibenclamide.
Magnesium → HOMA-IR estimate of insulin resistance source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium -> insulin/glucose endpoints; treatment context matters.
experimental_model
63-person, 16-week randomized trial.
exposure
Eligibility serum Mg at most 0.74 mmol/L. End-study HOMA-IR means 3.8 versus 5.0.
limitations
HOMA is a surrogate, not a clamp; renal impairment was excluded. Not proof that all diabetes responds to Mg.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
One trial found improved insulin-resistance estimates in a specific low-magnesium group.
primary_references
[mg-rodriguezmoran2003] Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial (2003). https://pubmed.ncbi.nlm.nih.gov/12663588/ DOI: 10.2337/diacare.26.4.1147
tissue_or_cell_type
Human blood-based metabolic endpoints
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1551–1562
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 63-person, 16-week randomized trial. · source_derived_draft · unverified_draft
### mg-diabetes-homa-trial2003 Magnesium treatment lowered HOMA-IR compared with placebo in hypomagnesemic adults with type 2 diabetes receiving glibenclamide. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: One trial found improved insulin-resistance estimates in a specific low-magnesium group. organism: Homo sapiens tissue_or_cell_type: Human blood-based metabolic endpoints experimental_model: 63-person, 16-week randomized trial. limitations: HOMA is a surrogate, not a clamp; renal impairment was excluded. Not proof that all diabetes responds to Mg. cross_nutrient: Magnesium -> insulin/glucose endpoints; treatment context matters. exposure: Eligibility serum Mg at most 0.74 mmol/L. End-study HOMA-IR means 3.8 versus 5.0. [mg-rodriguezmoran2003] Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial (2003). https://pubmed.ncbi.nlm.nih.gov/12663588/ DOI: 10.2337/diacare.26.4.1147
Complete structured claim and evidence
Magnesium increased serum Mg but did not significantly change the primary clamp outcome in insulin-treated adults with low serum Mg.
Magnesium → Hyperinsulinemic-euglycemic clamp glucose infusion rate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium/insulin/glucose: biochemical repletion and clinical response are separate.
experimental_model
14-person, six-week randomized crossover trial.
exposure
15 mmol/day trial exposure, not advice. Clamp M 4.6 versus 4.4 mg/kg/min; p=0.108.
limitations
Small trial and modest biochemical change; not proof of zero effect. Differs from the 2003 trial in treatment, duration and endpoint, not a fabricated scientific contradiction.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Raising the blood magnesium value did not establish improved insulin sensitivity in this trial.
primary_references
[mg-drenthen2024] Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial (2024). https://pubmed.ncbi.nlm.nih.gov/37922013/ DOI: 10.1007/s00125-023-06029-9
tissue_or_cell_type
Human whole-body glucose clamp and blood measurements
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1564–1575
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 14-person, six-week randomized crossover trial. · source_derived_draft · unverified_draft
### mg-diabetes-clamp-trial2024 Magnesium increased serum Mg but did not significantly change the primary clamp outcome in insulin-treated adults with low serum Mg. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Raising the blood magnesium value did not establish improved insulin sensitivity in this trial. organism: Homo sapiens tissue_or_cell_type: Human whole-body glucose clamp and blood measurements experimental_model: 14-person, six-week randomized crossover trial. limitations: Small trial and modest biochemical change; not proof of zero effect. Differs from the 2003 trial in treatment, duration and endpoint, not a fabricated scientific contradiction. cross_nutrient: Magnesium/insulin/glucose: biochemical repletion and clinical response are separate. exposure: 15 mmol/day trial exposure, not advice. Clamp M 4.6 versus 4.4 mg/kg/min; p=0.108. [mg-drenthen2024] Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial (2024). https://pubmed.ncbi.nlm.nih.gov/37922013/ DOI: 10.1007/s00125-023-06029-9
Complete structured claim and evidence
High-dose supplemental zinc reduced measured Mg absorption in the pooled metabolic-balance groups.
Zinc sulfate → Intestinal magnesium absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc -> magnesium availability; calcium intake recorded as context.
experimental_model
Adult men; three dietary calcium strata.
exposure
142 mg Zn/day as sulfate; calcium 230, 500 or 800 mg/day. Only the 500-mg stratum individually significant; pooled groups significant.
limitations
142 mg zinc/day is a high experimental exposure; ordinary food zinc effects and a shared transporter were not established.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Large zinc exposure can interfere with magnesium uptake.
primary_references
[mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
tissue_or_cell_type
Human intestinal absorption and metabolic balance
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1577–1588
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adult men; three dietary calcium strata. · source_derived_draft · unverified_draft
### mg-high-zinc-lowers-absorption High-dose supplemental zinc reduced measured Mg absorption in the pooled metabolic-balance groups. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Large zinc exposure can interfere with magnesium uptake. organism: Homo sapiens tissue_or_cell_type: Human intestinal absorption and metabolic balance experimental_model: Adult men; three dietary calcium strata. limitations: 142 mg zinc/day is a high experimental exposure; ordinary food zinc effects and a shared transporter were not established. cross_nutrient: Zinc -> magnesium availability; calcium intake recorded as context. exposure: 142 mg Zn/day as sulfate; calcium 230, 500 or 800 mg/day. Only the 500-mg stratum individually significant; pooled groups significant. [mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
Complete structured claim and evidence
The pooled high-zinc groups also had lower Mg balance.
Zinc sulfate → Whole-body magnesium balance source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc/Mg intake balance; exposure-dependent.
experimental_model
Same adult metabolic-balance experiment.
limitations
Not a molecular transporter competition assay or evidence that every zinc dose depletes Mg.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Absorption interference was accompanied by a change in net magnesium balance.
primary_references
[mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
tissue_or_cell_type
Human intestinal absorption and metabolic balance
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1590–1600
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same adult metabolic-balance experiment. · source_derived_draft · unverified_draft
### mg-high-zinc-lowers-balance The pooled high-zinc groups also had lower Mg balance. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Absorption interference was accompanied by a change in net magnesium balance. organism: Homo sapiens tissue_or_cell_type: Human intestinal absorption and metabolic balance experimental_model: Same adult metabolic-balance experiment. limitations: Not a molecular transporter competition assay or evidence that every zinc dose depletes Mg. cross_nutrient: Zinc/Mg intake balance; exposure-dependent. [mg-spencer1994] Inhibitory effects of zinc on magnesium balance and magnesium absorption in man (1994). https://pubmed.ncbi.nlm.nih.gov/7836627/ DOI: 10.1080/07315724.1994.10718438
Complete structured claim and evidence
Adding phytate to matched-Mg bread meals reduced fractional apparent Mg absorption in a dose-dependent pattern.
Phytic acid / phytate → Intestinal magnesium absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Dietary phytate -> magnesium uptake; mineral content and fractional absorption are distinct.
experimental_model
Two human crossover stable-isotope studies, 8-9 adults each.
exposure
1.49 mmol phytate: 32.5% to 13.0%; 0.75 mmol: 32.2% to 24.0%; 3.6 mmol Mg per meal.
limitations
Absorption is measured; mineral complexation was not isolated. Does not show that whole grains are net Mg-poor.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A food component can reduce how much magnesium reaches the body from a meal.
primary_references
[mg-bohn2004] Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans (2004). https://pubmed.ncbi.nlm.nih.gov/14985216/ DOI: 10.1093/ajcn/79.3.418
tissue_or_cell_type
Human intestinal absorption estimated by fecal isotope recovery
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1602–1613
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human crossover stable-isotope studies, 8-9 adults each. · source_derived_draft · unverified_draft
### mg-phytate-lowers-absorption Adding phytate to matched-Mg bread meals reduced fractional apparent Mg absorption in a dose-dependent pattern. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A food component can reduce how much magnesium reaches the body from a meal. organism: Homo sapiens tissue_or_cell_type: Human intestinal absorption estimated by fecal isotope recovery experimental_model: Two human crossover stable-isotope studies, 8-9 adults each. limitations: Absorption is measured; mineral complexation was not isolated. Does not show that whole grains are net Mg-poor. cross_nutrient: Dietary phytate -> magnesium uptake; mineral content and fractional absorption are distinct. exposure: 1.49 mmol phytate: 32.5% to 13.0%; 0.75 mmol: 32.2% to 24.0%; 3.6 mmol Mg per meal. [mg-bohn2004] Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans (2004). https://pubmed.ncbi.nlm.nih.gov/14985216/ DOI: 10.1093/ajcn/79.3.418
Complete structured claim and evidence
Higher calcium intake did not significantly alter Mg absorption, excretion or modeled balance in five adolescent girls.
Calcium → Whole-body magnesium balance source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium -> magnesium balance: a bounded null interaction.
experimental_model
Randomized crossover; Mg isotope kinetics.
exposure
Calcium 800 versus 1800 mg/day; Mg intakes about 305 versus 286 mg/day.
limitations
Very small and population-specific; a null result is not equivalence for all intakes or ages.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Calcium and magnesium do not always compete enough to change measured balance.
primary_references
[mg-sojka1997] Magnesium kinetics in adolescent girls determined using stable isotopes: effects of high and low calcium intake (1997). https://pubmed.ncbi.nlm.nih.gov/9277559/ DOI: 10.1152/ajpregu.1997.273.2.r710
tissue_or_cell_type
Human whole-body Mg isotope kinetics
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1615–1626
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover; Mg isotope kinetics. · source_derived_draft · unverified_draft
### mg-high-calcium-no-kinetic-difference Higher calcium intake did not significantly alter Mg absorption, excretion or modeled balance in five adolescent girls. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium and magnesium do not always compete enough to change measured balance. organism: Homo sapiens tissue_or_cell_type: Human whole-body Mg isotope kinetics experimental_model: Randomized crossover; Mg isotope kinetics. limitations: Very small and population-specific; a null result is not equivalence for all intakes or ages. cross_nutrient: Calcium -> magnesium balance: a bounded null interaction. exposure: Calcium 800 versus 1800 mg/day; Mg intakes about 305 versus 286 mg/day. [mg-sojka1997] Magnesium kinetics in adolescent girls determined using stable isotopes: effects of high and low calcium intake (1997). https://pubmed.ncbi.nlm.nih.gov/9277559/ DOI: 10.1152/ajpregu.1997.273.2.r710
Complete structured claim and evidence
Magnesium citrate dissolved more readily than oxide in the tested gastric-acid simulation.
Magnesium citrate → Magnesium oxide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Formulation/acid environment -> magnesium availability.
experimental_model
In-vitro water/acid comparison.
limitations
Specific preparations and assay conditions, not an exhaustive ranking of commercial supplements.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Cell-free chemical preparation
plain_language
Chemical form can change dissolution before absorption.
primary_references
[mg-lindberg1990] Magnesium bioavailability from magnesium citrate and magnesium oxide (1990). https://pubmed.ncbi.nlm.nih.gov/2407766/ DOI: 10.1080/07315724.1990.10720349
tissue_or_cell_type
Simulated gastric solutions or human urinary Mg response, as specified in model
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1628–1638
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vitro water/acid comparison. · source_derived_draft · unverified_draft
### mg-citrate-oxide-solubility Magnesium citrate dissolved more readily than oxide in the tested gastric-acid simulation. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chemical form can change dissolution before absorption. organism: Cell-free chemical preparation tissue_or_cell_type: Simulated gastric solutions or human urinary Mg response, as specified in model experimental_model: In-vitro water/acid comparison. limitations: Specific preparations and assay conditions, not an exhaustive ranking of commercial supplements. cross_nutrient: Formulation/acid environment -> magnesium availability. [mg-lindberg1990] Magnesium bioavailability from magnesium citrate and magnesium oxide (1990). https://pubmed.ncbi.nlm.nih.gov/2407766/ DOI: 10.1080/07315724.1990.10720349
Complete structured claim and evidence
The tested citrate oral load produced a larger urinary Mg increment than the oxide load in healthy volunteers.
Magnesium citrate → Magnesium oxide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium chemical form -> absorption proxy.
experimental_model
Healthy-volunteer oral-load comparison.
exposure
25 mmol Mg experimental oral loads; historical study exposure, not dosage advice.
limitations
Urinary response is not tissue restoration or proof of superior clinical outcomes.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A formulation difference was reflected in a short-term absorption proxy.
primary_references
[mg-lindberg1990] Magnesium bioavailability from magnesium citrate and magnesium oxide (1990). https://pubmed.ncbi.nlm.nih.gov/2407766/ DOI: 10.1080/07315724.1990.10720349
tissue_or_cell_type
Simulated gastric solutions or human urinary Mg response, as specified in model
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1640–1651
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Healthy-volunteer oral-load comparison. · source_derived_draft · unverified_draft
### mg-citrate-oxide-urinary-response The tested citrate oral load produced a larger urinary Mg increment than the oxide load in healthy volunteers. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A formulation difference was reflected in a short-term absorption proxy. organism: Homo sapiens tissue_or_cell_type: Simulated gastric solutions or human urinary Mg response, as specified in model experimental_model: Healthy-volunteer oral-load comparison. limitations: Urinary response is not tissue restoration or proof of superior clinical outcomes. cross_nutrient: Magnesium chemical form -> absorption proxy. exposure: 25 mmol Mg experimental oral loads; historical study exposure, not dosage advice. [mg-lindberg1990] Magnesium bioavailability from magnesium citrate and magnesium oxide (1990). https://pubmed.ncbi.nlm.nih.gov/2407766/ DOI: 10.1080/07315724.1990.10720349
Complete structured claim and evidence
Free ATP and nonhydrolyzable ATP analogues inhibited beta-cell KATP channels without requiring phosphorylation.
ATP → Pancreatic beta-cell ATP-sensitive potassium current source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Free ATP must be distinguished from its magnesium complex.
experimental_model
Rat beta-cell inside-out patches.
limitations
Excised patches do not reproduce all intact-cell metabolic regulation.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Rat
plain_language
ATP can close the potassium channel through nucleotide regulation.
primary_references
[ashcroft-1989-magnesium] ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions (1989). https://pmc.ncbi.nlm.nih.gov/articles/PMC1189219/ DOI: 10.1113/jphysiol.1989.sp017765
tissue_or_cell_type
Pancreatic beta-cell membrane
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 786–796
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat beta-cell inside-out patches. · source_derived_draft · unverified_draft
### k-beta-atp-inhibition Free ATP and nonhydrolyzable ATP analogues inhibited beta-cell KATP channels without requiring phosphorylation. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP can close the potassium channel through nucleotide regulation. organism: Rat tissue_or_cell_type: Pancreatic beta-cell membrane experimental_model: Rat beta-cell inside-out patches. limitations: Excised patches do not reproduce all intact-cell metabolic regulation. cross_nutrient: Free ATP must be distinguished from its magnesium complex. [ashcroft-1989-magnesium] ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions (1989). https://pmc.ncbi.nlm.nih.gov/articles/PMC1189219/ DOI: 10.1113/jphysiol.1989.sp017765
Complete structured claim and evidence
Human PDXK crystallography placed ginkgotoxin at the pyridoxal-binding site alongside MgATP.
Ginkgotoxin / 4-prime-O-methylpyridoxine → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Purified human PDXK; crystallography and inhibition kinetics
exposure
2.15 angstrom ternary crystal structure.
limitations
Binding in a purified protein does not establish brain concentrations.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The structure directly locates the competing toxin.
primary_references
[gandhi-2012-pdxk-inhibitors] Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040954 DOI: 10.1371/journal.pone.0040954
tissue_or_cell_type
Purified recombinant protein; no intact tissue
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1208–1218
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human PDXK; crystallography and inhibition kinetics · source_derived_draft · unverified_draft
### b6-neuro-ginkgotoxin-binding Human PDXK crystallography placed ginkgotoxin at the pyridoxal-binding site alongside MgATP. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The structure directly locates the competing toxin. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human PDXK; crystallography and inhibition kinetics limitations: Binding in a purified protein does not establish brain concentrations. exposure: 2.15 angstrom ternary crystal structure. [gandhi-2012-pdxk-inhibitors] Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040954 DOI: 10.1371/journal.pone.0040954
Complete structured claim and evidence
Human PANK3 structures resolved Mg2+ in nucleotide-bound substrate and product complexes, directly connecting magnesium to the B5-phosphorylation machinery.
Mg2+ → Human pantothenate kinase 3 / PANK3 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments
exposure
In-vitro biochemical exposure; concentrations not extracted.
limitations
Structures used AMPPNP, ADP and related nucleotide complexes; ATP–Mg binding was assessed biochemically. This demonstrates catalytic-complex participation, not a dietary magnesium threshold or supplementation requirement.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
Magnesium is part of the nucleotide complex used by PANK3.
primary_references
[b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 496–507
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments · source_derived_draft · unverified_draft
### b5-bio-pank3-magnesium Human PANK3 structures resolved Mg2+ in nucleotide-bound substrate and product complexes, directly connecting magnesium to the B5-phosphorylation machinery. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium is part of the nucleotide complex used by PANK3. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments limitations: Structures used AMPPNP, ADP and related nucleotide complexes; ATP–Mg binding was assessed biochemically. This demonstrates catalytic-complex participation, not a dietary magnesium threshold or supplementation requirement. exposure: In-vitro biochemical exposure; concentrations not extracted. cross_nutrient: true [b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
Complete structured claim and evidence
Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline.
Phosphocholine → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified-enzyme substrate assay
limitations
This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
A second phospholipid-headgroup metabolite can supply phosphate.
primary_references
[roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
tissue_or_cell_type
Recombinant enzyme
Calcium: mechanism-first literature curation (2026-09-17) · lines 908–917
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme substrate assay · source_derived_draft · unverified_draft
### phospho1-phosphocholine-hydrolysis Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second phospholipid-headgroup metabolite can supply phosphate. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified-enzyme substrate assay limitations: This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor. [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
Complete structured claim and evidence
Added magnesium did not enhance human TYMS reaction rates under conditions where bacterial TYMS differed.
Mg2+ → Human thymidylate synthase / TYMS source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Species-specific boundary on a proposed magnesium-folate interaction.
experimental_model
Comparative enzyme kinetics
exposure
Assay conditions described in the linked primary study.
limitations
Assay-specific negative result, not proof of magnesium-independent DNA synthesis.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Magnesium effects on bacterial enzymes cannot be assumed for human TYMS.
primary_references
[islam-2018] Bacterial versus human thymidylate synthase: Kinetics and functionality (2018). https://pubmed.ncbi.nlm.nih.gov/29715278/ DOI: 10.1371/journal.pone.0196506
tissue_or_cell_type
Cell-free
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 985–996
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Comparative enzyme kinetics · source_derived_draft · unverified_draft
### human-tyms-magnesium-not-stimulatory Added magnesium did not enhance human TYMS reaction rates under conditions where bacterial TYMS differed. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium effects on bacterial enzymes cannot be assumed for human TYMS. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Comparative enzyme kinetics limitations: Assay-specific negative result, not proof of magnesium-independent DNA synthesis. exposure: Assay conditions described in the linked primary study. cross_nutrient: Species-specific boundary on a proposed magnesium-folate interaction. [islam-2018] Bacterial versus human thymidylate synthase: Kinetics and functionality (2018). https://pubmed.ncbi.nlm.nih.gov/29715278/ DOI: 10.1371/journal.pone.0196506
Complete structured claim and evidence
Human erythrocyte pyridoxal phosphatase required divalent cations; magnesium activated PLP hydrolysis with Michaelis-Menten behavior.
Mg2+ → Human pyridoxal phosphatase / PDXP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium participates in both sides of B6 phosphate cycling.
evidence_location
Indexed abstract: divalent-cation kinetics at pH 7.4, 37 C
experimental_model
Purified human erythrocyte pyridoxal phosphatase kinetics.
exposure
pH 7.4, 37 C; Mg2+ titration.
limitations
Other metals also activated in vitro; does not establish net PLP response to changing dietary magnesium.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Magnesium supports B6 dephosphorylation as well as activation.
primary_references
[fonda1995] Kinetic mechanism and divalent metal activation of human erythrocyte pyridoxal phosphatase. (1995). https://pubmed.ncbi.nlm.nih.gov/7625842/ DOI: 10.1016/0003-9861(95)90018-7
tissue_or_cell_type
Erythrocyte enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 282–294
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human erythrocyte pyridoxal phosphatase kinetics. · source_derived_draft · unverified_draft
### b6-transport-pdxp-magnesium Human erythrocyte pyridoxal phosphatase required divalent cations; magnesium activated PLP hydrolysis with Michaelis-Menten behavior. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium supports B6 dephosphorylation as well as activation. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Purified human erythrocyte pyridoxal phosphatase kinetics. limitations: Other metals also activated in vitro; does not establish net PLP response to changing dietary magnesium. exposure: pH 7.4, 37 C; Mg2+ titration. evidence_location: Indexed abstract: divalent-cation kinetics at pH 7.4, 37 C cross_nutrient: Magnesium participates in both sides of B6 phosphate cycling. [fonda1995] Kinetic mechanism and divalent metal activation of human erythrocyte pyridoxal phosphatase. (1995). https://pubmed.ncbi.nlm.nih.gov/7625842/ DOI: 10.1016/0003-9861(95)90018-7
Complete structured claim and evidence
Median lactate normalized across overall treatment groups, but not in the low-magnesium subgroup receiving the thiamine-containing preparation alone.
Magnesium sulfate → Plasma lactate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium status -> response during thiamine-containing treatment.
experimental_model
Low-Mg thiamine-only subgroup n=22; two-hour measurement.
exposure
Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations.
limitations
Subgroup finding; no direct PDH flux or universal magnesium gate demonstrated. Pabrinex is multivitamins.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Low magnesium identified a subgroup whose lactate did not normalize with the vitamin infusion alone.
primary_references
[b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
tissue_or_cell_type
Plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1611–1622
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Low-Mg thiamine-only subgroup n=22; two-hour measurement. · source_derived_draft · unverified_draft
### b1-aws-low-mg-lactate-response Median lactate normalized across overall treatment groups, but not in the low-magnesium subgroup receiving the thiamine-containing preparation alone. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low magnesium identified a subgroup whose lactate did not normalize with the vitamin infusion alone. organism: Homo sapiens tissue_or_cell_type: Plasma experimental_model: Low-Mg thiamine-only subgroup n=22; two-hour measurement. limitations: Subgroup finding; no direct PDH flux or universal magnesium gate demonstrated. Pabrinex is multivitamins. cross_nutrient: Magnesium status -> response during thiamine-containing treatment. exposure: Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations. [b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
Complete structured claim and evidence
Potassium-depleted MDCT cells showed reduced Mg2+ uptake in a magnesium-recovery assay.
Intracellular potassium content → Cellular magnesium influx source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Cellular K depletion decreases magnesium entry in this DCT model.
evidence_location
Primary abstract; potassium-depleted-cell Mg uptake comparison.
experimental_model
Cultured MDCT potassium depletion; fluorescence Mg-recovery assay
limitations
Intracellular depletion is distinct from low extracellular K alone; TRPM6 was not identified.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Mus musculus cell line
plain_language
Depleting cellular potassium made it harder for these kidney cells to take up magnesium.
primary_references
[dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141
tissue_or_cell_type
Distal convoluted tubule cell model
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 484–495
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured MDCT potassium depletion; fluorescence Mg-recovery assay · source_derived_draft · unverified_draft
### renal-cellular-k-depletion-lowers-mg-influx Potassium-depleted MDCT cells showed reduced Mg2+ uptake in a magnesium-recovery assay. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Depleting cellular potassium made it harder for these kidney cells to take up magnesium. organism: Mus musculus cell line tissue_or_cell_type: Distal convoluted tubule cell model experimental_model: Cultured MDCT potassium depletion; fluorescence Mg-recovery assay limitations: Intracellular depletion is distinct from low extracellular K alone; TRPM6 was not identified. cross_nutrient: Cellular K depletion decreases magnesium entry in this DCT model. evidence_location: Primary abstract; potassium-depleted-cell Mg uptake comparison. [dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141
Complete structured claim and evidence
Purified mouse TPK1 formed ATP and thiamine from ThDP plus AMP under high-AMP, magnesium-containing conditions.
Mouse thiamine pyrophosphokinase 1 → ATP source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg dependence remains distinct from physiological net reaction direction.
evidence-scope
Recombinant enzyme
evidence_locator
Reaction definition and sections 2.2 and 3.3
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}]
experimental_model
Purified recombinant mouse TPK1; forward and reverse reactions.
limitations
High AMP/Mg requirements do not establish meaningful reverse flux in humans.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Mus musculus
plain_language
The activation chemistry can run backward experimentally.
primary_references
[sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
tissue_or_cell_type
Recombinant enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 373–386
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant mouse TPK1; forward and reverse reactions. · source_derived_draft · unverified_draft
### b1-mouse-tpk1-reverse-reaction Purified mouse TPK1 formed ATP and thiamine from ThDP plus AMP under high-AMP, magnesium-containing conditions. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The activation chemistry can run backward experimentally. organism: Mus musculus tissue_or_cell_type: Recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reactions. limitations: High AMP/Mg requirements do not establish meaningful reverse flux in humans. cross_nutrient: Mg dependence remains distinct from physiological net reaction direction. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}] evidence_locator: Reaction definition and sections 2.2 and 3.3 evidence-scope: Recombinant enzyme [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
Kinase kinetic experiments identified MgATP as the preferred phosphate-donor complex under the reported physiological assay conditions.
Magnesium-ATP complex → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-B6 activation chemistry.
evidence_location
Indexed abstract and publisher abstract; human enzyme findings only
experimental_model
Purified recombinant human and E. coli pyridoxal kinases.
exposure
MgATP versus ZnATP kinetic comparisons.
limitations
Metal preference depends on assay conditions and does not prove magnesium supplementation improves B6 status.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Magnesium helps supply ATP to B6 activation.
primary_references
[disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
tissue_or_cell_type
Purified human enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 189–201
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human and E. coli pyridoxal kinases. · source_derived_draft · unverified_draft
### b6-transport-pdxk-mgatp Kinase kinetic experiments identified MgATP as the preferred phosphate-donor complex under the reported physiological assay conditions. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps supply ATP to B6 activation. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human and E. coli pyridoxal kinases. limitations: Metal preference depends on assay conditions and does not prove magnesium supplementation improves B6 status. exposure: MgATP versus ZnATP kinetic comparisons. evidence_location: Indexed abstract and publisher abstract; human enzyme findings only cross_nutrient: Magnesium-B6 activation chemistry. [disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
Complete structured claim and evidence
Thiocyanate-induced hyperpolarization restored Mg2+ uptake in potassium-depleted MDCT cells.
DCT membrane potential → Cellular magnesium influx source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
The K-depletion effect on Mg entry is partly recoverable by membrane polarization.
evidence_location
Primary abstract; SCN- rescue experiment.
experimental_model
SCN- voltage manipulation after cell K depletion
limitations
Supports partial voltage mediation; does not establish an in vivo repletion strategy.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Mus musculus cell line
plain_language
Restoring the electrical driving force helped magnesium enter despite prior potassium depletion.
primary_references
[dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141
tissue_or_cell_type
Distal convoluted tubule cell model
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 497–508
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SCN- voltage manipulation after cell K depletion · source_derived_draft · unverified_draft
### renal-hyperpolarization-rescues-mg-after-k-depletion Thiocyanate-induced hyperpolarization restored Mg2+ uptake in potassium-depleted MDCT cells. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring the electrical driving force helped magnesium enter despite prior potassium depletion. organism: Mus musculus cell line tissue_or_cell_type: Distal convoluted tubule cell model experimental_model: SCN- voltage manipulation after cell K depletion limitations: Supports partial voltage mediation; does not establish an in vivo repletion strategy. cross_nutrient: The K-depletion effect on Mg entry is partly recoverable by membrane polarization. evidence_location: Primary abstract; SCN- rescue experiment. [dai-1997-k-mg] Cellular mechanisms of chlorothiazide and cellular potassium depletion on Mg2+ uptake in mouse distal convoluted tubule cells (1997). https://pubmed.ncbi.nlm.nih.gov/9083264/ DOI: 10.1038/ki.1997.141
Complete structured claim and evidence
Magnesium-bound GCAP1, rather than metal-free GCAP1, activated RetGC1 under low-calcium assay conditions.
Mg2+ → GCAP1 / GUCA1A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg2+ and Ca2+ regulate a sensor in vitamin A-dependent phototransduction recovery.
experimental_model
Purified protein metal-binding and cyclase assays
limitations
No dietary magnesium deficiency or human night-vision outcome was measured.
nutrient_topic
Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
organism
Recombinant protein biochemical system
plain_language
Magnesium occupancy lets the calcium sensor stimulate cGMP recovery.
primary_references
[peshenko-2006] Ca2+ and Mg2+ binding properties of GCAP-1. Evidence that Mg2+-bound form is the physiological activator of photoreceptor guanylyl cyclase (2006). https://pubmed.ncbi.nlm.nih.gov/16793776/ DOI: 10.1074/jbc.M600257200
tissue_or_cell_type
Photoreceptor-protein model
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 973–983
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified protein metal-binding and cyclase assays · source_derived_draft · unverified_draft
### a-vision-magnesium-gcap1 Magnesium-bound GCAP1, rather than metal-free GCAP1, activated RetGC1 under low-calcium assay conditions. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium occupancy lets the calcium sensor stimulate cGMP recovery. organism: Recombinant protein biochemical system tissue_or_cell_type: Photoreceptor-protein model experimental_model: Purified protein metal-binding and cyclase assays limitations: No dietary magnesium deficiency or human night-vision outcome was measured. cross_nutrient: Mg2+ and Ca2+ regulate a sensor in vitamin A-dependent phototransduction recovery. [peshenko-2006] Ca2+ and Mg2+ binding properties of GCAP-1. Evidence that Mg2+-bound form is the physiological activator of photoreceptor guanylyl cyclase (2006). https://pubmed.ncbi.nlm.nih.gov/16793776/ DOI: 10.1074/jbc.M600257200
Complete structured claim and evidence
The trial found no significant between-group effect on its primary endpoint of change in erythrocyte transketolase activity.
Magnesium sulfate → Blood transketolase activity source_derived_draftungraded
Experimental context and source evidence
experimental_model
115 analyzed; biochemical measurement two hours after treatment.
exposure
Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations.
limitations
Does not refute molecular Mg requirements or prove no effect in deficient tissues; almost all participants lacked low erythrocyte ThDP.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The enzyme endpoint did not improve significantly across treatment groups.
primary_references
[b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
tissue_or_cell_type
Erythrocytes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1599–1609
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 115 analyzed; biochemical measurement two hours after treatment. · source_derived_draft · unverified_draft
### b1-aws-mg-transketolase-null The trial found no significant between-group effect on its primary endpoint of change in erythrocyte transketolase activity. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme endpoint did not improve significantly across treatment groups. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: 115 analyzed; biochemical measurement two hours after treatment. limitations: Does not refute molecular Mg requirements or prove no effect in deficient tissues; almost all participants lacked low erythrocyte ThDP. exposure: Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations. [b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x
Complete structured claim and evidence
MgADP potentiated cloned Kir6.2/SUR1 current through intact SUR1 nucleotide-binding machinery.
Magnesium-ADP complex → Kir6.2-SUR1 ATP-sensitive potassium channel source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
MgADP supplies a magnesium-dependent regulatory input to potassium conductance.
experimental_model
Xenopus oocyte cloned-channel patches.
limitations
Heterologous channel biochemistry, not nutritional magnesium depletion.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Xenopus expression system
plain_language
Magnesium-bound ADP helps keep this potassium channel active.
primary_references
[gribble-1997-sur1] The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC1169713/ DOI: 10.1093/emboj/16.6.1145
tissue_or_cell_type
Oocyte membrane
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 810–820
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Xenopus oocyte cloned-channel patches. · source_derived_draft · unverified_draft
### k-mgadp-sur1-activation MgADP potentiated cloned Kir6.2/SUR1 current through intact SUR1 nucleotide-binding machinery. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium-bound ADP helps keep this potassium channel active. organism: Xenopus expression system tissue_or_cell_type: Oocyte membrane experimental_model: Xenopus oocyte cloned-channel patches. limitations: Heterologous channel biochemistry, not nutritional magnesium depletion. cross_nutrient: MgADP supplies a magnesium-dependent regulatory input to potassium conductance. [gribble-1997-sur1] The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC1169713/ DOI: 10.1093/emboj/16.6.1145
Complete structured claim and evidence
Purified human FADS2 showed a strict MgCl2 requirement in the reported spectrophotometric FAD-synthesis assay.
Mg2+ → Human FAD synthetase isoform 2 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium is a cofactor for a vitamin B2 activation step.
evidence_location
Abstract and activity assay
experimental_model
Recombinant human FADS2 expressed in E. coli and purified
exposure
MgCl2 requirement tested in purified enzyme assays.
limitations
Assay-specific metal dependence does not quantify human dietary magnesium effects on flavins.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens protein
plain_language
Magnesium supports enzymatic conversion of FMN into FAD.
primary_references
[transport-fads2-2007] Over-expression in Escherichia coli, purification and characterization of isoform 2 of human FAD synthetase. (2007). https://doi.org/10.1016/j.pep.2006.09.002 DOI: 10.1016/j.pep.2006.09.002
tissue_or_cell_type
Purified enzyme
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 333–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human FADS2 expressed in E. coli and purified · source_derived_draft · unverified_draft
### transport-flad1-magnesium-requirement Purified human FADS2 showed a strict MgCl2 requirement in the reported spectrophotometric FAD-synthesis assay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium supports enzymatic conversion of FMN into FAD. organism: Homo sapiens protein tissue_or_cell_type: Purified enzyme experimental_model: Recombinant human FADS2 expressed in E. coli and purified limitations: Assay-specific metal dependence does not quantify human dietary magnesium effects on flavins. exposure: MgCl2 requirement tested in purified enzyme assays. cross_nutrient: Magnesium is a cofactor for a vitamin B2 activation step. evidence_location: Abstract and activity assay [transport-fads2-2007] Over-expression in Escherichia coli, purification and characterization of isoform 2 of human FAD synthetase. (2007). https://doi.org/10.1016/j.pep.2006.09.002 DOI: 10.1016/j.pep.2006.09.002
Complete structured claim and evidence
Low baseline serum magnesium was associated with subsequent refeeding syndrome in the cohort.
Serum magnesium concentration → Electrolyte and fluid disorder during refeeding source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Three syndrome events among 243 adults.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
Too few events for robust multivariable regression; association does not identify a universal causal bottleneck.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A mineral shortage was a risk signal alongside poor prior intake.
primary_references
[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
tissue_or_cell_type
Serum and clinical course
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1746–1756
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three syndrome events among 243 adults. · source_derived_draft · unverified_draft
### b1-refeeding-low-mg-association Low baseline serum magnesium was associated with subsequent refeeding syndrome in the cohort. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mineral shortage was a risk signal alongside poor prior intake. organism: Homo sapiens tissue_or_cell_type: Serum and clinical course experimental_model: Three syndrome events among 243 adults. limitations: Too few events for robust multivariable regression; association does not identify a universal causal bottleneck. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
Complete structured claim and evidence
Human PDXK showed lower substrate Km with potassium than sodium, whereas sodium supported over twice the maximal activity.
Potassium ion → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Potassium/sodium-B6 enzyme kinetics.
evidence_location
Full text: Metal binding and enzyme activity; Figure 1
experimental_model
Purified recombinant human PDXK kinetics and crystallography.
exposure
Kinetic assays at pH 7.3.
limitations
Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Potassium and sodium affect different kinetic properties.
primary_references
[safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107
tissue_or_cell_type
Purified human enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 203–215
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PDXK kinetics and crystallography. · source_derived_draft · unverified_draft
### b6-transport-pdxk-k-na Human PDXK showed lower substrate Km with potassium than sodium, whereas sodium supported over twice the maximal activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium and sodium affect different kinetic properties. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human PDXK kinetics and crystallography. limitations: Lower Km is not a direct binding constant; results do not define dietary sodium/potassium effects. exposure: Kinetic assays at pH 7.3. evidence_location: Full text: Metal binding and enzyme activity; Figure 1 cross_nutrient: Potassium/sodium-B6 enzyme kinetics. [safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107
Complete structured claim and evidence
Rat liver/hepatocyte pathway experiments supported activation of 2-hydroxy-fatty acid to its CoA ester before ThDP-dependent cleavage; whole-pathway assays required ATP, CoA, Mg2+, ThDP and NAD+.
2-Hydroxystearate → 2-Hydroxystearoyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation.
evidence
[{"paper_key": "foulon-2005-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Intact/permeabilized rat hepatocytes and liver preparations.
limitations
Whole-pathway requirements cannot all be assigned to the isolated lyase.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD.
primary_references
[foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200
tissue_or_cell_type
Liver
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1003–1015
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intact/permeabilized rat hepatocytes and liver preparations. · source_derived_draft · unverified_draft
### b1-alpha-oxidation-activation-before-cleavage Rat liver/hepatocyte pathway experiments supported activation of 2-hydroxy-fatty acid to its CoA ester before ThDP-dependent cleavage; whole-pathway assays required ATP, CoA, Mg2+, ThDP and NAD+. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Intact/permeabilized rat hepatocytes and liver preparations. limitations: Whole-pathway requirements cannot all be assigned to the isolated lyase. evidence: [{"paper_key": "foulon-2005-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation. nutrient: Thiamine (vitamin B1) [foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200
Complete structured claim and evidence
Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate.
Human pantothenate kinase 3 / PANK3 → Pantothenate (vitamin B5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments
exposure
In-vitro biochemical exposure; concentrations not extracted.
limitations
Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
PANK3 starts vitamin B5 activation by adding phosphate.
primary_references
[b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 483–494
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments · source_derived_draft · unverified_draft
### b5-bio-pank3-phosphorylation Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: PANK3 starts vitamin B5 activation by adding phosphate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments limitations: Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here. exposure: In-vitro biochemical exposure; concentrations not extracted. cross_nutrient: true [b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
Complete structured claim and evidence
ATPgammaS binding was detected for wild-type PDXK but not A228T under the ITC conditions; A228T also required higher MgATP for half-maximal activity.
Human PDXK Ala228Thr → ATP gamma S source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 3B,E
experimental_model
Human families, dried blood spots, recombinant PDXK variants.
exposure
ATPgammaS ITC; variable MgATP kinetics.
limitations
ATPgammaS is an analog; absence of detectable binding is assay-specific.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The variant disrupts nucleotide handling.
primary_references
[chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
tissue_or_cell_type
Purified human enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 217–228
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human families, dried blood spots, recombinant PDXK variants. · source_derived_draft · unverified_draft
### b6-transport-pdxk-a228t-atp ATPgammaS binding was detected for wild-type PDXK but not A228T under the ITC conditions; A228T also required higher MgATP for half-maximal activity. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The variant disrupts nucleotide handling. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Human families, dried blood spots, recombinant PDXK variants. limitations: ATPgammaS is an analog; absence of detectable binding is assay-specific. exposure: ATPgammaS ITC; variable MgATP kinetics. evidence_location: Figure 3B,E [chelban2019] PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation. (2019). https://pubmed.ncbi.nlm.nih.gov/31187503/ DOI: 10.1002/ana.25524
Complete structured claim and evidence
Human PDXK assays directly measured ATP-dependent conversion of pyridoxal to PLP, a reaction distinct from PNPO oxidation.
Pyridoxal kinase / PDXK → Pyridoxal source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Separates the B6 phosphorylation step from the B2-dependent oxidation step.
evidence_location
Abstract
experimental_model
Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures.
exposure
Purified-enzyme assay
limitations
This biochemical route does not establish that dietary pyridoxal bypasses all consequences of PNPO disease.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Not every route to active B6 passes through PNPO.
primary_references
[safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1192–1204
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures. · source_derived_draft · unverified_draft
### b2-pdxk-pyridoxal-route Human PDXK assays directly measured ATP-dependent conversion of pyridoxal to PLP, a reaction distinct from PNPO oxidation. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every route to active B6 passes through PNPO. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PDXK expressed in E. coli; PL-to-PLP kinetics and unliganded/MgATP-bound structures. limitations: This biochemical route does not establish that dietary pyridoxal bypasses all consequences of PNPO disease. exposure: Purified-enzyme assay cross_nutrient: Separates the B6 phosphorylation step from the B2-dependent oxidation step. evidence_location: Abstract [safo2007] Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation. (2007). https://pubmed.ncbi.nlm.nih.gov/17766369/ DOI: 10.1110/ps.073022107
Complete structured claim and evidence
SUR1 K719A or K1384M substitution impaired MgADP potentiation of cloned KATP currents.
SUR1 K719A variant → Kir6.2-SUR1 ATP-sensitive potassium channel source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
A machinery defect interrupts magnesium-nucleotide regulation without demonstrating ion deficiency.
experimental_model
Mutant versus wild-type Xenopus patches.
limitations
Engineered substitutions are not evidence of dietary K or Mg deficiency.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Xenopus expression system
plain_language
Damaged nucleotide machinery can disrupt potassium-channel regulation.
primary_references
[gribble-1997-sur1] The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC1169713/ DOI: 10.1093/emboj/16.6.1145
tissue_or_cell_type
Oocyte membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 822–832
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutant versus wild-type Xenopus patches. · source_derived_draft · unverified_draft
### k-sur1-mutations-mgadp SUR1 K719A or K1384M substitution impaired MgADP potentiation of cloned KATP currents. Condition category: machinery_impairment nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Damaged nucleotide machinery can disrupt potassium-channel regulation. organism: Xenopus expression system tissue_or_cell_type: Oocyte membrane experimental_model: Mutant versus wild-type Xenopus patches. limitations: Engineered substitutions are not evidence of dietary K or Mg deficiency. cross_nutrient: A machinery defect interrupts magnesium-nucleotide regulation without demonstrating ion deficiency. [gribble-1997-sur1] The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide (1997). https://pmc.ncbi.nlm.nih.gov/articles/PMC1169713/ DOI: 10.1093/emboj/16.6.1145
Complete structured claim and evidence
Human PHOSPHO1 hydrolyzes phosphoethanolamine, releasing inorganic phosphate and ethanolamine; the enzyme requires Mg2+ in the assay.
Phosphoethanolamine → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified-enzyme substrate assay
limitations
Catalytic capacity does not quantify phosphate supply in vivo; Pi denotes pH-dependent protonation states.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
PHOSPHO1 can release phosphate from a membrane-headgroup metabolite.
primary_references
[roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
tissue_or_cell_type
Recombinant enzyme; mineralizing-cell context
Calcium: mechanism-first literature curation (2026-09-17) · lines 897–906
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme substrate assay · source_derived_draft · unverified_draft
### phospho1-phosphoethanolamine-hydrolysis Human PHOSPHO1 hydrolyzes phosphoethanolamine, releasing inorganic phosphate and ethanolamine; the enzyme requires Mg2+ in the assay. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PHOSPHO1 can release phosphate from a membrane-headgroup metabolite. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme; mineralizing-cell context experimental_model: Purified-enzyme substrate assay limitations: Catalytic capacity does not quantify phosphate supply in vivo; Pi denotes pH-dependent protonation states. [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
Complete structured claim and evidence
Purified rat peroxisomal HACL1 cleaved 2-hydroxy-3-methylhexadecanoyl-CoA into formyl-CoA and 2-methylpentadecanal, with activity dependent on ThDP and Mg2+.
Rat 2-hydroxyacyl-CoA lyase 1 → 2-Hydroxy-3-methylhexadecanoyl-CoA source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct B1/Mg dependence of a lipid-cleavage enzyme; not evidence that dietary Mg universally limits alpha oxidation.
evidence
[{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Purified rat liver lyase; defined-substrate product identification.
limitations
Defined branched substrate and rat purified enzyme; not a human deficiency experiment.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
B1 and magnesium support a carbon-cleavage reaction in fatty-acid alpha oxidation. Here the measured products are a one-carbon CoA ester and a shortened aldehyde.
primary_references
[foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039
tissue_or_cell_type
Liver peroxisomes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 976–988
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver lyase; defined-substrate product identification. · source_derived_draft · unverified_draft
### b1-hacl1-rat-branched-cleavage Purified rat peroxisomal HACL1 cleaved 2-hydroxy-3-methylhexadecanoyl-CoA into formyl-CoA and 2-methylpentadecanal, with activity dependent on ThDP and Mg2+. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 and magnesium support a carbon-cleavage reaction in fatty-acid alpha oxidation. Here the measured products are a one-carbon CoA ester and a shortened aldehyde. organism: Rattus norvegicus tissue_or_cell_type: Liver peroxisomes experimental_model: Purified rat liver lyase; defined-substrate product identification. limitations: Defined branched substrate and rat purified enzyme; not a human deficiency experiment. evidence: [{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Direct B1/Mg dependence of a lipid-cleavage enzyme; not evidence that dietary Mg universally limits alpha oxidation. nutrient: Thiamine (vitamin B1) [foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039
Complete structured claim and evidence
D71N markedly decreased recombinant human TPK1 catalytic turnover.
Human TPK1 D71N experimental variant → Human thiamine pyrophosphokinase 1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Recombinant enzyme
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/onozuka-2003-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1438}]
experimental_model
Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis.
limitations
Engineered mutation; not an isolated clinical magnesium effect.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Disrupting an active-site residue impairs B1 activation.
primary_references
[onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
tissue_or_cell_type
Recombinant enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 358–371
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. · source_derived_draft · unverified_draft
### b1-tpk1-d71n-catalysis D71N markedly decreased recombinant human TPK1 catalytic turnover. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disrupting an active-site residue impairs B1 activation. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. limitations: Engineered mutation; not an isolated clinical magnesium effect. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/onozuka-2003-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1438}] evidence_locator: Abstract evidence-scope: Recombinant enzyme [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
Human RFK crystallized with MgADP and FMN showed magnesium coordination by an FMN phosphate oxygen and Asn36.
Mg2+ → Riboflavin kinase / RFK source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium supports the chemistry used to activate vitamin B2; no blood-magnesium threshold is established.
evidence_location
Abstract; metal-coordination structural analysis
experimental_model
Product-bound human RFK crystallography
exposure
Co-crystallization with MgADP and FMN.
limitations
A metal-bound enzyme structure is not a clinical magnesium-deficiency or supplementation experiment.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Magnesium participates directly in the RFK active site.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 306–318
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product-bound human RFK crystallography · source_derived_draft · unverified_draft
### transport-rfk-magnesium-coordination Human RFK crystallized with MgADP and FMN showed magnesium coordination by an FMN phosphate oxygen and Asn36. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium participates directly in the RFK active site. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Product-bound human RFK crystallography limitations: A metal-bound enzyme structure is not a clinical magnesium-deficiency or supplementation experiment. exposure: Co-crystallization with MgADP and FMN. cross_nutrient: Magnesium supports the chemistry used to activate vitamin B2; no blood-magnesium threshold is established. evidence_location: Abstract; metal-coordination structural analysis [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Adding 2 mM Mg shifted apparent total-ATP inhibition from Ki 4 to 26 micromolar in excised beta-cell patches.
Mg2+ → Pancreatic beta-cell ATP-sensitive potassium current source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-nucleotide chemistry modifies potassium-channel gating; no dietary magnesium effect quantified.
experimental_model
Inside-out rat patches; Mg-free versus 2 mM Mg.
limitations
Assay concentrations are not clinical magnesium thresholds.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Rat
plain_language
Magnesium changed how the potassium channel responded to total ATP.
primary_references
[ashcroft-1989-magnesium] ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions (1989). https://pmc.ncbi.nlm.nih.gov/articles/PMC1189219/ DOI: 10.1113/jphysiol.1989.sp017765
tissue_or_cell_type
Pancreatic beta-cell membrane
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 798–808
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inside-out rat patches; Mg-free versus 2 mM Mg. · source_derived_draft · unverified_draft
### k-beta-mg-atp-speciation Adding 2 mM Mg shifted apparent total-ATP inhibition from Ki 4 to 26 micromolar in excised beta-cell patches. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium changed how the potassium channel responded to total ATP. organism: Rat tissue_or_cell_type: Pancreatic beta-cell membrane experimental_model: Inside-out rat patches; Mg-free versus 2 mM Mg. limitations: Assay concentrations are not clinical magnesium thresholds. cross_nutrient: Magnesium-nucleotide chemistry modifies potassium-channel gating; no dietary magnesium effect quantified. [ashcroft-1989-magnesium] ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions (1989). https://pmc.ncbi.nlm.nih.gov/articles/PMC1189219/ DOI: 10.1113/jphysiol.1989.sp017765
Complete structured claim and evidence
The purified human liver MTHFS reaction requires ATP and Mg2+ and is an ADP-forming cyclo-ligase reaction.
ATP → Human methenyltetrahydrofolate synthetase / MTHFS source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and ATP support folate interconversion.
experimental_model
Purified liver enzyme
exposure
Controlled enzyme assay with ATP and magnesium.
limitations
Cofactor dependence does not establish a dietary magnesium threshold.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
ATP supplies energy for this magnesium-dependent folate conversion.
primary_references
[bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5
tissue_or_cell_type
Liver-derived, cell-free
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1255–1266
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified liver enzyme · source_derived_draft · unverified_draft
### mthfs-atp-magnesium-dependence The purified human liver MTHFS reaction requires ATP and Mg2+ and is an ADP-forming cyclo-ligase reaction. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP supplies energy for this magnesium-dependent folate conversion. organism: Homo sapiens tissue_or_cell_type: Liver-derived, cell-free experimental_model: Purified liver enzyme limitations: Cofactor dependence does not establish a dietary magnesium threshold. exposure: Controlled enzyme assay with ATP and magnesium. cross_nutrient: Magnesium and ATP support folate interconversion. [bertrand-1987] Human liver methenyltetrahydrofolate synthetase: improved purification and increased affinity for folate polyglutamate substrates (1987). https://pubmed.ncbi.nlm.nih.gov/3801490/ DOI: 10.1016/0167-4838(87)90004-5
Complete structured claim and evidence
The NAD+-dependent rat MTHFD2L dehydrogenase assay requires magnesium in the presence of phosphate.
Mg2+ → Rat mitochondrial MTHFD2L source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct magnesium/phosphate requirement in folate oxidation.
experimental_model
Cofactor omission/addition assays
exposure
Assay conditions described in the linked primary study.
limitations
No dietary magnesium threshold follows from these assays.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Rattus norvegicus
plain_language
Magnesium supports this NAD-linked folate reaction.
primary_references
[shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
tissue_or_cell_type
Cell-free
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 862–873
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor omission/addition assays · source_derived_draft · unverified_draft
### rat-mthfd2l-magnesium-phosphate The NAD+-dependent rat MTHFD2L dehydrogenase assay requires magnesium in the presence of phosphate. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium supports this NAD-linked folate reaction. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Cofactor omission/addition assays limitations: No dietary magnesium threshold follows from these assays. exposure: Assay conditions described in the linked primary study. cross_nutrient: Direct magnesium/phosphate requirement in folate oxidation. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
Complete structured claim and evidence
Acetyl-CoA stabilizes an inactive human PANK3 dimer conformation, whereas ATP–Mg favors the active state; biochemical analyses showed coordinated switching of its two active sites.
Acetyl-CoA → Human pantothenate kinase 3 / PANK3 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments
exposure
In-vitro biochemical exposure; concentrations not extracted.
limitations
Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
Accumulated acyl-CoA can slow the first step of new CoA production.
primary_references
[b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 509–520
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments · source_derived_draft · unverified_draft
### b5-bio-pank3-feedback Acetyl-CoA stabilizes an inactive human PANK3 dimer conformation, whereas ATP–Mg favors the active state; biochemical analyses showed coordinated switching of its two active sites. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Accumulated acyl-CoA can slow the first step of new CoA production. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments limitations: Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here. exposure: In-vitro biochemical exposure; concentrations not extracted. cross_nutrient: false [b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
Complete structured claim and evidence
Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay.
Mn2+ → COLGALT1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human COLGALT1 metal-substitution assays.
limitations
Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive.
organism
Human
plain_language
Manganese is a catalytic partner for this collagen-sugar enzyme.
primary_references
[colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 447–455
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human COLGALT1 metal-substitution assays. · source_derived_draft · unverified_draft
### manganese-colgalt1 Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay. Plain language: Manganese is a catalytic partner for this collagen-sugar enzyme. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified human COLGALT1 metal-substitution assays. limitations: Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive. [colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
Complete structured claim and evidence

Availability and dependencies

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

Low magnesium alone can reduce the sodium entry that drives potassium secretion

Condition: nutrient_deficiency · Dietary Mg restriction with dietary sodium maintained in the mouse experiments.

Normal role: ENaC sodium entry and ROMK conductance jointly influence potassium secretion.

Recorded consequence: Lower ENaC activity can restrain potassium loss despite hypomagnesemia.

Scope: C57BL/6J dietary experiments.

Combined sodium and magnesium restriction favors potassium loss in mice

Condition: nutrient_deficiency · Combined low-Na/low-Mg diet for seven days.

Normal role: Mg blocks ROMK outward current while ENaC sodium entry supplies a secretory electrical driving force.

Recorded consequence: Preserved ENaC, higher ROMK activity and lower plasma K occur together.

Scope: Native channels and blood measurements in the specified mouse model.

Human prolonged magnesium depletion impairs potassium maintenance

Condition: nutrient_deficiency · Prolonged purified Mg-deficient feeding in two elderly men.

Normal role: Adequate Mg supports potassium homeostasis.

Recorded consequence: Hypokalemia and increased potassium replacement needs developed; Mg repletion raised serum K.

Scope: Small historical within-person depletion/repletion experiment.

Low magnesium intake reduced the measured night signal in rats

Condition: nutrient_deficiency · Four-week magnesium-deficient rat diet

Normal role: Adequate magnesium intake accompanied the higher dark-phase melatonin concentration.

Recorded consequence: Lower mean plasma melatonin without an obvious phase shift.

Scope: Rat dietary magnesium deficiency; not dietary melatonin deficiency

Magnesium treatment improves potassium balance in hypokalemic ICU patients

Condition: biomarker_context · Hypokalemia in critically ill adults undergoing usual care and randomized additional Mg treatment.

Normal role: Potassium replacement increases available potassium, with retention influenced by concurrent physiology.

Recorded consequence: More positive potassium input-minus-urine balance.

Scope: Randomized ICU trial; baseline cellular Mg deficiency was not established.

Low magnesium is not reliably rescued by boron

Condition: nutrient_deficiency · Dietary magnesium restricted to about 118 mg/day in the metabolic unit.

Normal role: Adequate magnesium intake supports positive magnesium balance.

Recorded consequence: Magnesium balance became negative; boron did not obviously change the overall deprivation response.

Scope: Human postmenopausal feeding study; dietary magnesium deficiency is distinct from low boron intake.

Severe magnesium deficiency can impair PTH secretion and calcium recovery

Condition: nutrient_deficiency · Hypomagnesemia with hypocalcemia in the clinical series.

Normal role: PTH release and target-organ responses help sustain circulating calcium.

Recorded consequence: PTH may be inappropriately low; Mg repletion can restore PTH before calcium normalizes.

Scope: Human clinical repletion and hormone-challenge evidence.

Selective magnesium depletion alters the PTH and calcitriol response

Condition: nutrient_deficiency · Three weeks of experimental low-Mg diet in initially normal adults.

Normal role: Falling calcium normally recruits a compensatory PTH response.

Recorded consequence: PTH compensation and calcitriol response to infused PTH were blunted.

Scope: Controlled before/after depletion study.

PTH secretion can fail while response to administered PTH remains intact

Condition: nutrient_deficiency · Withdrawal of Mg supplementation in a child with primary hypomagnesemia.

Normal role: Secretion and tissue responsiveness are separable parts of PTH physiology.

Recorded consequence: Hypocalcemia occurred with low PTH but preserved responses to parathyroid extract.

Scope: One child, biochemical phenotype; no genotype assumed.

Very low magnesium strengthens inhibitory CaSR-associated signaling in the tested cells

Condition: nutrient_deficiency · Extracellular Mg experimentally lowered in dispersed human parathyroid cells or CaSR expression systems.

Normal role: CaSR-associated G proteins regulate PTH release through second messengers.

Recorded consequence: Inhibitory signaling increases while PTH release falls.

Scope: Human hyperparathyroid tissue cells plus recombinant mechanistic models.

A G protein mutant separates the intracellular Mg mechanism from receptor ion sensing

Condition: machinery_impairment · Engineered R209C substitution lowers apparent Mg sensitivity.

Normal role: Wild-type Galpha-i1 nucleotide exchange responds to Mg in the assay.

Recorded consequence: The usual Mg dependence of receptor-stimulated GTP analogue binding is lost over the tested range.

Scope: Experimental mutant, not dietary deficiency or an identified patient genotype.

Genetic disruption of a cofactor site

Condition: machinery_impairment · Engineered disease-associated alphaV138M substitution.

Normal role: Mg and ThDP occupy the E1 cofactor pocket.

Recorded consequence: Altered Mg/ThDP geometry with regulatory-loop disorder.

Scope: Recombinant human E1 structure and reconstituted complex.

Hypomagnesemia accompanying delayed thiamine response

Condition: nutrient_deficiency · Documented hypomagnesemia in patients receiving thiamine.

Normal role: Mg participates in thiamine activation and some ThDP enzyme systems.

Recorded consequence: Delayed biochemical or neurological improvement, followed by improvement during Mg correction.

Scope: Small uncontrolled human reports.

Inherited TRPM6-associated magnesium loss

Condition: machinery_impairment · Biallelic pathogenic TRPM6 variants.

Normal role: Epithelial Mg entry supports organismal Mg balance.

Recorded consequence: Severe low serum magnesium, often secondary low calcium.

Scope: Affected human families.

Intestinal Trpm6 deletion

Condition: machinery_impairment · Villin1-Cre intestinal Trpm6 deletion.

Normal role: Intestinal Mg uptake maintains systemic supply.

Recorded consequence: Reduced serum and bone magnesium with renal conservation.

Scope: Six-month-old male conditional knockout mice.

Renal Trpm6 deletion under tested mouse conditions

Condition: machinery_impairment · Ksp-Cre kidney-specific Trpm6 deletion.

Normal role: Renal epithelial Mg transport contributes to Mg recovery.

Recorded consequence: Serum and urine Mg were maintained in the tested conditions.

Scope: Six-month-old male conditional knockout mice.

Dietary magnesium depletion changes manganese status and liver PC in rats

Condition: nutrient_deficiency · Mg-deficient versus normal synthetic diet for two weeks, starting at three weeks of age.

Normal role: Adequate Mg supports normal mineral metabolism and enzyme function.

Recorded consequence: Tissue/plasma Mn declined and crude-mitochondrial liver PC activity fell.

Scope: Forty young male Wistar rats.

Cellular TRPM7 deletion

Condition: machinery_impairment · Targeted TRPM7 deletion in DT40 cells.

Normal role: TRPM7 contributes to cellular Mg entry.

Recorded consequence: Cellular magnesium depletion and impaired growth, rescued by increased extracellular Mg.

Scope: Cultured chicken B-cell line.

Intestinal Trpm7 loss and multiple mineral deficits

Condition: machinery_impairment · Intestinal Trpm7 deletion in suckling mice.

Normal role: TRPM7 supports epithelial handling of several divalent nutrients.

Recorded consequence: Low magnesium, calcium and zinc availability.

Scope: Early postnatal mice.

Pro-EGF sorting defect

Condition: machinery_impairment · Homozygous EGF P1070L.

Normal role: Basolateral EGF signaling supports TRPM6 activity.

Recorded consequence: Reduced basolateral ligand delivery and impaired Mg retention.

Scope: Human kindred plus polarized-cell experiments.

Claudin-16-associated renal Mg loss

Condition: machinery_impairment · Pathogenic CLDN16 variants or model-specific RNAi depletion.

Normal role: TAL tight-junction selectivity supports divalent-cation reabsorption.

Recorded consequence: Magnesium and calcium renal loss.

Scope: Human families and separately specified mouse RNAi model.

Claudin-19-associated renal Mg loss

Condition: machinery_impairment · Biallelic CLDN19 variants.

Normal role: Claudin-19 participates in renal tight-junction ion handling.

Recorded consequence: Renal magnesium wasting with additional organ phenotypes.

Scope: Affected human families.

Reciprocal claudin RNAi in mouse kidney

Condition: machinery_impairment · Claudin-16 or claudin-19 RNAi in separate transgenic mouse lines.

Normal role: Claudin complexes support tight-junction ion selectivity.

Recorded consequence: The partner claudin was displaced from TAL tight junctions.

Scope: The reported reciprocal RNAi models.

CNNM2 variant-associated disease

Condition: machinery_impairment · Pathogenic CNNM2 variants.

Normal role: CNNM2 supports Mg homeostasis and neural development.

Recorded consequence: Hypomagnesemia and a neurodevelopmental phenotype.

Scope: Five human families and supporting model experiments.

Mouse Slc41a1 deletion

Condition: machinery_impairment · Constitutive Slc41a1 knockout.

Normal role: SLC41A1 can support cellular Mg efflux in expression systems.

Recorded consequence: No detectable genotype effect on systemic Mg measures under tested diets.

Scope: Mice on standard or Mg-restricted diet.

Yeast mitochondrial Mrs2p loss

Condition: machinery_impairment · Yeast mrs2 deletion.

Normal role: Mrs2p supports rapid Mg uptake into the matrix.

Recorded consequence: Loss of the rapid mitochondrial Mg influx component.

Scope: Isolated yeast mitochondria.

Experimental extracellular magnesium withdrawal

Condition: nutrient_deficiency · Removal of Mg from neuronal bathing solution.

Normal role: Extracellular Mg imposes voltage-dependent NMDA current block.

Recorded consequence: Relief of inward-current block and reduced voltage dependence.

Scope: Cultured mouse spinal neurons.

CaV1.2 regulatory-site substitutions

Condition: machinery_impairment · Engineered EF-hand substitutions.

Normal role: Intracellular Mg modulates channel activity through an EF-hand-associated mechanism.

Recorded consequence: Changed Mg sensitivity of recombinant currents.

Scope: tsA-201 expression system.

Low dietary magnesium and cardiac ectopy

Condition: nutrient_deficiency · Controlled lower-Mg diet for an 81-day period.

Normal role: Dietary Mg supplies tissue pools used in electrophysiology.

Recorded consequence: More supraventricular ectopy and lower Mg biomarkers.

Scope: 22 postmenopausal women in crossover feeding study.

Serum markers during controlled low magnesium intake

Condition: biomarker_context · Controlled lower-Mg diet for an 81-day period.

Normal role: Dietary Mg supplies tissue pools used in electrophysiology.

Recorded consequence: More supraventricular ectopy and lower Mg biomarkers.

Scope: 22 postmenopausal women in crossover feeding study.

Magnesium depletion can accompany low active vitamin D.

Condition: nutrient_deficiency · Hypocalcemia with magnesium deficiency.

Normal role: Magnesium status interacts with calcium regulation and vitamin D physiology.

Recorded consequence: Calcium and calcitriol responses can recover on different timescales.

Scope: Clinical cohort; circulating metabolites.

Low magnesium did not switch off vitamin D activation in this rat experiment.

Condition: nutrient_deficiency · Experimental dietary magnesium depletion.

Normal role: Renal conversion supplies active vitamin D.

Recorded consequence: Vitamin D metabolic effects depend on the measured system.

Scope: Rat isotope conversion and isolated mitochondrial assays.

The kidney made less of the message for vitamin D activation.

Condition: nutrient_deficiency · Twenty-one days of Mg-free diet.

Normal role: Kidney vitamin D metabolism and sodium-phosphate transport contribute to mineral homeostasis.

Recorded consequence: Cyp27b1, Cyp24a1 and phosphate-transporter transcripts shifted in different directions.

Scope: Rat kidney mRNA abundance.

The receptor could still bind insulin, but its downstream activation was impaired.

Condition: nutrient_deficiency · Four days of a low-Mg diet.

Normal role: Insulin receptor kinase activity helps muscle respond to insulin.

Recorded consequence: Receptor autophosphorylation and submaximal insulin-stimulated glucose uptake were lower.

Scope: Rat muscle receptors and perfused hindquarter.

A change in the channel can interrupt the signal even when insulin is present.

Condition: machinery_impairment · TRPM6 V1393I or K1584E substitution.

Normal role: Insulin stimulates wild-type TRPM6 in the tested system.

Recorded consequence: Insulin activation of the channel was lost.

Scope: Expression-cell experiments.

Low magnesium during alcohol withdrawal

Condition: nutrient_deficiency · Alcohol withdrawal with low serum magnesium despite mostly normal/high erythrocyte ThDP.

Normal role: Magnesium and thiamine support separate steps of cofactor use and metabolism.

Recorded consequence: Lactate response differed by magnesium status and intervention.

Scope: 2022 trial; subgroup findings after two hours.

The sources

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

Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

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

Does MgADP activate OGDHC, or do Mg and ADP act independently?The 2000 speciation interpretation assigns enhanced activation to MgADP; the 2011 reanalysis argues that separate Mg and ADP effects explain the same data more parsimoniously.Read the recorded disagreement
Is SLC41A1-associated magnesium efflux obligatorily sodium dependent?Human-SLC41A1 fluorescence experiments found strong Na dependence; mouse-SLC41A1 isotope experiments found efflux without Na.Read the recorded disagreement

Open questions in this collection

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

Which molecular steps explain persistent low calcitriol after magnesium and calcium normalize in particular patients?Clinical metabolite changes cannot isolate CYP cofactor chemistry, substrate delivery, PTH responsiveness or recovery time.
Which magnesium-dependent pathways actually mediate changes in insulin sensitivity in humans?Rat receptor assays and heterogeneous human supplementation trials do not establish one universal causal chain.
What molecular step accounts for zinc-associated reduction in human Mg absorption at the studied high intake?Balance measurements did not identify a shared transporter or prove simple competitive binding.
Do oral magnesium interventions alter PHOSPHO1 or ALPL activity enough to change human skeletal outcomes?Enzyme metal dependence and human clinical nutritional causation are different levels of evidence.
Which calcium:magnesium intake ratios, if any, predict a reproducible individual response?Trial enrollment ratios and small kinetic studies do not establish a universal optimal ratio.
How much Mg-dependent ROMK disinhibition explains potassium wasting in individual humans remains unquantified.Direct channel experiments used expressed channels or rodent tubules; human replacement/balance studies did not measure ROMK.
The link from plasma Mg to free intracellular Mg in the relevant distal cells remains unmeasured in the 2025 restriction experiment.The investigators explicitly did not measure distal-cell intracellular Mg; plasma hypomagnesemia is not an interchangeable compartment measurement.
The exact reason Mg restriction suppresses ENaC, and the quantitative role of distal sodium delivery, remain unresolved.No direct micropuncture measurement of delivery or thiazide response test established the full delivery mechanism.
Human PTH resistance during Mg deficiency is heterogeneous and does not have an established universal threshold.Small adult studies showed blunted responses, whereas a child retained renal and calcemic responses; duration, etiology and endpoint differ.
The contribution of CaSR/G-protein signaling versus other causes of impaired PTH release in human depletion remains unresolved.Cell/reconstitution probes support a mechanism but do not isolate it during human depletion.
A universal magnesium master gate or a rule that deficiency manifests only as failed nutrient replacement is not established.Selective human depletion altered physiology directly, and isolated Mg restriction in mice did not obligatorily produce potassium loss. These are scope limits, not a manufactured scientific conflict.
How often does documented hypomagnesemia cause clinically meaningful thiamine refractoriness?The retrieved human evidence is a three-patient report and a single later case, not a controlled estimate.
Which tissue Mg pool limits thiamine activation or ThDP-enzyme flux in a particular patient?Serum Mg, free cytosolic Mg, mitochondrial Mg, MgATP and enzyme-bound Mg are different quantities; the clinical reports did not measure this chain.
What fraction of native human TKT contains Mg versus Ca across tissues and nutritional states?Native erythrocyte metal analysis and Ca-loaded recombinant crystals support different preparation-specific observations, not a quantified in vivo replacement mechanism.
What is the precise TPK1 substrate-binding mechanism?Human steady-state kinetics supported ping-pong behavior whereas structural evidence is compatible with ternary complexes. The present module records the overall reaction without choosing an unproven intermediate.
Does reducing cellular Mg impair PDH/BCKDH primarily by ThDP binding, TPK1 activity, regulatory enzymes, or other pathways?The structural studies do not isolate these competing causes or establish magnesium-rescue efficacy.
Which Na/K-ATPase Mg-binding event becomes limiting during human Mg depletion?Binding order, ATP speciation and extra Mg sites differ across experimental states; purified enzyme data do not yield a serum threshold.
Native TRPM6/TRPM7 subunit composition and exact stoichiometry in each human epithelial segment remain unresolved by the cited heterologous experiments.Expression background and isoforms change apparent assembly requirements.
The relative intestinal versus renal contribution to human TRPM6 disease cannot be read directly from conditional mouse deletions.Species, developmental timing, diet and degree of recombination differ.
CNNM2 should not be encoded as a settled autonomous Mg channel or Na/Mg exchanger.Genetics establishes homeostatic importance, while negative transport assays and TRPM7 interaction demonstrate alternative regulatory explanations.
A uniquely Mg-selective claudin-16/19 pore is not established by this module.Tight-junction assembly, Na/Cl selectivity and Mg reabsorption are related but experimentally distinct. Reciprocal trafficking dependence is scoped to the RNAi models.
The MRS2 chloride-assisted permeation model is not equivalent to demonstrated obligatory Mg/Cl cotransport.Structure and simulations support a proposal; Arg332 substitutions did not materially change measured uptake in the cited mitochondrial assay.
The molecular cause of increased ectopy during low Mg intake is not isolated by the human feeding study.NMDA and CaV1.2 experiments cannot be inserted as a clinically proven causal chain to this cardiac endpoint.
Shared TRPM7 dependence of calcium, zinc and magnesium does not prove that low magnesium itself reduces zinc or calcium absorption.The intervention deleted a channel carrying several ions; an isolated nutrient perturbation was not used for that inference.
Generic claims that all DNA synthesis or all ribosomal protein synthesis fail at a defined human Mg threshold are intentionally absent.This module did not establish a precise primary enzyme-to-human nutritional threshold chain.

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

Evidence, AI assistance and curation standards

Magnesium

The mechanisms

Cytoplasmic Mg2+ caused voltage-dependent reduction of ROMK1 outward single-channel current without reducing channel open probability.

Lower external K+ increased the apparent affinity of cytoplasmic Mg2+ block of rat ROMK2 and permitted block over physiologically relevant negative voltages.

Mg2+ supplied through the whole-cell pipette reduced tertiapin-Q-sensitive current in rat cortical collecting-duct principal cells.

Extracellular Mg2+ also reduced ROMK2 single-channel current, with stronger apparent block as external K+ fell.

Mg restriction reduced cleaved alpha/gamma ENaC abundance and blunted amiloride-induced sodium excretion in mice.

Isolated Mg restriction produced hypomagnesemia without the hypokalemia observed under combined Na/Mg restriction in the tested mice.

Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet.

Plasma aldosterone in combined Na/Mg-restricted mice was not higher than with normal diet, although sodium restriction alone increased it.

The mouse findings support a model in which sustained ENaC sodium entry and higher ROMK conductance jointly favor potassium secretion during combined Na/Mg restriction.

Prolonged experimental Mg depletion caused hypokalemia requiring substantial extra potassium intake to maintain serum K, alongside decreased exchangeable potassium.

Serum potassium rose after Mg repletion in both men studied during prolonged experimental Mg depletion.

Randomized additional Mg sulfate improved 48-hour potassium input-minus-urine balance in hypokalemic ICU adults despite similar serum K; between-group total potassium replacement was not significantly different.

In bovine parathyroid slices, extracellular Mg and Ca inhibited PTH release additively, but Mg was less potent on a molar basis.

Mg concentration did not measurably change PTH biosynthesis or proPTH-to-PTH conversion in the bovine slice experiments.

In intact rat glands, raising Mg from 0.5 to 2 mM suppressed PTH most clearly at moderately low Ca; suppression was small or absent at normal-high Ca and diminished again at very low Ca.

At 1.0 mM Ca, six-hour exposure to 2.0 versus 0.5 mM Mg increased CaSR mRNA and protein in intact rat glands.

Most untreated patients in the clinical series had normal or undetectable immunoreactive PTH despite severe hypocalcemia.

Acute Mg administration increased circulating immunoreactive PTH within one minute in the three tested Mg-deficient patients.

During early Mg repletion, PTH recovered before serum calcium normalized in the serially studied patients.

Parathyroid extract produced only a small urinary cAMP response in the two Mg-deficient patients tested, while glucagon-stimulated plasma cAMP responses were preserved.

Mg administration promptly raised PTH in hypomagnesemic patients, whereas normal and hyperparathyroid comparison groups showed a decrease or little change.

After selective dietary Mg depletion, 20 of 26 adults showed unchanged or reduced PTH despite falling serum Mg and Ca.

Three weeks of selective Mg depletion produced a small but significant reduction in serum calcium in the adult study.

The rise in circulating calcitriol during a six-hour human PTH(1-34) infusion was smaller after dietary Mg depletion.

A child with primary hypomagnesemia retained calcemic and renal phosphate/cAMP responses to parathyroid extract during Mg depletion despite impaired endogenous PTH secretion.

Lowering extracellular Mg to 0.1 mM suppressed PTH release from dispersed human parathyroid cells in the tested media.

Low extracellular Mg increased inositol-phosphate generation in parathyroid cells; CaSR-expressing HEK-293 cells reproduced the enhancement.

Low Mg enhanced CaSR-associated inhibition of cAMP in the tested parathyroid and receptor-expression cell systems.

Pertussis-toxin pretreatment abolished the suppression of PTH release by low Mg in the parathyroid-cell assay.

Reconstituted G-protein assays supported Mg-dependent restraint of Galpha nucleotide exchange; reduced Mg enhanced signaling associated with basal CaSR activity.

The low-Mg enhancement of CaSR-stimulated GTP analogue binding was lost with the reduced-Mg-sensitivity Galpha-i1 R209C mutant; changing receptor extracellular cation affinity did not remove it.

Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+.

Mg2+ in excess over ATP restored human TPK1 activity at low MgATP concentrations compared with a 1:1 total Mg:ATP ratio.

Mouse TPK structures place Mg2+ adjacent to thiamine/ThDP and coordinated by active-site aspartate residues.

Recombinant mouse TPK1 showed an Mg optimum followed by inhibition as Mg was increased at fixed ATP.

Accumulated ThDP inhibited the forward reaction of purified mouse TPK1.

Sulfur-35-labeled ThDP binding was measured directly in human erythrocyte transketolase.

Native transketolase purified from human erythrocytes contained magnesium.

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

Human erythrocyte apo-transketolase activation kinetics supported slow Mg-ThDP binding followed by slow isomerization.

In recombinant human TKT, Ca2+ coordinates the ThDP diphosphate and protein ligands at the active site.

Recombinant human TKT retained ThDP and Ca2+ strongly under cofactor-removal conditions used in the study.

Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site.

The alphaV138M E1 structure displaced ThDP and disrupted the canonical Mg coordination site.

The human E1b coordinate model 1DTW contains two ThDP molecules and two Mg ions in its alpha2-beta2 assembly.

Human E1b contains potassium sites, including one organizing a loop near the ThDP cofactor.

The human OGDH cryo-EM model 7WGR contains Mg and ThDP as well as a separate Ca-binding site.

Mg increased purified pig-heart KGDHC activity only when ThDP was present in the assay.

Ca and Mg stimulation of purified pig-heart KGDHC was additive over the tested lower free-ion ranges.

The 2000 experiments interpreted MgADP as a more potent OGDHC activator than free ADP.

The 2000 study attributed ATP inhibition to Mg chelation and an inhibitory effect of MgATP.

A 2011 kinetic reanalysis favored independent Mg and ADP effects rather than requiring MgADP as the activating species.

In the 1974 report, blood transketolase recovered more slowly after thiamine in the hypomagnesemic patient than in two normomagnesemic patients.

Correcting hypomagnesemia in the 1974 patient coincided with clearing of ophthalmoplegia.

In the 2016 case, neurological symptoms resolved after intravenous Mg was added to ongoing thiamine for documented hypomagnesemia.

Pre-steady-state pig-kidney pump experiments identified Mg as an essential activator of ATP-dependent phosphorylation.

The 1992 best-fit model allowed free ATP or MgATP to bind before productive Mg-dependent phosphorylation.

Shark-pump kinetic fits assigned E1-ATP Mg affinity mainly to ATP coordination, after accounting for free ATP competition.

Adding KCl after ATP phosphorylation accelerated dephosphorylation of pig-kidney Na/K-ATPase.

In Mg-loaded human red-cell ghosts, ouabain-sensitive hydrolysis of one ATP accompanied loss of about three sodium ions.

Sodium-24 and potassium-42 experiments demonstrated ouabain-sensitive sodium efflux and potassium influx in human red cells.

Mg occupied cation transport site II in the ouabain-bound E2P pig-kidney pump structure.

Free Mg reduced apparent sodium affinity in pig-kidney pump sodium-22 occlusion experiments.

Recombinant TRPM6 expression generated Mg2+-permeable currents, supporting its participation in apical epithelial Mg entry.

TRPM6 coassembled with TRPM7 to form functional surface channel complexes in the tested expression systems.

TRPM6 S141L disrupted oligomeric assembly and functional TRPM6/TRPM7 complex formation.

Pathogenic biallelic TRPM6 variants were identified in families with hypomagnesemia and secondary hypocalcemia.

Intestine-restricted Trpm6 deletion reduced serum and bone magnesium in the tested adult mice.

Kidney-restricted Trpm6 deletion did not lower serum Mg or raise urinary Mg in the tested mice.

TRPM7-deficient DT40 cells became magnesium depleted.

Increasing extracellular Mg restored proliferation and viability of TRPM7-deficient DT40 cells.

Intestinal Trpm7 deletion lowered magnesium availability in early postnatal mice.

Intestinal Trpm7 deletion reduced serum and bone calcium in suckling mice.

Intestinal Trpm7 deletion reduced circulating zinc in early postnatal mice.

EGF increased TRPM6-associated current in transfected HEK293 cells through EGFR-dependent signaling.

Pro-EGF P1070L impaired basolateral delivery of TRPM6-stimulating EGF activity in polarized MDCK experiments.

Two homozygous EGF P1070L sisters had low serum magnesium with inappropriately sustained urinary Mg loss.

Human CLDN16 mutations were linked to renal magnesium wasting in the positional-cloning study.