Mg2+

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

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

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

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

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

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

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

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

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

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/

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Isolated membrane-vesicle cofactor-dependence experiments.

limitations

Cofactor removal is experimental machinery impairment, not proof that dietary magnesium deficiency changes human strontium retention by a specified amount.

nutrient_topic

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

plain_language

The pump needs both its energy source and magnesium.

primary_references

A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122

trigger_kind

machinery_impairment Imported condition classification; unverified.

Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 38–44

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated membrane-vesicle cofactor-dependence experiments. · source_derived_draft · unverified_draft

## strontium-renal-cofactor-loss The pump needs both its energy source and magnesium. Omission of ATP or magnesium prevented strontium uptake in the tested renal membrane preparation; other tested nucleotides did not substitute for ATP. Model: Isolated membrane-vesicle cofactor-dependence experiments. Limitations: Cofactor removal is experimental machinery impairment, not proof that dietary magnesium deficiency changes human strontium retention by a specified amount. Evidence access: Primary full text A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122

evidence_span

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experimental_model

Purified reconstructed COQ metabolon with short-chain substrates

exposure

Enzyme combinations, methyl donors, reductants and metal additions

limitations

Ancestral proteins and CoQ1 analogues; no clinical cofactor dose or proof of nutritional rate limitation. Reaction order need not be universal across species.

nutrient_topic

Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system

organism

Reconstructed ancestral tetrapod proteins

plain_language

Magnesium changed a specific methylation step in this biochemical system.

primary_references

[coq10-p38425362] In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. (2024). https://pubmed.ncbi.nlm.nih.gov/38425362/ DOI: 10.1038/s41929-023-01087-z

tissue_or_cell_type

Stepwise CoQ head-group assembly

Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 658–669

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified reconstructed COQ metabolon with short-chain substrates · source_derived_draft · unverified_draft

### coq10-coq3-magnesium Added magnesium increased reconstructed COQ3 activity about fourfold and improved substrate binding; EDTA abolished turnover. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium changed a specific methylation step in this biochemical system. organism: Reconstructed ancestral tetrapod proteins tissue_or_cell_type: Stepwise CoQ head-group assembly experimental_model: Purified reconstructed COQ metabolon with short-chain substrates limitations: Ancestral proteins and CoQ1 analogues; no clinical cofactor dose or proof of nutritional rate limitation. Reaction order need not be universal across species. exposure: Enzyme combinations, methyl donors, reductants and metal additions evidence_span: {"source_cache": "artifacts/coq10-research/38425362.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d25af4ecd7340649536b8fea3b8a0a308a1611bbf8c57f6a79b362f443f1cba", "start_char": 13814, "end_char": 15577, "text_sha256": "c43de1ac5dc6711fad8e37af3a52a8cd9784ed7eeaf77bd2981afe72abaf307f"} [coq10-p38425362] In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. (2024). https://pubmed.ncbi.nlm.nih.gov/38425362/ DOI: 10.1038/s41929-023-01087-z

evidence_access

Primary abstract

experimental_model

Human MAT2A structure with nonhydrolyzable imidotriphosphate and methylthioadenosine.

limitations

Inhibitor-bound structural contacts are not a dietary magnesium dose-response.

nutrient_topic

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

plain_language

SAM-making chemistry depends on correctly organized metal/phosphate contacts.

primary_references

Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 132–138

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MAT2A structure with nonhydrolyzable imidotriphosphate and methylthioadenosine. · source_derived_draft · unverified_draft

## methionine-mat-magnesium SAM-making chemistry depends on correctly organized metal/phosphate contacts. The human MAT2A inhibitor-bound structure contained two magnesium ions coordinating phosphate groups at the catalytic site. Model: Human MAT2A structure with nonhydrolyzable imidotriphosphate and methylthioadenosine. Limitations: Inhibitor-bound structural contacts are not a dietary magnesium dose-response. Evidence access: Primary abstract Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998

evidence_span

{"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"}

experimental_model

X-ray structure of a creatine kinase transition-state analogue complex

exposure

ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution

limitations

Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium.

nutrient_topic

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

organism

Torpedo californica enzyme

plain_language

Magnesium helps position the phosphate-transfer chemistry; creatine is only one component of that reaction.

primary_references

[creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

tissue_or_cell_type

Purified creatine kinase

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 347–358

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure of a creatine kinase transition-state analogue complex · source_derived_draft · unverified_draft

### creatine-ck-magnesium-complex Magnesium in the transition-state analogue complex coordinated ADP, nitrate and water ligands at the creatine kinase active site. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps position the phosphate-transfer chemistry; creatine is only one component of that reaction. organism: Torpedo californica enzyme tissue_or_cell_type: Purified creatine kinase experimental_model: X-ray structure of a creatine kinase transition-state analogue complex limitations: Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium. exposure: ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"} [creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

evidence_span

{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 1428, "end_char": 1604, "text_sha256": "a5d33b10162adea5e60fcff380eabf7e272963711914ea0e8e7091ad8c79df21"}

experimental_model

Human enzyme mutagenesis, kinetics and molecular dynamics

exposure

S-loop variants; established biosynthetic reactions described in the introduction

limitations

Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human GSS

plain_language

The induced glutathione pathway still depends on ordinary enzyme cofactors.

primary_references

[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

tissue_or_cell_type

Glutathione synthesis and substrate binding

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 866–877

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft

### sulforaphane-gss-magnesium The human GSS active sites bind ATP and associated magnesium for peptide-bond formation. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced glutathione pathway still depends on ordinary enzyme cofactors. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 1428, "end_char": 1604, "text_sha256": "a5d33b10162adea5e60fcff380eabf7e272963711914ea0e8e7091ad8c79df21"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

evidence_span

{"source_cache": "artifacts/k2-research/25874989.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbd73607ba2570aa383c81c189b29dd19f1cbd7bf7acdd8343ecf3ee7dc5faf8", "start_char": 45325, "end_char": 45633, "text_sha256": "6ae5b000cbc7fa6b682d2b2a915102061ea7bd2e3a3941a1bce8ed98ce0ee016"}

experimental_model

Microsomal enzyme assays and mutagenesis

exposure

Prenyl donors, reductant, magnesium and lipophilic statins

limitations

In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human UBIAD1 expressed in Sf9 insect cells

plain_language

More of a cofactor is not automatically better in an enzyme assay.

primary_references

[k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737

tissue_or_cell_type

Microsomal prenylation

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 227–238

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal enzyme assays and mutagenesis · source_derived_draft · unverified_draft

### k2-magnesium-context High added magnesium inhibited MK-4 synthesis with GGPP in the microsomal assay; residual microsomal magnesium prevented a zero-magnesium conclusion. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: More of a cofactor is not automatically better in an enzyme assay. organism: Human UBIAD1 expressed in Sf9 insect cells tissue_or_cell_type: Microsomal prenylation experimental_model: Microsomal enzyme assays and mutagenesis limitations: In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested. exposure: Prenyl donors, reductant, magnesium and lipophilic statins evidence_span: {"source_cache": "artifacts/k2-research/25874989.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbd73607ba2570aa383c81c189b29dd19f1cbd7bf7acdd8343ecf3ee7dc5faf8", "start_char": 45325, "end_char": 45633, "text_sha256": "6ae5b000cbc7fa6b682d2b2a915102061ea7bd2e3a3941a1bce8ed98ce0ee016"} [k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737

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

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

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

evidence_access

Primary abstract

experimental_model

Rat hippocampal patch-clamp experiment.

limitations

Does not establish that oral magnesium prevents quinolinate-related disease.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

Magnesium and membrane voltage changed the receptor response.

primary_references

Quinolinate activation of N-methyl-D-aspartate ion channels in rat hippocampal neurons. · 1990 · https://pubmed.ncbi.nlm.nih.gov/1700844/ · DOI 10.1016/0304-3940(90)90098-t

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 282–288

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat hippocampal patch-clamp experiment. · source_derived_draft · unverified_draft

## tryptophan-magnesium-nmda Magnesium and membrane voltage changed the receptor response. Adding 30 micromolar magnesium reduced quinolinate-activated NMDA channel mean open time to about one-third at minus 100 mV. Model: Rat hippocampal patch-clamp experiment. Limitations: Does not establish that oral magnesium prevents quinolinate-related disease. Evidence access: Primary abstract Quinolinate activation of N-methyl-D-aspartate ion channels in rat hippocampal neurons. · 1990 · https://pubmed.ncbi.nlm.nih.gov/1700844/ · DOI 10.1016/0304-3940(90)90098-t

evidence_access

Primary abstract

experimental_model

Human enzyme crystallography; the calcium-bound structure used 0.7 M CaCl2 crystallization conditions.

limitations

The high-calcium structure does not establish inhibition by normal dietary calcium.

nutrient_topic

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

plain_language

Two minerals can bind differently to the same enzyme.

primary_references

How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15291819/ · DOI 10.1111/j.0014-2956.2004.04277.x

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 54–60

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme crystallography; the calcium-bound structure used 0.7 M CaCl2 crystallization conditions. · source_derived_draft · unverified_draft

## l-serine-psph-metal Two minerals can bind differently to the same enzyme. Human PSPH uses an active-site Mg2+ ion; replacing it with Ca2+ changes coordination of catalytic Asp20 in a way that impedes nucleophilic attack. Model: Human enzyme crystallography; the calcium-bound structure used 0.7 M CaCl2 crystallization conditions. Limitations: The high-calcium structure does not establish inhibition by normal dietary calcium. Evidence access: Primary abstract How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15291819/ · DOI 10.1111/j.0014-2956.2004.04277.x

evidence_access

Primary full text

experimental_model

Human APE1 delta-N38; standard reaction initiated with 2 mM MgCl2.

limitations

Does not prove myricetin inhibits by magnesium chelation or causes magnesium deficiency.

nutrient_topic

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

plain_language

The repair enzyme also has a mineral-dependent assay requirement.

primary_references

Characterizing inhibitors of human AP endonuclease 1. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36652434/ · DOI 10.1371/journal.pone.0280526

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 676–682

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human APE1 delta-N38; standard reaction initiated with 2 mM MgCl2. · source_derived_draft · unverified_draft

## myricetin-ape1-magnesium The repair enzyme also has a mineral-dependent assay requirement. Omitting MgCl2 abolished detectable APE1 incision in the 2023 control reactions. Model: Human APE1 delta-N38; standard reaction initiated with 2 mM MgCl2. Limitations: Does not prove myricetin inhibits by magnesium chelation or causes magnesium deficiency. Evidence access: Primary full text Characterizing inhibitors of human AP endonuclease 1. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36652434/ · DOI 10.1371/journal.pone.0280526

evidence_access

Primary abstract

experimental_model

HRK1 patch-clamp comparison.

limitations

This is a gating comparison, not evidence that one nutrient replaces the other.

nutrient_topic

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

plain_language

Magnesium and spermidine influence the same channel with different kinetics.

primary_references

The mechanism of inward rectification of potassium channels: "long-pore plugging" by cytoplasmic polyamines. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8648298/ · DOI 10.1085/jgp.106.5.923

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 438–444

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HRK1 patch-clamp comparison. · source_derived_draft · unverified_draft

## spermidine-kir-magnesium Magnesium and spermidine influence the same channel with different kinetics. Magnesium-associated unblock was almost instantaneous, whereas spermidine unblock was time dependent. Model: HRK1 patch-clamp comparison. Limitations: This is a gating comparison, not evidence that one nutrient replaces the other. Evidence access: Primary abstract The mechanism of inward rectification of potassium channels: "long-pore plugging" by cytoplasmic polyamines. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8648298/ · DOI 10.1085/jgp.106.5.923

evidence_access

Primary abstract

experimental_model

Defined receptor assay solutions.

limitations

Voltage and ionic conditions are essential; no general claim that spermidine bypasses all NMDA magnesium block.

nutrient_topic

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

plain_language

A magnesium block is not identical for every permeating species.

primary_references

Spermidine and Ca(2+), but not Na(+), can permeate NMDA receptors consisting of GluN1 and GluN2A or GluN2B in the presence of Mg(2+). · 2015 · https://pubmed.ncbi.nlm.nih.gov/26086092/ · DOI 10.1016/j.bbrc.2015.06.081

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 470–476

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Defined receptor assay solutions. · source_derived_draft · unverified_draft

## spermidine-nmda-magnesium A magnesium block is not identical for every permeating species. Spermidine and calcium influx persisted under magnesium conditions that strongly inhibited sodium influx. Model: Defined receptor assay solutions. Limitations: Voltage and ionic conditions are essential; no general claim that spermidine bypasses all NMDA magnesium block. Evidence access: Primary abstract Spermidine and Ca(2+), but not Na(+), can permeate NMDA receptors consisting of GluN1 and GluN2A or GluN2B in the presence of Mg(2+). · 2015 · https://pubmed.ncbi.nlm.nih.gov/26086092/ · DOI 10.1016/j.bbrc.2015.06.081

evidence_access

Primary abstract

experimental_model

Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations.

limitations

Historical mechanistic model; not a universal count for all conformations or family members.

nutrient_topic

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

plain_language

Inositol recycling uses metal-dependent chemistry.

primary_references

Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 32–38

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations. · source_derived_draft · unverified_draft

## lithium-impa-metal Inositol recycling uses metal-dependent chemistry. Kinetics, modeling and mutagenesis supported a two-metal catalytic model for human inositol monophosphatase. Model: Human enzyme structural/kinetic study, including Mn, Zn and Mg titrations. Limitations: Historical mechanistic model; not a universal count for all conformations or family members. Evidence access: Primary abstract Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

evidence_access

Primary abstract

experimental_model

Calf-brain enzyme purification and kinetics.

limitations

In-vitro cofactor concentration is not a human blood target.

nutrient_topic

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

plain_language

A second recycling enzyme also depends on magnesium.

primary_references

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

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 48–54

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

## lithium-inpp1-magnesium A second recycling enzyme also depends on magnesium. Purified calf-brain INPP1 showed cooperative magnesium dependence, with half-maximal stimulation near 0.3 mM. Model: Calf-brain enzyme purification and kinetics. Limitations: In-vitro cofactor concentration is not a human blood target. Evidence access: Primary abstract Inositol polyphosphate 1-phosphatase from calf brain. Purification and inhibition by Li+, Ca2+, and Mn2+. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2824473/

cross_nutrient

Direct native-metal trapping distinguishes Mg occupancy from Mn-supported activity in vitro.

experimental_model

Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase

exposure

Methionine sulfoximine phosphate/ADP cofactor trapping

limitations

Extraction with methionine sulfoximine phosphate and ADP; bovine/ovine brain, not direct living human brain measurement.

nutrient_topic

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

organism

Bos taurus; Ovis aries

plain_language

A cofactor-trapping study recovered mainly magnesium from brain GLUL.

primary_references

[mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0

tissue_or_cell_type

Brain extracts and purified enzyme

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 646–657

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase · source_derived_draft · unverified_draft

### mn-enz-brain-glul-cofactor-trapping Cofactor-trapped GLUL from bovine or ovine brain contained 1.5±0.2 Mg per subunit and less than 0.05 Mn per subunit. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cofactor-trapping study recovered mainly magnesium from brain GLUL. organism: Bos taurus; Ovis aries tissue_or_cell_type: Brain extracts and purified enzyme experimental_model: Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase limitations: Extraction with methionine sulfoximine phosphate and ADP; bovine/ovine brain, not direct living human brain measurement. exposure: Methionine sulfoximine phosphate/ADP cofactor trapping cross_nutrient: Direct native-metal trapping distinguishes Mg occupancy from Mn-supported activity in vitro. [mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0

cross_nutrient

Competing primary interpretation of native GLUL Mn versus Mg identity.

experimental_model

Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase

exposure

Methionine sulfoximine phosphate/ADP cofactor trapping

limitations

Author interpretation of extracted enzyme; overlaps the ovine brain question in 1982, with different methods.

nutrient_topic

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

organism

Bos taurus; Ovis aries

plain_language

Another primary study supported magnesium as the native brain GLUL metal.

primary_references

[mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0

tissue_or_cell_type

Brain extracts and purified enzyme

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 659–670

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase · source_derived_draft · unverified_draft

### mn-enz-brain-glul-native-mg-interpretation The 1986 cofactor-trapping study concluded that Mg, rather than Mn, appears to be bound to bovine/ovine brain GLUL in vivo, although either metal supports assays. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Another primary study supported magnesium as the native brain GLUL metal. organism: Bos taurus; Ovis aries tissue_or_cell_type: Brain extracts and purified enzyme experimental_model: Cofactor trapping and immunoprecipitation of bovine and ovine brain glutamine synthetase limitations: Author interpretation of extracted enzyme; overlaps the ovine brain question in 1982, with different methods. exposure: Methionine sulfoximine phosphate/ADP cofactor trapping cross_nutrient: Competing primary interpretation of native GLUL Mn versus Mg identity. [mn-enz-2870682] Mg2+ is bound to glutamine synthetase extracted from bovine or ovine brain in the presence of L-methionine-S-sulfoximine phosphate. (1986). https://pubmed.ncbi.nlm.nih.gov/2870682/ DOI: 10.1016/0003-9861(86)90496-0

evidence_access

Primary abstract

experimental_model

Human wild-type inhibitor complex and R41M substrate complex.

limitations

Structural dependence does not show that dietary magnesium limits ketosis in a replete person.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

Magnesium participates directly in this ketone-producing enzyme.

primary_references

Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 120–126

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human wild-type inhibitor complex and R41M substrate complex. · source_derived_draft · unverified_draft

## fast-hmgcl-magnesium Magnesium participates directly in this ketone-producing enzyme. In HMGCL ternary structures Mg2+ coordinates His233, His235, Asp42, water and substrate/inhibitor oxygen atoms. Model: Human wild-type inhibitor complex and R41M substrate complex. Limitations: Structural dependence does not show that dietary magnesium limits ketosis in a replete person. Evidence access: Primary abstract Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931

evidence_span

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experimental_model

X-ray structures and human homology model

exposure

Glutamate/MgCl2 with or without ADP

limitations

Direct metal-site observation is yeast; the human model is an inference, not a human deficiency experiment.

nutrient_topic

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

organism

Saccharomyces cerevisiae enzyme; separate human model

plain_language

Magnesium has a role beyond merely being present in the assay buffer.

primary_references

[glutathione-p19726687] Mechanistic details of glutathione biosynthesis revealed by crystal structures of Saccharomyces cerevisiae glutamate cysteine ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19726687/ DOI: 10.1074/jbc.m109.025114

tissue_or_cell_type

Purified Gsh1

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 346–357

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures and human homology model · source_derived_draft · unverified_draft

### glutathione-gcl-magnesium The yeast GCL structures identified an ATP-independent magnesium coordination site associated with the enzyme’s Mg dependence. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium has a role beyond merely being present in the assay buffer. organism: Saccharomyces cerevisiae enzyme; separate human model tissue_or_cell_type: Purified Gsh1 experimental_model: X-ray structures and human homology model limitations: Direct metal-site observation is yeast; the human model is an inference, not a human deficiency experiment. exposure: Glutamate/MgCl2 with or without ADP evidence_span: {"source_cache": "artifacts/glutathione-research/19726687.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd125689fc03eaf0ec433fd6b967eecc6c52c234e99e3717f10218c2c4b97625", "start_char": 0, "end_char": 1461, "text_sha256": "fd125689fc03eaf0ec433fd6b967eecc6c52c234e99e3717f10218c2c4b97625"} [glutathione-p19726687] Mechanistic details of glutathione biosynthesis revealed by crystal structures of Saccharomyces cerevisiae glutamate cysteine ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19726687/ DOI: 10.1074/jbc.m109.025114

evidence_span

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experimental_model

Crystal structure and disease-variant mapping

exposure

ADP/GSH/sulfate-bound structure

limitations

Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim.

nutrient_topic

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

organism

Human enzyme

plain_language

The synthesis enzyme has a metal-containing nucleotide-binding environment.

primary_references

[glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204

tissue_or_cell_type

Purified GSS

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 333–344

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and disease-variant mapping · source_derived_draft · unverified_draft

### glutathione-gss-magnesium Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The synthesis enzyme has a metal-containing nucleotide-binding environment. organism: Human enzyme tissue_or_cell_type: Purified GSS experimental_model: Crystal structure and disease-variant mapping limitations: Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim. exposure: ADP/GSH/sulfate-bound structure evidence_span: {"source_cache": "artifacts/glutathione-research/10369661.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941", "start_char": 0, "end_char": 1327, "text_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941"} [glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204

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

evidence_span

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experimental_model

Purification and kinetics of placental PI synthase

exposure

Substrate and ion titrations

limitations

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

nutrient_topic

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

organism

Homo sapiens

plain_language

Magnesium can support the enzyme that builds PI.

primary_references

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

tissue_or_cell_type

Placental microsomal enzyme

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 509–520

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

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

evidence_span

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experimental_model

Site-directed mutagenesis and enzyme kinetics

exposure

Magnesium and lithium titrations

limitations

Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone.

nutrient_topic

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

organism

Human recombinant protein

plain_language

An enzyme can need a mineral yet become inhibited when its concentration is too high.

primary_references

[ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x

tissue_or_cell_type

Purified IMPA1

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 262–273

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis and enzyme kinetics · source_derived_draft · unverified_draft

### ino-impa-high-magnesium High Mg2+ concentrations inhibited human inositol monophosphatase uncompetitively with respect to substrate. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme can need a mineral yet become inhibited when its concentration is too high. organism: Human recombinant protein tissue_or_cell_type: Purified IMPA1 experimental_model: Site-directed mutagenesis and enzyme kinetics limitations: Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone. exposure: Magnesium and lithium titrations evidence_span: {"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"} [ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x

evidence_span

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experimental_model

Site-directed mutagenesis and enzyme kinetics

exposure

Magnesium and lithium titrations

limitations

Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone.

nutrient_topic

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

organism

Human recombinant protein

plain_language

Inositol recycling needs magnesium at the enzyme level.

primary_references

[ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x

tissue_or_cell_type

Purified IMPA1

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 249–260

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis and enzyme kinetics · source_derived_draft · unverified_draft

### ino-impa-magnesium Mg2+ was essential for human inositol monophosphatase activity. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inositol recycling needs magnesium at the enzyme level. organism: Human recombinant protein tissue_or_cell_type: Purified IMPA1 experimental_model: Site-directed mutagenesis and enzyme kinetics limitations: Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone. exposure: Magnesium and lithium titrations evidence_span: {"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"} [ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Perforated versus whole-cell patch clamp and FRET

exposure

PLC-coupled agonists with different intracellular magnesium conditions

limitations

The opposite current responses are explicitly explained by experimental ionic conditions; they are not an unresolved scientific contradiction.

nutrient_topic

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

organism

Mouse N1E-115 neuroblastoma cells

plain_language

Changing magnesium inside the recorded cell changed how the channel responded.

primary_references

[ino-p17095511] Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. (2007). https://pubmed.ncbi.nlm.nih.gov/17095511/ DOI: 10.1074/jbc.m605300200

tissue_or_cell_type

TRPM7-expressing cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 964–975

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perforated versus whole-cell patch clamp and FRET · source_derived_draft · unverified_draft

### ino-trpm7-low-mg PLC-dependent TRPM7 inhibition under whole-cell recording was observed only when intracellular Mg2+ was reduced below physiological levels. Condition category: nutrient_deficiency nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing magnesium inside the recorded cell changed how the channel responded. organism: Mouse N1E-115 neuroblastoma cells tissue_or_cell_type: TRPM7-expressing cells experimental_model: Perforated versus whole-cell patch clamp and FRET limitations: The opposite current responses are explicitly explained by experimental ionic conditions; they are not an unresolved scientific contradiction. exposure: PLC-coupled agonists with different intracellular magnesium conditions evidence_span: {"source_cache": "artifacts/inositol-research/17095511.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83", "start_char": 0, "end_char": 1403, "text_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83"} [ino-p17095511] Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. (2007). https://pubmed.ncbi.nlm.nih.gov/17095511/ DOI: 10.1074/jbc.m605300200

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

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

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

evidence_span

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experimental_model

Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography

exposure

ATP/methionine reactions and PNPNP ligand complexes

limitations

Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.

nutrient_topic

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

organism

Human recombinant enzyme

plain_language

Magnesium helped position the experimental phosphate-chain mimic at the enzyme site.

primary_references

[phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998

tissue_or_cell_type

Purified MAT2A active site

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 659–670

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft

### phosphorus-mat-magnesium Two Mg2+ ions chelated the alpha- and gamma-phosphoryl groups of PNPNP in the human MAT2A structure. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helped position the experimental phosphate-chain mimic at the enzyme site. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998

evidence_span

{"source_cache": "artifacts/chlorogenic_acid-research/3BWM.cif", "source_url": "https://files.rcsb.org/download/3BWM.cif", "locator": "Primary deposited structure 3BWM chemical-component loop; zero-based end-exclusive Unicode offsets", "file_sha256": "debe2736e6c5affecce595281fac469cd424ab6e91a5d908ec89d9460f60e4f6", "start_char": 11428, "end_char": 13476, "text_sha256": "98319e36f43f3fe147a2b9a2444809c31b0e14ae68e789fe3c1a8303fd8da8bc"}

experimental_model

Human soluble COMT crystallography and deposited structure 3BWM

exposure

SAM and 3,5-dinitrocatechol-bound crystals; deposited Mg ion

limitations

Structural cofactor connection, not a CGA-magnesium supplementation trial. Human and rat COMT specificity differs; deposition includes an inhibitor analog rather than CGA.

nutrient_topic

Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid

organism

Homo sapiens

plain_language

Magnesium is part of the measured enzyme complex; this does not prove that CGA depletes magnesium.

primary_references

[chlorogenic_acid-p18486144] Crystal structures of human 108V and 108M catechol O-methyltransferase. (2008). https://pubmed.ncbi.nlm.nih.gov/18486144/ DOI: 10.1016/j.jmb.2008.04.040

tissue_or_cell_type

Purified soluble COMT

Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 854–865

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human soluble COMT crystallography and deposited structure 3BWM · source_derived_draft · unverified_draft

### chlorogenic_acid-human-comt-mg The human COMT structure 3BWM includes bound magnesium alongside SAM and the catechol analog. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium is part of the measured enzyme complex; this does not prove that CGA depletes magnesium. organism: Homo sapiens tissue_or_cell_type: Purified soluble COMT experimental_model: Human soluble COMT crystallography and deposited structure 3BWM limitations: Structural cofactor connection, not a CGA-magnesium supplementation trial. Human and rat COMT specificity differs; deposition includes an inhibitor analog rather than CGA. exposure: SAM and 3,5-dinitrocatechol-bound crystals; deposited Mg ion evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/3BWM.cif", "source_url": "https://files.rcsb.org/download/3BWM.cif", "locator": "Primary deposited structure 3BWM chemical-component loop; zero-based end-exclusive Unicode offsets", "file_sha256": "debe2736e6c5affecce595281fac469cd424ab6e91a5d908ec89d9460f60e4f6", "start_char": 11428, "end_char": 13476, "text_sha256": "98319e36f43f3fe147a2b9a2444809c31b0e14ae68e789fe3c1a8303fd8da8bc"} [chlorogenic_acid-p18486144] Crystal structures of human 108V and 108M catechol O-methyltransferase. (2008). https://pubmed.ncbi.nlm.nih.gov/18486144/ DOI: 10.1016/j.jmb.2008.04.040

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

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

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

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

evidence_span

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experimental_model

Microsomal enzyme assays and mutagenesis

exposure

Prenyl donors, reductant, magnesium and lipophilic statins

limitations

In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human UBIAD1 expressed in Sf9 insect cells

plain_language

Magnesium-related enzyme chemistry is recorded separately from a claim that oral magnesium improves K2 status.

primary_references

[k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737

tissue_or_cell_type

Microsomal prenylation

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 214–225

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal enzyme assays and mutagenesis · source_derived_draft · unverified_draft

### k2-ubiad1-magnesium-site Mutational analysis assigned conserved domain IV to magnesium/isoprenyl-side-chain interactions. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium-related enzyme chemistry is recorded separately from a claim that oral magnesium improves K2 status. organism: Human UBIAD1 expressed in Sf9 insect cells tissue_or_cell_type: Microsomal prenylation experimental_model: Microsomal enzyme assays and mutagenesis limitations: In-vitro substrate and assay context. Residual microsomal magnesium prevents concluding that synthesis is magnesium-independent; no human supplementation effect was tested. exposure: Prenyl donors, reductant, magnesium and lipophilic statins evidence_span: {"source_cache": "artifacts/k2-research/25874989.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68", "start_char": 0, "end_char": 1777, "text_sha256": "a3eb5f4c56ca7a3e70a32c020bba09f4fec5e91048b13a188017bf221f713a68"} [k2-p25874989] Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. (2015). https://pubmed.ncbi.nlm.nih.gov/25874989/ DOI: 10.1371/journal.pone.0125737

evidence_access

Primary abstract

experimental_model

Purified human wild-type and variant PSPH; kinetic interpretation of physiological ion ranges.

limitations

This qualifies physiological extrapolation from binding assays; it does not deny the earlier calcium-bound structure.

nutrient_topic

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

plain_language

A required mineral need not be the rate-limiting input when its binding site is already occupied.

primary_references

Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 62–68

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human wild-type and variant PSPH; kinetic interpretation of physiological ion ranges. · source_derived_draft · unverified_draft

## l-serine-psph-physiology A required mineral need not be the rate-limiting input when its binding site is already occupied. The 2024 human PSPH study found near-saturation with Mg2+ under physiological conditions and judged ordinary Mg2+/Ca2+ fluctuations unlikely to regulate activity substantially. Model: Purified human wild-type and variant PSPH; kinetic interpretation of physiological ion ranges. Limitations: This qualifies physiological extrapolation from binding assays; it does not deny the earlier calcium-bound structure. Evidence access: Primary abstract Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

evidence_access

Primary full text

experimental_model

Isolated renal membrane vesicles; 90Sr and 45Ca tracers; ATP/Mg uptake assays.

limitations

Accessed methods refer to a prior preparation protocol without resolving species or ATP2B isoform. The assay measures ion transport, not radiation injury or net human renal clearance.

nutrient_topic

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

plain_language

A calcium-handling membrane preparation can also pump strontium.

primary_references

A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122

transport_effect

depends Membrane vesicles accumulated strontium in the assay, while the basolateral pump's role in the intact cell is extrusion toward blood; the two pools move opposite ways.

transport_pool

the proximal-tubule cell interior Membrane vesicles accumulated strontium in the assay, while the basolateral pump's role in the intact cell is extrusion toward blood; the two pools move opposite ways.

Strontium: calcium interactions, cellular mechanisms and mineralization (2026-09-19) · lines 14–20

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated renal membrane vesicles; 90Sr and 45Ca tracers; ATP/Mg uptake assays. · source_derived_draft · unverified_draft

## strontium-renal-uptake A calcium-handling membrane preparation can also pump strontium. Basolateral proximal-tubule membrane vesicles accumulated radiolabeled strontium in an ATP- and Mg2+-dependent transport assay. Model: Isolated renal membrane vesicles; 90Sr and 45Ca tracers; ATP/Mg uptake assays. Limitations: Accessed methods refer to a prior preparation protocol without resolving species or ATP2B isoform. The assay measures ion transport, not radiation injury or net human renal clearance. Evidence access: Primary full text A Comparison Between Calcium and Strontium Transport by the (Ca2+ + Mg2+)ATPase of the Basolateral Plasma Membrane of Renal Proximal Convoluted Tubules. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40277992/ · DOI 10.3390/membranes15040122

evidence_span

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experimental_model

Human choline kinase alpha1 and pathogen-enzyme biochemical comparison

exposure

ATP-dependent choline phosphorylation in magnesium-containing assays

limitations

The shared enzyme requirement is not a clinical magnesium threshold or proof of a general supplement rescue.

nutrient_topic

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

organism

Human alpha1 isoform; pathogen comparators remain separate

plain_language

Choline enters membrane synthesis through an ATP-powered phosphorylation step.

primary_references

[choline-p25515750] Choline kinase active site provides features for designing versatile inhibitors. (2014). https://pubmed.ncbi.nlm.nih.gov/25515750/ DOI: 10.2174/1568026614666141216093337

tissue_or_cell_type

Purified choline kinase active site

Choline: metabolism, signaling and nutrient connections (2026-09-17) · lines 698–709

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human choline kinase alpha1 and pathogen-enzyme biochemical comparison · source_derived_draft · unverified_draft

### choline-chka-phosphocholine Human choline kinase alpha1 catalyzes ATP-dependent phosphorylation of choline, producing phosphocholine and ADP in magnesium-containing conditions. Condition category: normal nutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Choline enters membrane synthesis through an ATP-powered phosphorylation step. organism: Human alpha1 isoform; pathogen comparators remain separate tissue_or_cell_type: Purified choline kinase active site experimental_model: Human choline kinase alpha1 and pathogen-enzyme biochemical comparison limitations: The shared enzyme requirement is not a clinical magnesium threshold or proof of a general supplement rescue. exposure: ATP-dependent choline phosphorylation in magnesium-containing assays evidence_span: {"source_cache": "artifacts/choline-research/25515750.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb", "start_char": 0, "end_char": 1321, "text_sha256": "742dc604629df5eae2bb6cfc0ef0a13cbd69f5e318a2f3292e98f2e707958aeb"} [choline-p25515750] Choline kinase active site provides features for designing versatile inhibitors. (2014). https://pubmed.ncbi.nlm.nih.gov/25515750/ DOI: 10.2174/1568026614666141216093337

evidence_access

Primary abstract

experimental_model

Rat liver F1 crystallography.

limitations

A captured structure is not proof that a given oral dose suppresses mitochondrial ATP production.

nutrient_topic

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

plain_language

Another ATP-handling enzyme can bind the phosphate analogue.

primary_references

Mitochondrial ATP synthase. Crystal structure of the catalytic F1 unit in a vanadate-induced transition-like state and implications for mechanism. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16531409/ · DOI 10.1074/jbc.M513369200

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 262–268

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat liver F1 crystallography. · source_derived_draft · unverified_draft

## vanadium-f1-transition Another ATP-handling enzyme can bind the phosphate analogue. Vanadate crystallization of rat-liver F1 ATP synthase captured an ADP–vanadate–Mg transition-like state with remodeling of the catalytic P-loop region. Model: Rat liver F1 crystallography. Limitations: A captured structure is not proof that a given oral dose suppresses mitochondrial ATP production. Evidence access: Primary abstract Mitochondrial ATP synthase. Crystal structure of the catalytic F1 unit in a vanadate-induced transition-like state and implications for mechanism. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16531409/ · DOI 10.1074/jbc.M513369200

evidence_access

Primary abstract

experimental_model

Dog kidney particulate-enzyme radiovanadate binding assay.

limitations

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

nutrient_topic

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

plain_language

The supporting divalent ion changed inhibitor affinity.

primary_references

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

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

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

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

evidence_access

Primary abstract

experimental_model

Dog kidney Na/K-ATPase binding experiments.

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

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

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

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

evidence_access

Primary abstract

experimental_model

Dog kidney enzyme binding assay.

limitations

No human dietary sodium recommendation follows.

nutrient_topic

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

plain_language

The ionic environment changes how vanadate interacts with the pump.

primary_references

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

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

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

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

evidence_access

Primary abstract and RCSB PDB 5A3Q author deposition

experimental_model

Rabbit SERCA structure, deposition 5A3Q; primary abstract plus author-deposited structure identity.

limitations

Structure used nucleotide analogues and thapsigargin; not a measured human intracellular calcium effect.

nutrient_topic

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

plain_language

A phosphate analogue can trap a calcium pump in a catalytic state.

primary_references

Crystal Structure of the Vanadate-Inhibited Ca(2+)-ATPase. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27050689/ · DOI 10.1016/j.str.2016.02.018

Vanadium: speciation, phosphate-sensitive enzymes and cross-nutrient mechanisms (2026-09-19) · lines 254–260

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rabbit SERCA structure, deposition 5A3Q; primary abstract plus author-deposited structure identity. · source_derived_draft · unverified_draft

## vanadium-serca-transition A phosphate analogue can trap a calcium pump in a catalytic state. Vanadate occupied the catalytic site of calcium-free SERCA as planar VO3 with water and magnesium in a dephosphorylation-transition-like conformation. Model: Rabbit SERCA structure, deposition 5A3Q; primary abstract plus author-deposited structure identity. Limitations: Structure used nucleotide analogues and thapsigargin; not a measured human intracellular calcium effect. Evidence access: Primary abstract and RCSB PDB 5A3Q author deposition Crystal Structure of the Vanadate-Inhibited Ca(2+)-ATPase. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27050689/ · DOI 10.1016/j.str.2016.02.018

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

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

evidence_span

{"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"}

experimental_model

X-ray structure of a creatine kinase transition-state analogue complex

exposure

ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution

limitations

Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium.

nutrient_topic

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

organism

Torpedo californica enzyme

plain_language

Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated.

primary_references

[creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

tissue_or_cell_type

Purified creatine kinase

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 334–345

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure of a creatine kinase transition-state analogue complex · source_derived_draft · unverified_draft

### creatine-ck-reversible-phosphate Creatine kinase catalyzes reversible phosphoryl transfer between ATP and creatine to form ADP and phosphocreatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated. organism: Torpedo californica enzyme tissue_or_cell_type: Purified creatine kinase experimental_model: X-ray structure of a creatine kinase transition-state analogue complex limitations: Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium. exposure: ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"} [creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p

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

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B1 shortage -> renal electrolyte handling in case evidence.

experimental_model

Two pediatric cases.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells.

primary_references

[b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019

tissue_or_cell_type

Kidney and blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1758–1769

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two pediatric cases. · source_derived_draft · unverified_draft

### b1-deficiency-renal-electrolyte-loss Two leukemia cases with acute thiamine deficiency showed proximal tubular dysfunction and electrolyte abnormalities resembling refeeding syndrome. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells. organism: Homo sapiens tissue_or_cell_type: Kidney and blood experimental_model: Two pediatric cases. limitations: The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here. cross_nutrient: B1 shortage -> renal electrolyte handling in case evidence. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019

evidence

[{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

1.9-A human DHTKD1 crystal structure.

limitations

Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand.

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

Homo sapiens

plain_language

DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable.

primary_references

[bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x

tissue_or_cell_type

Recombinant protein crystal

Thiamine: mechanisms, deficiency and nutrient interactions (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 · 1.9-A human DHTKD1 crystal structure. · source_derived_draft · unverified_draft

### b1-dhtkd1-thdp-dimer-sites The human DHTKD1 dimer structure places ThDP-containing active sites at the subunit interface and reveals a pocket compatible with the longer 2-oxoadipate substrate. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable. organism: Homo sapiens tissue_or_cell_type: Recombinant protein crystal experimental_model: 1.9-A human DHTKD1 crystal structure. limitations: Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand. evidence: [{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x

cross_nutrient

B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested.

evidence

[{"paper_key": "brizio-2006-fad", "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

Recombinant human FLAD1 isoforms expressed in E. coli.

limitations

No tissue Mg threshold or combined B1/B2 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

Homo sapiens

plain_language

The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes.

primary_references

[brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003

tissue_or_cell_type

Purified/expressed proteins

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 745–757

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human FLAD1 isoforms expressed in E. coli. · source_derived_draft · unverified_draft

### b1-fad-b2-cofactor-synthesis Recombinant human FLAD1 isoforms 1 and 2 exhibited FAD synthetase activity; isoform 2 was purified, and activity required MgCl2. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The flavin used by E3 must first be made from the riboflavin pathway. This distinct magnesium-dependent synthesis reaction should not be confused with magnesium binding to B1 enzymes. organism: Homo sapiens tissue_or_cell_type: Purified/expressed proteins experimental_model: Recombinant human FLAD1 isoforms expressed in E. coli. limitations: No tissue Mg threshold or combined B1/B2 deficiency experiment. evidence: [{"paper_key": "brizio-2006-fad", "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: B2 activation and Mg-dependent FAD synthesis provide a biochemical partner to B1-dependent complexes; direct transfer of newly made FAD to DLD was not tested. nutrient: Thiamine (vitamin B1) [brizio-2006-fad] Over-expression in Escherichia coli and characterization of two recombinant isoforms of human FAD synthetase (2006). https://pubmed.ncbi.nlm.nih.gov/16643857/ DOI: 10.1016/j.bbrc.2006.04.003

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

cross_nutrient

B1-dependent cleavage uses a B5-derived CoA-ester substrate.

evidence

[{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "generated fatty aldehyde", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human tagged HACL2 purified from HEK293T cells.

limitations

Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this 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

Homo sapiens

plain_language

B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA.

primary_references

[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114

tissue_or_cell_type

Purified membrane-associated protein

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1017–1029

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human tagged HACL2 purified from HEK293T cells. · source_derived_draft · unverified_draft

### b1-hacl2-thdp-dependent-coa-cleavage Affinity-purified human HACL2 produced fatty aldehyde from 2-hydroxy-C18:0-CoA, but not the free acid, and activity depended on added ThDP. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA. organism: Homo sapiens tissue_or_cell_type: Purified membrane-associated protein experimental_model: Human tagged HACL2 purified from HEK293T cells. limitations: Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this experiment. evidence: [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "generated fatty aldehyde", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent cleavage uses a B5-derived CoA-ester substrate. nutrient: Thiamine (vitamin B1) [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114

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

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

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B1 repletion and K/P/Mg management address different requirements.

experimental_model

Prospective cohort and individual case histories.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Providing vitamins did not by itself prevent every electrolyte and fluid complication.

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

Whole-body clinical nutrition

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1733–1744

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cohort and individual case histories. · source_derived_draft · unverified_draft

### b1-refeeding-vitamins-not-complete-rescue Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing vitamins did not by itself prevent every electrolyte and fluid complication. organism: Homo sapiens tissue_or_cell_type: Whole-body clinical nutrition experimental_model: Prospective cohort and individual case histories. limitations: No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency. cross_nutrient: B1 repletion and K/P/Mg management address different requirements. 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

cross_nutrient

Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP.

curation_note

Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection.

evidence-scope

Recombinant enzyme

evidence_locator

Abstract

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 His-tagged human TPK1; ATP/Mg kinetics and mutagenesis.

limitations

Overall chemistry does not resolve substrate-binding order.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step.

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

reaction

thiamine + ATP -> thiamine diphosphate + AMP

related_existing_claim_keys

["mg-tpk1-thiamine-to-thdp"]

tissue_or_cell_type

Recombinant enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 339–356

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-atp-amp-stoichiometry TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. limitations: Overall chemistry does not resolve substrate-binding order. cross_nutrient: Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP. reaction: thiamine + ATP -> thiamine diphosphate + AMP related_existing_claim_keys: ["mg-tpk1-thiamine-to-thdp"] curation_note: Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection. 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: 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

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

evidence_span

{"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"}

experimental_model

Phosphorylated CFTR channel nucleotide assays

exposure

Hydrolyzable nucleotides, analogues and Mg-free ATP

limitations

Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis.

nutrient_topic

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

organism

Human CFTR in expression preparations

plain_language

Magnesium and ATP are part of the working channel system; chloride alone is insufficient.

primary_references

[chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7

tissue_or_cell_type

Cytosolic channel face

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 250–261

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphorylated CFTR channel nucleotide assays · source_derived_draft · unverified_draft

### chloride-cftr-mgatp Phosphorylated CFTR channels opened with ATP but not Mg-free ATP in this preparation. Condition category: normal nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and ATP are part of the working channel system; chloride alone is insufficient. organism: Human CFTR in expression preparations tissue_or_cell_type: Cytosolic channel face experimental_model: Phosphorylated CFTR channel nucleotide assays limitations: Records the measured Mg/nucleotide dependence, not the paper’s historical assignment of opening to NBD1 hydrolysis. exposure: Hydrolyzable nucleotides, analogues and Mg-free ATP evidence_span: {"source_cache": "artifacts/chloride-research/1718606.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67", "start_char": 0, "end_char": 925, "text_sha256": "a66a28a6b6c5d2abfee4d416aeddca8f38a48e343d2715f599c8c05998943f67"} [chloride-p1718606] Nucleoside triphosphates are required to open the CFTR chloride channel. (1991). https://pubmed.ncbi.nlm.nih.gov/1718606/ DOI: 10.1016/0092-8674(91)90072-7

cross_nutrient

Potassium transport depends jointly on sodium and magnesium-supported ATP chemistry.

experimental_model

Resealed human erythrocyte ghosts; sided ion substitutions.

limitations

Sided activation adds to existing catalog flux/phosphorylation records; MgATP-only binding is not asserted.

nutrient_topic

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

organism

Human

plain_language

Potassium outside and sodium inside activate complementary sides of the pump.

primary_references

[garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocyte membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 575–585

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Resealed human erythrocyte ghosts; sided ion substitutions. · source_derived_draft · unverified_draft

### k-pump-extracellular-activation External potassium supported ouabain-sensitive ATP hydrolysis when erythrocyte ghosts contained sodium, ATP and magnesium. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium outside and sodium inside activate complementary sides of the pump. organism: Human tissue_or_cell_type: Erythrocyte membrane experimental_model: Resealed human erythrocyte ghosts; sided ion substitutions. limitations: Sided activation adds to existing catalog flux/phosphorylation records; MgATP-only binding is not asserted. cross_nutrient: Potassium transport depends jointly on sodium and magnesium-supported ATP chemistry. [garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

cross_nutrient

Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use.

experimental_model

Radiotracer sodium and ATP-hydrolysis assay.

limitations

This measurement does not itself establish an exact two-potassium ratio.

nutrient_topic

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

organism

Human

plain_language

ATP consumption pays for sodium extrusion while potassium is available externally.

primary_references

[garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

tissue_or_cell_type

Erythrocyte membrane

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 587–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer sodium and ATP-hydrolysis assay. · source_derived_draft · unverified_draft

### k-pump-sodium-atp-coupling Ouabain-sensitive extrusion was approximately three sodium ions per ATP hydrolyzed in resealed erythrocyte ghosts. Condition category: normal nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP consumption pays for sodium extrusion while potassium is available externally. organism: Human tissue_or_cell_type: Erythrocyte membrane experimental_model: Radiotracer sodium and ATP-hydrolysis assay. limitations: This measurement does not itself establish an exact two-potassium ratio. cross_nutrient: Sodium export couples to potassium-supported pump cycling and magnesium-dependent energy use. [garrahan-1967-pump] The stoicheiometry of the sodium pump (1967). https://pmc.ncbi.nlm.nih.gov/articles/PMC1365482/ DOI: 10.1113/jphysiol.1967.sp008297

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Small human case series, three adults with homozygous PCBD1 mutations.

limitations

Two also had MODY-like diabetes regardless of magnesium status; neither finding establishes that phenylalanine supplements cause or correct the disorder.

nutrient_topic

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

plain_language

A genetic defect can connect abnormal phenylalanine handling with magnesium wasting.

primary_references

Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24204001/ · DOI 10.1681/ASN.2013040337

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 94–100

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small human case series, three adults with homozygous PCBD1 mutations. · source_derived_draft · unverified_draft

## l-phenylalanine-pcbd-magnesium A genetic defect can connect abnormal phenylalanine handling with magnesium wasting. Two of three adults with homozygous PCBD1 mutations had hypomagnesemia with renal magnesium loss. Model: Small human case series, three adults with homozygous PCBD1 mutations. Limitations: Two also had MODY-like diabetes regardless of magnesium status; neither finding establishes that phenylalanine supplements cause or correct the disorder. Evidence access: Primary abstract Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24204001/ · DOI 10.1681/ASN.2013040337

evidence_access

Primary abstract

experimental_model

Human kidney-cell overexpression and promoter assay.

limitations

Promoter activity is not a direct measurement of magnesium flux or proof that phenylalanine intake regulates magnesium.

nutrient_topic

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

plain_language

A protein used in phenylalanine metabolism also helps control a kidney transport regulator.

primary_references

Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24204001/ · DOI 10.1681/ASN.2013040337

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 78–84

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human kidney-cell overexpression and promoter assay. · source_derived_draft · unverified_draft

## l-phenylalanine-pcbd-transcription A protein used in phenylalanine metabolism also helps control a kidney transport regulator. Overexpressed wild-type PCBD1 bound HNF1B and increased FXYD2 promoter activity in a human kidney cell line. Model: Human kidney-cell overexpression and promoter assay. Limitations: Promoter activity is not a direct measurement of magnesium flux or proof that phenylalanine intake regulates magnesium. Evidence access: Primary abstract Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24204001/ · DOI 10.1681/ASN.2013040337

evidence_access

Primary full text; Methods and structure

experimental_model

Chicken enzyme with bovine/porcine tubulin; 400 micromolar ATP, 2.4 millimolar MgCl2 and 5 micromolar labeled tyrosine in activity assays.

limitations

Mixed-species reconstitution is not a human supplementation experiment. This is retyrosination, not tyrosine phosphorylation.

nutrient_topic

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

plain_language

Tyrosine can be attached to an existing protein after translation.

primary_references

Structural basis of tubulin tyrosination by tubulin tyrosine ligase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23358242/ · DOI 10.1083/jcb.201211017

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 316–322

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chicken enzyme with bovine/porcine tubulin; 400 micromolar ATP, 2.4 millimolar MgCl2 and 5 micromolar labeled tyrosine in activity assays. · source_derived_draft · unverified_draft

## l-tyrosine-tubulin-retyrosination Tyrosine can be attached to an existing protein after translation. Recombinant chicken TTL incorporated radiolabeled tyrosine into mammalian brain alpha-tubulin in ATP/Mg-containing assays. Model: Chicken enzyme with bovine/porcine tubulin; 400 micromolar ATP, 2.4 millimolar MgCl2 and 5 micromolar labeled tyrosine in activity assays. Limitations: Mixed-species reconstitution is not a human supplementation experiment. This is retyrosination, not tyrosine phosphorylation. Evidence access: Primary full text; Methods and structure Structural basis of tubulin tyrosination by tubulin tyrosine ligase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23358242/ · DOI 10.1083/jcb.201211017

evidence_access

Primary abstract

experimental_model

Recombinant human PSPH functional analysis.

limitations

Free phosphoserine is distinct from a phosphorylated serine residue in a protein.

nutrient_topic

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

plain_language

The last enzyme releases free serine from its phosphorylated precursor.

primary_references

Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 46–52

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human PSPH functional analysis. · source_derived_draft · unverified_draft

## l-serine-psph-final-step The last enzyme releases free serine from its phosphorylated precursor. Human phosphoserine phosphatase catalyzes the final, effectively irreversible dephosphorylation step of the phosphorylated serine synthesis pathway. Model: Recombinant human PSPH functional analysis. Limitations: Free phosphoserine is distinct from a phosphorylated serine residue in a protein. Evidence access: Primary abstract Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034

cross_nutrient

true

experimental_model

Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution

exposure

Recombinant TNAP M4-site mutants and metal-dependent activity comparisons at pH 7.4 and 9.8.

limitations

This record states the authors’ mechanistic interpretation; existing M3 calcium substitution and Mg/Zn reconstitution claims remain unchanged. It does not imply dietary calcium is a zinc substitute.

nutrient_topic

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

organism

Homo sapiens

plain_language

TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural.

primary_references

[zinc-enz-tnap-metals2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase. (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874

tissue_or_cell_type

Purified protein; cell-free assay

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 820–831

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution · source_derived_draft · unverified_draft

### zinc-enz-tnap-m4-not-catalytic The recombinant TNAP mutant study attributed effects of disrupting calcium site M4 to protein structure rather than direct catalysis by M4-bound calcium. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural. organism: Homo sapiens tissue_or_cell_type: Purified protein; cell-free assay experimental_model: Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution limitations: This record states the authors’ mechanistic interpretation; existing M3 calcium substitution and Mg/Zn reconstitution claims remain unchanged. It does not imply dietary calcium is a zinc substitute. exposure: Recombinant TNAP M4-site mutants and metal-dependent activity comparisons at pH 7.4 and 9.8. cross_nutrient: true [zinc-enz-tnap-metals2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase. (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874

cross_nutrient

false

evidence_location

Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods

experimental_model

Purified human proteins

exposure

Crystallized complex with CoA, GDP and Mg2+

limitations

Static structure; does not directly measure the complete loading trajectory.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

The human-protein structure showed how MMAA opens access to MMUT-bound B12.

primary_references

[mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4

tissue_or_cell_type

Purified protein assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1117–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human proteins · source_derived_draft · unverified_draft

### mmaa-exposes-mmut-cobalamin-domain The human MMUT-MMAA structure showed MMAA stabilizing a roughly 180-degree rotation that exposed the MMUT B12-binding domain. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human-protein structure showed how MMAA opens access to MMUT-bound B12. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Static structure; does not directly measure the complete loading trajectory. exposure: Crystallized complex with CoA, GDP and Mg2+ cross_nutrient: false evidence_location: Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4

evidence_access

Primary abstract

experimental_model

Recombinant enzyme and cell-extract experiments; construct species not resolved in accessed abstract.

limitations

This is a shared-machinery connection, not a demonstrated magnesium effect on D-aspartate flux.

nutrient_topic

D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate

plain_language

Mineral and energy cofactors affect this enzyme, but the measured substrate was serine.

primary_references

Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12393813/ · DOI 10.1073/pnas.222421299

D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 64–70

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant enzyme and cell-extract experiments; construct species not resolved in accessed abstract. · source_derived_draft · unverified_draft

## d-aspartate-srr-mg-atp Mineral and energy cofactors affect this enzyme, but the measured substrate was serine. Mg2+ and ATP increased recombinant serine-racemase serine racemization and pyruvate production by approximately five- to ten-fold in the study assay. Model: Recombinant enzyme and cell-extract experiments; construct species not resolved in accessed abstract. Limitations: This is a shared-machinery connection, not a demonstrated magnesium effect on D-aspartate flux. Evidence access: Primary abstract Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12393813/ · DOI 10.1073/pnas.222421299

evidence_span

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experimental_model

Chemical modification and substrate protection of enzyme

exposure

Alpha-dicarbonyl modification with Mg-ATP protection

limitations

Protection assay identifies binding requirements; it is not a magnesium supplementation or depletion study.

nutrient_topic

Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline

organism

Human ASS1

plain_language

The active energy substrate is linked to magnesium, but more magnesium is not automatically rate-limiting.

primary_references

[citrulline-p2788888] Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase. (1989). https://pubmed.ncbi.nlm.nih.gov/2788888/

tissue_or_cell_type

ATP-binding region

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 164–175

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical modification and substrate protection of enzyme · source_derived_draft · unverified_draft

### citrulline-ass1-mg-atp Mg-ATP almost completely protected human ASS1 against alpha-dicarbonyl inactivation, implicating arginine residues in its binding site. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active energy substrate is linked to magnesium, but more magnesium is not automatically rate-limiting. organism: Human ASS1 tissue_or_cell_type: ATP-binding region experimental_model: Chemical modification and substrate protection of enzyme limitations: Protection assay identifies binding requirements; it is not a magnesium supplementation or depletion study. exposure: Alpha-dicarbonyl modification with Mg-ATP protection evidence_span: {"source_cache": "artifacts/citrulline-research/2788888.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29b1553359d37a53c529b8a2b53ba646cca6b4b401ba7a9722e0e1f15510e676", "start_char": 0, "end_char": 1043, "text_sha256": "29b1553359d37a53c529b8a2b53ba646cca6b4b401ba7a9722e0e1f15510e676"} [citrulline-p2788888] Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase. (1989). https://pubmed.ncbi.nlm.nih.gov/2788888/

cross_nutrient

Glutamine nitrogen handling and magnesium-containing ATP chemistry couple in a niacin precursor enzyme.

evidence_span

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experimental_model

Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate

exposure

Biochemical or structural assay; no dietary intervention

limitations

Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The two enzyme activities communicate while NAD is assembled.

primary_references

[b3-pre-nadsyn2019] Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases. (2020). https://pubmed.ncbi.nlm.nih.gov/31911602/ DOI: 10.1038/s41467-019-13845-4

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 342–354

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate · source_derived_draft · unverified_draft

### b3-pre-nadsyn-glutaminase Human NADSYN1 glutaminase activity was measured as glutamate production; NaAD plus ATP/Mg2+ increased that activity 31-fold over glutamine alone in the reported assay. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two enzyme activities communicate while NAD is assembled. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human NADSYN1 steady-state kinetic assays and crystallography; bacterial comparison kept separate limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention cross_nutrient: Glutamine nitrogen handling and magnesium-containing ATP chemistry couple in a niacin precursor enzyme. evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nadsyn2019.paragraphs.txt", "locator": "Normalized full-text paragraphs 10–10 (0-based)", "start_char": 8754, "end_char": 10450, "file_sha256": "36ad82ce734c8e0c44d01c7dc813b1641708738319b53a926e429155b1a602f4", "text_sha256": "32dd95b3bef542cb15f227e9dd3de1ed68b6b9c8f6cda41d34daf7b6fe387ce7"} [b3-pre-nadsyn2019] Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases. (2020). https://pubmed.ncbi.nlm.nih.gov/31911602/ DOI: 10.1038/s41467-019-13845-4

cross_nutrient

Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH.

evidence_span

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experimental_model

Full-length recombinant human NADK; G6PD-coupled assay

exposure

5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C

limitations

Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP.

primary_references

[nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664

tissue_or_cell_type

Purified enzyme

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 831–843

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Full-length recombinant human NADK; G6PD-coupled assay · source_derived_draft · unverified_draft

### b3-redox-nadk-mgatp Purified full-length human NADK catalyzed NADP+ production from NAD+ in a coupled assay supplied with 5 mM MgATP. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Full-length recombinant human NADK; G6PD-coupled assay limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: 5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C cross_nutrient: Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH. evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 53525, "end_char": 54577, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "db49fc47ad605562e1c1cf93e1b39596505906831ae509e7ec0031485f84ba4f"} [nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664

cross_nutrient

Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage.

evidence_span

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experimental_model

Purified His-tagged Δ62C5orf33/NADK2

exposure

TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°C

limitations

Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The mitochondrial kinase uses a phosphate-transfer reaction to create NADP+.

primary_references

[nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

tissue_or_cell_type

Purified protein

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 871–883

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged Δ62C5orf33/NADK2 · source_derived_draft · unverified_draft

### b3-redox-nadk2-phosphorylation Purified human NADK2 Δ62 converted NAD+ to NADP+ with ATP in MgCl2-containing reactions; TLC also detected ADP formation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial kinase uses a phosphate-transfer reaction to create NADP+. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Purified His-tagged Δ62C5orf33/NADK2 limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°C cross_nutrient: Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage. evidence_span: [{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 8475, "end_char": 9580, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "c86810a1a5342cd4e7ea126e070f28ed3182d81f17ea76c0fbb3833612c0f529"}, {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Methods, NADK activity assay", "start_char": 26694, "end_char": 28732, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "907b651f0c0aae7a31306bdc42264cdfd22fb0e236e7ab8f37900467b0b0ab72"}] [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

cross_nutrient

Uses phosphate polymers in a magnesium-containing enzyme assay, not a dietary phosphorus intervention.

evidence_span

{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 11596, "end_char": 12294, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "f371b72f3f7104e6b2b1f4f28ec55e04b18b931383b51a3258872db0809a10d9"}

experimental_model

Purified NADK2 Δ62

exposure

Metaphosphate, hexametaphosphate and tetrapolyphosphate tested

limitations

In vitro substrate capacity; physiological flux from polyphosphate in human mitochondria was not established. Monomeric phosphate is not interchangeable with these polymers.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

The recombinant mitochondrial enzyme accepted some polyphosphate preparations in vitro.

primary_references

[nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

tissue_or_cell_type

Purified enzyme

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 885–897

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified NADK2 Δ62 · source_derived_draft · unverified_draft

### b3-redox-nadk2-polyphosphate Purified human NADK2 Δ62 also supported NADP+ formation using inorganic polyphosphate preparations as phosphate donors. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The recombinant mitochondrial enzyme accepted some polyphosphate preparations in vitro. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Purified NADK2 Δ62 limitations: In vitro substrate capacity; physiological flux from polyphosphate in human mitochondria was not established. Monomeric phosphate is not interchangeable with these polymers. exposure: Metaphosphate, hexametaphosphate and tetrapolyphosphate tested cross_nutrient: Uses phosphate polymers in a magnesium-containing enzyme assay, not a dietary phosphorus intervention. evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 11596, "end_char": 12294, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "f371b72f3f7104e6b2b1f4f28ec55e04b18b931383b51a3258872db0809a10d9"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262

evidence_access

Primary abstract

experimental_model

Rat recombinant enzyme; calcium also inhibited activity.

limitations

Not a quantitative human exposure-to-organ-injury model.

nutrient_topic

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

plain_language

One lithium-sensitive enzyme connects two metabolic branches.

primary_references

A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 120–126

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat recombinant enzyme; calcium also inhibited activity. · source_derived_draft · unverified_draft

## lithium-bpnt1-lithium One lithium-sensitive enzyme connects two metabolic branches. Submillimolar lithium chloride inhibited rat RnPIP hydrolysis of both PAP and Ins(1,4)P2. Model: Rat recombinant enzyme; calcium also inhibited activity. Limitations: Not a quantitative human exposure-to-organ-injury model. Evidence access: Primary abstract A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

evidence_access

Primary abstract

experimental_model

Cloned rat enzyme; biochemical substrate assays.

limitations

The paper proposes consequences for sulfotransferases/RNA processing; those downstream effects were not all tested.

nutrient_topic

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

plain_language

Clearing a sulfur-pathway by-product uses another metal-dependent enzyme.

primary_references

A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 112–118

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cloned rat enzyme; biochemical substrate assays. · source_derived_draft · unverified_draft

## lithium-bpnt1-substrate Clearing a sulfur-pathway by-product uses another metal-dependent enzyme. Cloned rat RnPIP hydrolyzed PAP and Ins(1,4)P2 in magnesium-dependent reactions. Model: Cloned rat enzyme; biochemical substrate assays. Limitations: The paper proposes consequences for sulfotransferases/RNA processing; those downstream effects were not all tested. Evidence access: Primary abstract A novel mammalian lithium-sensitive enzyme with a dual enzymatic activity, 3'-phosphoadenosine 5'-phosphate phosphatase and inositol-polyphosphate 1-phosphatase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10347153/ · DOI 10.1074/jbc.274.23.16034

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse embryonic fibroblast pellets; complementation and sulfation assays.

limitations

Sulfation depends on compartment and substrate; not a universal human sulfur requirement.

nutrient_topic

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

plain_language

The enzyme must work, not merely be present.

primary_references

Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293

trigger_kind

machinery_impairment Imported condition classification; unverified.

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 152–158

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic fibroblast pellets; complementation and sulfation assays. · source_derived_draft · unverified_draft

## lithium-bpnt2-catalysis The enzyme must work, not merely be present. Wild-type Bpnt2 restored GAG sulfation in knockout fibroblasts; catalytic-dead D108A did not. Model: Mouse embryonic fibroblast pellets; complementation and sulfation assays. Limitations: Sulfation depends on compartment and substrate; not a universal human sulfur requirement. Evidence access: Primary full text Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34634304/ · DOI 10.1016/j.jbc.2021.101293

evidence_access

Primary abstract

experimental_model

Biochemical concentration titrations.

limitations

This is assay speciation, not evidence that lithium exhausts ATP or that extra magnesium improves clinical outcomes.

nutrient_topic

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

plain_language

ATP and free magnesium must be considered together.

primary_references

Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 24–30

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical concentration titrations. · source_derived_draft · unverified_draft

## lithium-gsk3-atp-magnesium ATP and free magnesium must be considered together. ATP concentrations exceeding magnesium progressively inhibited GSK3 in the assay through free-magnesium chelation. Model: Biochemical concentration titrations. Limitations: This is assay speciation, not evidence that lithium exhausts ATP or that extra magnesium improves clinical outcomes. Evidence access: Primary abstract Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

evidence_access

Primary abstract

experimental_model

Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms.

limitations

The abstract does not resolve every mammalian isoform; no systemic magnesium depletion was measured.

nutrient_topic

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

plain_language

Magnesium availability changes inhibition of a signaling enzyme.

primary_references

Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 16–22

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms. · source_derived_draft · unverified_draft

## lithium-gsk3-magnesium Magnesium availability changes inhibition of a signaling enzyme. Lithium competitively inhibited mammalian GSK3 with respect to magnesium, but not ATP or substrate. Model: Purified GSK3 kinetic experiments; mammalian and Dictyostelium isoforms. Limitations: The abstract does not resolve every mammalian isoform; no systemic magnesium depletion was measured. Evidence access: Primary abstract Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11162580/ · DOI 10.1006/bbrc.2000.4169

evidence_access

Primary abstract

experimental_model

Human enzyme kinetics, fluorescence and structural modeling.

limitations

Binding-site assignment is model-supported; treatment benefit is not established by enzyme inhibition.

nutrient_topic

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

plain_language

Lithium can interrupt the recycling step.

primary_references

Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19) · lines 40–46

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme kinetics, fluorescence and structural modeling. · source_derived_draft · unverified_draft

## lithium-impa-lithium Lithium can interrupt the recycling step. The human IMPase study supported lithium binding at the second metal site in its catalytic model. Model: Human enzyme kinetics, fluorescence and structural modeling. Limitations: Binding-site assignment is model-supported; treatment benefit is not established by enzyme inhibition. Evidence access: Primary abstract Mechanism of inositol monophosphatase, the putative target of lithium therapy. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8016062/ · DOI 10.1073/pnas.91.13.5766

cross_nutrient

Mn and Mg can support activity in vitro, with distinct metal:ATP ratios and pH conditions.

experimental_model

Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements

exposure

Mn(II) and Mg(II) titrations; binding and tissue metal measurements

limitations

Different assay optima are not evidence that Mn is the preferred cofactor at physiological brain pH.

nutrient_topic

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

organism

Ovis aries

plain_language

Magnesium and manganese supported GLUL under different assay conditions.

primary_references

[mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011

tissue_or_cell_type

Brain-derived purified enzyme

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 620–631

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements · source_derived_draft · unverified_draft

### mn-enz-ovine-glul-metal-kinetics Ovine brain GLUL assays showed optimal Mg:ATP at 2:1 and Mn:ATP at 1:1, with different reported pH optima of 7.5 and 5.0, respectively. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and manganese supported GLUL under different assay conditions. organism: Ovis aries tissue_or_cell_type: Brain-derived purified enzyme experimental_model: Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements limitations: Different assay optima are not evidence that Mn is the preferred cofactor at physiological brain pH. exposure: Mn(II) and Mg(II) titrations; binding and tissue metal measurements cross_nutrient: Mn and Mg can support activity in vitro, with distinct metal:ATP ratios and pH conditions. [mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011

cross_nutrient

Published inference about Mn versus Mg native occupancy; paired with the competing 1986 cofactor-trapping interpretation.

experimental_model

Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements

exposure

Mn(II) and Mg(II) titrations; binding and tissue metal measurements

limitations

Author inference; not a universal human GLUL cofactor assignment. Contradicted by a later overlapping ovine/bovine study using endogenous-cofactor trapping.

nutrient_topic

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

organism

Ovis aries

plain_language

One primary study proposed manganese as the native sheep-brain GLUL metal.

primary_references

[mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011

tissue_or_cell_type

Brain-derived purified enzyme

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 633–644

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements · source_derived_draft · unverified_draft

### mn-enz-ovine-glul-native-mn-interpretation From ovine-brain GLUL binding and tissue-metal measurements, the 1982 authors proposed that the enzyme may be manganese-bound in vivo. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: One primary study proposed manganese as the native sheep-brain GLUL metal. organism: Ovis aries tissue_or_cell_type: Brain-derived purified enzyme experimental_model: Ovine brain glutamine synthetase steady-state kinetics and metal-binding measurements limitations: Author inference; not a universal human GLUL cofactor assignment. Contradicted by a later overlapping ovine/bovine study using endogenous-cofactor trapping. exposure: Mn(II) and Mg(II) titrations; binding and tissue metal measurements cross_nutrient: Published inference about Mn versus Mg native occupancy; paired with the competing 1986 cofactor-trapping interpretation. [mn-enz-6129892] Glutamine synthetase from ovine brain is a manganese(II) enzyme. (1982). https://pubmed.ncbi.nlm.nih.gov/6129892/ DOI: 10.1021/bi00268a011

cross_nutrient

true

experimental_model

Purified full-length human SLC30A10 reconstituted into liposomes; Figure 1f and Supplementary Figure 3e-g

exposure

Separate MnCl2, ZnCl2, CaCl2 and MgCl2 proteoliposome transport tests.

limitations

The negative results are assay-bounded; they do not rule out calcium coupling under other gradients, establish exchange stoichiometry, or define a nutritional threshold.

nutrient_topic

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

organism

Human protein

plain_language

The purified transporter carried manganese without measurable transport of the three comparison metals in this assay.

primary_references

[mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7

tissue_or_cell_type

Proteoliposomes

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 396–407

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length human SLC30A10 reconstituted into liposomes; Figure 1f and Supplementary Figure 3e-g · source_derived_draft · unverified_draft

### mn-trans-slc30a10-metal-selectivity Reconstituted human SLC30A10 transported Mn(II), while the same study detected no significant Zn(II), Ca(II) or Mg(II) transport under its tested conditions. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The purified transporter carried manganese without measurable transport of the three comparison metals in this assay. organism: Human protein tissue_or_cell_type: Proteoliposomes experimental_model: Purified full-length human SLC30A10 reconstituted into liposomes; Figure 1f and Supplementary Figure 3e-g limitations: The negative results are assay-bounded; they do not rule out calcium coupling under other gradients, establish exchange stoichiometry, or define a nutritional threshold. exposure: Separate MnCl2, ZnCl2, CaCl2 and MgCl2 proteoliposome transport tests. cross_nutrient: true [mn-trans-41022720] Molecular mechanisms of SLC30A10-mediated manganese transport. (2025). https://pubmed.ncbi.nlm.nih.gov/41022720/ DOI: 10.1038/s41467-025-63616-7

experimental_model

Purified human COLGALT1 metal-substitution assays.

limitations

Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive.

organism

Human

plain_language

Manganese is a catalytic partner for this collagen-sugar enzyme.

primary_references

[colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 447–455

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human COLGALT1 metal-substitution assays. · source_derived_draft · unverified_draft

### manganese-colgalt1 Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay. Plain language: Manganese is a catalytic partner for this collagen-sugar enzyme. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified human COLGALT1 metal-substitution assays. limitations: Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive. [colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5

evidence_access

Primary abstract

experimental_model

17 adults; controlled diet; two 3 mg/kg lean-body-mass doses on day two of a before/after metabolic-ward trial.

limitations

Two-day urinary balance is not total body mineral balance or a long-term deficiency diagnosis.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

Later compensation reduced, but did not erase, the measured daily loss.

primary_references

Effect of caffeine on circadian excretion of urinary calcium and magnesium. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7836625/ · DOI 10.1080/07315724.1994.10718436

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 348–354

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · 17 adults; controlled diet; two 3 mg/kg lean-body-mass doses on day two of a before/after metabolic-ward trial. · source_derived_draft · unverified_draft

## caf-mg24 Later compensation reduced, but did not erase, the measured daily loss. Later nighttime conservation did not fully offset earlier loss; net 24-hour urinary excretion increased by 0.16 mmol. Model: 17 adults; controlled diet; two 3 mg/kg lean-body-mass doses on day two of a before/after metabolic-ward trial. Limitations: Two-day urinary balance is not total body mineral balance or a long-term deficiency diagnosis. Evidence access: Primary abstract Effect of caffeine on circadian excretion of urinary calcium and magnesium. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7836625/ · DOI 10.1080/07315724.1994.10718436

evidence_access

Primary abstract

experimental_model

37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection.

limitations

Acute renal handling. The exact tubular mechanism was unresolved; no long-term deficiency, bone loss or replacement requirement measured.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

The kidneys retained a smaller fraction of the filtered mineral.

primary_references

Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 292–298

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. · source_derived_draft · unverified_draft

## caf-renal-mg The kidneys retained a smaller fraction of the filtered mineral. Magnesium reabsorption fell from 97.0% to 94.2%, with no significant change in filtered magnesium load. Model: 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. Limitations: Acute renal handling. The exact tubular mechanism was unresolved; no long-term deficiency, bone loss or replacement requirement measured. Evidence access: Primary abstract Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y

evidence_access

Primary abstract

experimental_model

37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection.

limitations

Acute renal handling. The exact tubular mechanism was unresolved; no long-term deficiency, bone loss or replacement requirement measured.

nutrient_topic

Caffeine collection; salts, coffee, species and coexposure contexts retain their identities. · Caffeine

plain_language

The acute urine measurement increased.

primary_references

Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y

Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18) · lines 308–314

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. · source_derived_draft · unverified_draft

## caf-urine-mg The acute urine measurement increased. Urinary magnesium/creatinine rose from 70 to 110 mg/g. Model: 37 women, age 31–78; decaffeinated beverage with or without caffeine 6 mg/kg lean body mass; two-hour urine collection. Limitations: Acute renal handling. The exact tubular mechanism was unresolved; no long-term deficiency, bone loss or replacement requirement measured. Evidence access: Primary abstract Effects of dietary caffeine on renal handling of minerals in adult women. · 1990 · https://pubmed.ncbi.nlm.nih.gov/2402180/ · DOI 10.1016/0024-3205(90)90616-y

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

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

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