Nutrient chapter

L-Glutamate

Independent small molecule record; interpretation is limited by each linked claim and its study context.

82 recorded mechanisms · 9 availability situations · 13 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

In postabsorptive healthy adults, tracer comparisons estimated 96 ± 1% first-pass splanchnic extraction of enterally delivered glutamate.
Human first-pass splanchnic glutamate handling → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human crossover intravenous/nasogastric tracer infusion, 3.5 hours per route in each seven-hour study.
limitations
Splanchnic means gut plus liver region; the percentage is protocol-specific, not a fixed value for every meal or dose.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Much of an enteral tracer was handled before reaching the general circulation.
primary_references
Oxidation of glutamic acid by the splanchnic bed in humans. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7653544/ · DOI 10.1152/ajpendo.1995.269.2.E269
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 18–24
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human crossover intravenous/nasogastric tracer infusion, 3.5 hours per route in each seven-hour study. · source_derived_draft · unverified_draft
## glutamate-first-pass Much of an enteral tracer was handled before reaching the general circulation. In postabsorptive healthy adults, tracer comparisons estimated 96 ± 1% first-pass splanchnic extraction of enterally delivered glutamate. Model: Human crossover intravenous/nasogastric tracer infusion, 3.5 hours per route in each seven-hour study. Limitations: Splanchnic means gut plus liver region; the percentage is protocol-specific, not a fixed value for every meal or dose. Evidence access: Primary abstract Oxidation of glutamic acid by the splanchnic bed in humans. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7653544/ · DOI 10.1152/ajpendo.1995.269.2.E269
Complete structured claim and evidence
About 78 ± 3% of enterally delivered carbon-labeled glutamate tracer was recovered as exhaled CO2 in the study.
Human first-pass splanchnic glutamate handling → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human [1,2-13C2]glutamate tracer and breath CO2 measurements.
limitations
Whole-body breath recovery does not identify the cell type oxidizing each molecule.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Glutamate carbon was used as fuel, not merely redistributed as amino nitrogen.
primary_references
Oxidation of glutamic acid by the splanchnic bed in humans. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7653544/ · DOI 10.1152/ajpendo.1995.269.2.E269
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 26–32
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human [1,2-13C2]glutamate tracer and breath CO2 measurements. · source_derived_draft · unverified_draft
## glutamate-first-pass-oxidation Glutamate carbon was used as fuel, not merely redistributed as amino nitrogen. About 78 ± 3% of enterally delivered carbon-labeled glutamate tracer was recovered as exhaled CO2 in the study. Model: Human [1,2-13C2]glutamate tracer and breath CO2 measurements. Limitations: Whole-body breath recovery does not identify the cell type oxidizing each molecule. Evidence access: Primary abstract Oxidation of glutamic acid by the splanchnic bed in humans. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7653544/ · DOI 10.1152/ajpendo.1995.269.2.E269
Complete structured claim and evidence
After six fasted adults ingested 100 mg nitrogen-labeled L-glutamic acid, most recovered circulating amino-acid label appeared in alanine and glutamine, with no significant amino-acid concentration changes during 150 minutes.
L-Glutamate → Human arterial alanine/glutamine nitrogen labeling source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human oral 15N tracer, arterialized blood sampling for 150 minutes.
limitations
Small tracer experiment; it does not establish supplement efficacy or a universal conversion fraction.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
The incoming amino nitrogen could leave the gut region in different molecules.
primary_references
Measurement of the transfer of the nitrogen moiety of intestinal lumen glutamic acid in man after oral ingestion of l-[15N]glutamic acid. · 1988 · https://pubmed.ncbi.nlm.nih.gov/2908193/ · DOI 10.1042/cs0750499
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 34–40
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human oral 15N tracer, arterialized blood sampling for 150 minutes. · source_derived_draft · unverified_draft
## glutamate-dietary-nitrogen The incoming amino nitrogen could leave the gut region in different molecules. After six fasted adults ingested 100 mg nitrogen-labeled L-glutamic acid, most recovered circulating amino-acid label appeared in alanine and glutamine, with no significant amino-acid concentration changes during 150 minutes. Model: Human oral 15N tracer, arterialized blood sampling for 150 minutes. Limitations: Small tracer experiment; it does not establish supplement efficacy or a universal conversion fraction. Evidence access: Primary abstract Measurement of the transfer of the nitrogen moiety of intestinal lumen glutamic acid in man after oral ingestion of l-[15N]glutamic acid. · 1988 · https://pubmed.ncbi.nlm.nih.gov/2908193/ · DOI 10.1042/cs0750499
Complete structured claim and evidence
Coexpressed human T1R1/T1R3 responded to L-glutamate in receptor assays.
L-Glutamate → Human umami receptor TAS1R1/TAS1R3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Heterologous expression of human taste receptors.
limitations
Taste-receptor activation does not establish a brain neurotransmitter effect.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Two receptor proteins recognize the umami signal.
primary_references
Human receptors for sweet and umami taste. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11917125/ · DOI 10.1073/pnas.072090199
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 42–48
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Heterologous expression of human taste receptors. · source_derived_draft · unverified_draft
## glutamate-umami-receptor Two receptor proteins recognize the umami signal. Coexpressed human T1R1/T1R3 responded to L-glutamate in receptor assays. Model: Heterologous expression of human taste receptors. Limitations: Taste-receptor activation does not establish a brain neurotransmitter effect. Evidence access: Primary abstract Human receptors for sweet and umami taste. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11917125/ · DOI 10.1073/pnas.072090199
Complete structured claim and evidence
5-prime-ribonucleotides enhanced the human T1R1/T1R3 response to L-glutamate.
Inosine 5-prime-monophosphate / IMP → Human umami receptor TAS1R1/TAS1R3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human receptor coexpression and ligand-response assays.
limitations
A measured receptor interaction, not a general metabolic or clinical synergy.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A nucleotide can enhance the response to an amino acid at a receptor.
primary_references
Human receptors for sweet and umami taste. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11917125/ · DOI 10.1073/pnas.072090199
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 50–56
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human receptor coexpression and ligand-response assays. · source_derived_draft · unverified_draft
## glutamate-umami-nucleotide A nucleotide can enhance the response to an amino acid at a receptor. 5-prime-ribonucleotides enhanced the human T1R1/T1R3 response to L-glutamate. Model: Human receptor coexpression and ligand-response assays. Limitations: A measured receptor interaction, not a general metabolic or clinical synergy. Evidence access: Primary abstract Human receptors for sweet and umami taste. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11917125/ · DOI 10.1073/pnas.072090199
Complete structured claim and evidence
Human/mouse receptor chimeras and point mutants mapped acidic-amino-acid selectivity to the T1R1 ligand-binding region and identified other residues that broadened mouse-type responses.
Human taste receptor TAS1R1 → Human umami receptor TAS1R1/TAS1R3 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human/mouse receptor chimeras and mutagenesis.
limitations
Sequence-dependent selectivity is not evidence that all mammalian umami receptors behave identically.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
The species of the receptor changes what the same ligand experiment means.
primary_references
Two distinct determinants of ligand specificity in T1R1/T1R3 (the umami taste receptor). · 2013 · https://pubmed.ncbi.nlm.nih.gov/24214976/ · DOI 10.1074/jbc.M113.494443
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 58–64
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human/mouse receptor chimeras and mutagenesis. · source_derived_draft · unverified_draft
## glutamate-umami-species The species of the receptor changes what the same ligand experiment means. Human/mouse receptor chimeras and point mutants mapped acidic-amino-acid selectivity to the T1R1 ligand-binding region and identified other residues that broadened mouse-type responses. Model: Human/mouse receptor chimeras and mutagenesis. Limitations: Sequence-dependent selectivity is not evidence that all mammalian umami receptors behave identically. Evidence access: Primary full text Two distinct determinants of ligand specificity in T1R1/T1R3 (the umami taste receptor). · 2013 · https://pubmed.ncbi.nlm.nih.gov/24214976/ · DOI 10.1074/jbc.M113.494443
Complete structured claim and evidence
Intragastric 150 mM MSG increased gastric vagal afferent discharge in anesthetized rats.
Monosodium L-glutamate → Rat gastric vagal afferent activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Anesthetized rats; 2 mL intragastric infusion at 1 mL/min, nerve discharge assessed after infusion.
limitations
MSG was the exposure; human food intake and subjective effects were not tested.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Glutamate in the stomach can signal through nerves without first acting at a brain glutamate receptor.
primary_references
Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21132420/ · DOI 10.1007/s12576-010-0121-z
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 66–72
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Anesthetized rats; 2 mL intragastric infusion at 1 mL/min, nerve discharge assessed after infusion. · source_derived_draft · unverified_draft
## glutamate-gastric-vagal Glutamate in the stomach can signal through nerves without first acting at a brain glutamate receptor. Intragastric 150 mM MSG increased gastric vagal afferent discharge in anesthetized rats. Model: Anesthetized rats; 2 mL intragastric infusion at 1 mL/min, nerve discharge assessed after infusion. Limitations: MSG was the exposure; human food intake and subjective effects were not tested. Evidence access: Primary full text Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21132420/ · DOI 10.1007/s12576-010-0121-z
Complete structured claim and evidence
MSG-evoked celiac vagal and adrenal splanchnic efferent responses were abolished by gastric vagotomy in rats.
Rat gastric vagal afferent activity → Rat gastric glutamate-evoked autonomic reflex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Anesthetized-rat intragastric infusion with gastric-branch vagotomy.
limitations
Nerve discharge is not direct measurement of a human hormonal or health benefit.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Cutting the sensory route interrupted the downstream reflex.
primary_references
Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21132420/ · DOI 10.1007/s12576-010-0121-z
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 74–80
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Anesthetized-rat intragastric infusion with gastric-branch vagotomy. · source_derived_draft · unverified_draft
## glutamate-gastric-reflex Cutting the sensory route interrupted the downstream reflex. MSG-evoked celiac vagal and adrenal splanchnic efferent responses were abolished by gastric vagotomy in rats. Model: Anesthetized-rat intragastric infusion with gastric-branch vagotomy. Limitations: Nerve discharge is not direct measurement of a human hormonal or health benefit. Evidence access: Primary full text Effects of intragastric infusion of inosine monophosphate and L: -glutamate on vagal gastric afferent activity and subsequent autonomic reflexes. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21132420/ · DOI 10.1007/s12576-010-0121-z
Complete structured claim and evidence
Reconstituted human glutamate carrier 1 supported glutamate transport coupled to a proton gradient.
Human mitochondrial glutamate carrier 1 / SLC25A22 → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human carrier expressed in E. coli and reconstituted in phospholipid vesicles.
limitations
Glutamate/H+ cotransport and glutamate/OH− exchange are alternative descriptions in this assay; this is not the aspartate/glutamate exchanger.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Cytosolic glutamate needs a carrier to reach mitochondrial reactions.
primary_references
Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11897791/ · DOI 10.1074/jbc.M201572200
transport_effect
depends The record names the proton coupling and not which way glutamate crossed the membrane.
transport_pool
the mitochondrial matrix The record names the proton coupling and not which way glutamate crossed the membrane.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 82–88
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human carrier expressed in E. coli and reconstituted in phospholipid vesicles. · source_derived_draft · unverified_draft
## glutamate-mitochondrial-gc1 Cytosolic glutamate needs a carrier to reach mitochondrial reactions. Reconstituted human glutamate carrier 1 supported glutamate transport coupled to a proton gradient. Model: Human carrier expressed in E. coli and reconstituted in phospholipid vesicles. Limitations: Glutamate/H+ cotransport and glutamate/OH− exchange are alternative descriptions in this assay; this is not the aspartate/glutamate exchanger. Evidence access: Primary abstract Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11897791/ · DOI 10.1074/jbc.M201572200
Complete structured claim and evidence
Reconstituted human glutamate carrier 2 also supported glutamate/proton-coupled transport, with kinetic and expression differences from carrier 1.
Human mitochondrial glutamate carrier 2 / SLC25A18 → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human SLC25A18 compared with SLC25A22 in vesicle transport assays.
limitations
The proposed allocation to basal versus high-demand metabolism was an interpretation, not a universal tissue ranking.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A related carrier is a separate node with its own properties.
primary_references
Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11897791/ · DOI 10.1074/jbc.M201572200
transport_effect
depends The record names the proton coupling and not which way glutamate crossed the membrane.
transport_pool
the mitochondrial matrix The record names the proton coupling and not which way glutamate crossed the membrane.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 90–96
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human SLC25A18 compared with SLC25A22 in vesicle transport assays. · source_derived_draft · unverified_draft
## glutamate-mitochondrial-gc2 A related carrier is a separate node with its own properties. Reconstituted human glutamate carrier 2 also supported glutamate/proton-coupled transport, with kinetic and expression differences from carrier 1. Model: Recombinant human SLC25A18 compared with SLC25A22 in vesicle transport assays. Limitations: The proposed allocation to basal versus high-demand metabolism was an interpretation, not a universal tissue ranking. Evidence access: Primary abstract Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization, and tissue distribution of two human isoforms. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11897791/ · DOI 10.1074/jbc.M201572200
Complete structured claim and evidence
The homozygous SLC25A22 p.G236W variant identified in a child with severe neonatal epileptic encephalopathy abolished carrier activity in vitro.
Human SLC25A22 p.G236W variant → Human mitochondrial glutamate carrier 1 / SLC25A22 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human genetic case and recombinant transport assay.
limitations
A carrier disorder does not establish dietary glutamate deficiency or successful rescue by oral glutamate.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Enough amino acid outside mitochondria cannot guarantee transport through defective machinery.
primary_references
Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19780765/ · DOI 10.1111/j.1399-0004.2009.01236.x
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 98–104
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human genetic case and recombinant transport assay. · source_derived_draft · unverified_draft
## glutamate-gc1-variant Enough amino acid outside mitochondria cannot guarantee transport through defective machinery. The homozygous SLC25A22 p.G236W variant identified in a child with severe neonatal epileptic encephalopathy abolished carrier activity in vitro. Model: Human genetic case and recombinant transport assay. Limitations: A carrier disorder does not establish dietary glutamate deficiency or successful rescue by oral glutamate. Evidence access: Primary abstract Mutations in the mitochondrial glutamate carrier SLC25A22 in neonatal epileptic encephalopathy with suppression bursts. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19780765/ · DOI 10.1111/j.1399-0004.2009.01236.x
Complete structured claim and evidence
Bovine brain-capillary membrane preparations contained EAAT1/2/3 on the abluminal side and showed voltage- and potassium-dependent glutamate uptake.
Bovine blood-brain-barrier EAAT1/EAAT2/EAAT3 transporter panel → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV.
limitations
The panel is not a physical three-protein complex; transport assays do not measure whole human brain exposure after food intake.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
The brain-facing barrier membrane participates in removing extracellular glutamate.
primary_references
Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10542215/ · DOI 10.1074/jbc.274.45.31891
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 106–112
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV. · source_derived_draft · unverified_draft
## glutamate-bbb-clearance The brain-facing barrier membrane participates in removing extracellular glutamate. Bovine brain-capillary membrane preparations contained EAAT1/2/3 on the abluminal side and showed voltage- and potassium-dependent glutamate uptake. Model: Bovine capillary RNA, membrane protein analysis and transport kinetics; aggregate apparent Km 14 micromolar at −61 mV. Limitations: The panel is not a physical three-protein complex; transport assays do not measure whole human brain exposure after food intake. Evidence access: Primary abstract Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10542215/ · DOI 10.1074/jbc.274.45.31891
Complete structured claim and evidence
Homozygous Slc1a2/GLT-1 deletion in mice caused lethal spontaneous seizures and increased susceptibility to cortical injury, with elevated residual glutamate.
Mouse glutamate transporter GLT-1 / Slc1a2 → Seizures and cortical-injury susceptibility in mouse GLT-1 deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse whole-body transporter knockout and acute cortical injury.
limitations
Developmental gene deletion is not ordinary variation in dietary glutamate.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Failure to clear a transmitter can be harmful even though the molecule is normally essential.
primary_references
Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9180080/ · DOI 10.1126/science.276.5319.1699
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 114–120
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse whole-body transporter knockout and acute cortical injury. · source_derived_draft · unverified_draft
## glutamate-glt1-deletion Failure to clear a transmitter can be harmful even though the molecule is normally essential. Homozygous Slc1a2/GLT-1 deletion in mice caused lethal spontaneous seizures and increased susceptibility to cortical injury, with elevated residual glutamate. Model: Mouse whole-body transporter knockout and acute cortical injury. Limitations: Developmental gene deletion is not ordinary variation in dietary glutamate. Evidence access: Primary abstract Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9180080/ · DOI 10.1126/science.276.5319.1699
Complete structured claim and evidence
Two infants with homozygous GLUL mutations had profoundly low glutamine and severe neonatal disease; variant expression assays showed reduced enzyme activity.
Human GLUL R324C/R341C deficiency → Glutamine synthetase / GLUL source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells.
limitations
This is congenital glutamine-synthesis failure, not evidence of inadequate dietary glutamate.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A synthesis defect can prevent conversion of one available amino acid into another.
primary_references
Congenital glutamine deficiency with glutamine synthetase mutations. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16267323/ · DOI 10.1056/NEJMoa050456
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 122–128
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells. · source_derived_draft · unverified_draft
## glutamate-glul-human-loss A synthesis defect can prevent conversion of one available amino acid into another. Two infants with homozygous GLUL mutations had profoundly low glutamine and severe neonatal disease; variant expression assays showed reduced enzyme activity. Model: Two unrelated newborns, patient lymphocytes and mutant expression in COS7 cells. Limitations: This is congenital glutamine-synthesis failure, not evidence of inadequate dietary glutamate. Evidence access: Primary abstract Congenital glutamine deficiency with glutamine synthetase mutations. · 2005 · https://pubmed.ncbi.nlm.nih.gov/16267323/ · DOI 10.1056/NEJMoa050456
Complete structured claim and evidence
Repeated high-frequency stimulation of rat hippocampal and cortical terminals reduced synaptic efficacy and glutamate release; the effect depended on activity pattern.
Repetitive stimulation of isolated rat axon terminals → Rat hippocampal local glutamate supply for release source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat brain slices with axons transected; alternating 20 Hz and 0.2 Hz stimulation and naturalistic patterns.
limitations
This is a local experimental supply limitation, not a dietary glutamate-deficiency threshold.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A local transmitter supply can become insufficient when demand rises.
primary_references
A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 130–136
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat brain slices with axons transected; alternating 20 Hz and 0.2 Hz stimulation and naturalistic patterns. · source_derived_draft · unverified_draft
## glutamate-recycling-demand A local transmitter supply can become insufficient when demand rises. Repeated high-frequency stimulation of rat hippocampal and cortical terminals reduced synaptic efficacy and glutamate release; the effect depended on activity pattern. Model: Rat brain slices with axons transected; alternating 20 Hz and 0.2 Hz stimulation and naturalistic patterns. Limitations: This is a local experimental supply limitation, not a dietary glutamate-deficiency threshold. Evidence access: Primary full text A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
Complete structured claim and evidence
Blocking glutamine synthetase with methionine sulfoximine worsened activity-dependent synaptic depression in rat hippocampal slices.
Methionine sulfoximine → Rat glutamine synthetase / Glul source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Rat slice glutamine-synthetase inhibition and evoked field-potential recordings.
limitations
The inhibitor also restricts newly synthesized glutamine; recycling is not the only possible affected source.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Disabling the recycling enzyme made the local supply problem worse.
primary_references
A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 138–144
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat slice glutamine-synthetase inhibition and evoked field-potential recordings. · source_derived_draft · unverified_draft
## glutamate-recycling-gs-block Disabling the recycling enzyme made the local supply problem worse. Blocking glutamine synthetase with methionine sulfoximine worsened activity-dependent synaptic depression in rat hippocampal slices. Model: Rat slice glutamine-synthetase inhibition and evoked field-potential recordings. Limitations: The inhibitor also restricts newly synthesized glutamine; recycling is not the only possible affected source. Evidence access: Primary full text A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
Complete structured claim and evidence
Adding 500 micromolar glutamine prevented or reversed the activity-dependent loss of glutamate-mediated synaptic responses in the tested rat slices.
L-Glutamine → Rat hippocampal local glutamate supply for release source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Rat hippocampal/cortical slices with high-frequency stimulation, with or without prior enzyme inhibition.
limitations
Bath addition of glutamine is not oral L-glutamate treatment or proof of improved human cognition.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Providing a usable precursor bypassed part of the local synthesis limitation.
primary_references
A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 146–152
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hippocampal/cortical slices with high-frequency stimulation, with or without prior enzyme inhibition. · source_derived_draft · unverified_draft
## glutamate-recycling-glutamine-rescue Providing a usable precursor bypassed part of the local synthesis limitation. Adding 500 micromolar glutamine prevented or reversed the activity-dependent loss of glutamate-mediated synaptic responses in the tested rat slices. Model: Rat hippocampal/cortical slices with high-frequency stimulation, with or without prior enzyme inhibition. Limitations: Bath addition of glutamine is not oral L-glutamate treatment or proof of improved human cognition. Evidence access: Primary full text A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
Complete structured claim and evidence
At 0.2 Hz, evoked responses remained stable for 60 minutes despite prior glutamine-synthetase inhibition in the rat slice experiment.
Low-frequency stimulation in rat hippocampal slices → Rat hippocampal local glutamate supply for release source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Rat hippocampal slices; matched low-frequency recording control.
limitations
This limited period of preserved function does not make glutamine synthesis dispensable.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A stored reserve can hide a supply defect when demand is low.
primary_references
A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 154–160
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat hippocampal slices; matched low-frequency recording control. · source_derived_draft · unverified_draft
## glutamate-recycling-low-demand A stored reserve can hide a supply defect when demand is low. At 0.2 Hz, evoked responses remained stable for 60 minutes despite prior glutamine-synthetase inhibition in the rat slice experiment. Model: Rat hippocampal slices; matched low-frequency recording control. Limitations: This limited period of preserved function does not make glutamine synthesis dispensable. Evidence access: Primary full text A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24559677/ · DOI 10.1016/j.neuron.2013.12.026
Complete structured claim and evidence
The GLUD1 study identifies glutamate oxidation to 2-oxoglutarate as the enzyme reaction underlying its metabolic and regulatory investigation.
GLUD1 → 2-Oxoglutarate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Established reaction described in a primary human GLUD1 genetic/functional study.
limitations
Reaction background is distinguished from the directly measured mutant regulation; this record does not quantify tissue flux.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Removing amino nitrogen connects glutamate with the central carbon cycle.
primary_references
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 162–168
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established reaction described in a primary human GLUD1 genetic/functional study. · source_derived_draft · unverified_draft
## glutamate-gdh-oxidation Removing amino nitrogen connects glutamate with the central carbon cycle. The GLUD1 study identifies glutamate oxidation to 2-oxoglutarate as the enzyme reaction underlying its metabolic and regulatory investigation. Model: Established reaction described in a primary human GLUD1 genetic/functional study. Limitations: Reaction background is distinguished from the directly measured mutant regulation; this record does not quantify tissue flux. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
Complete structured claim and evidence
Human GLUD1 activity was inhibited by GTP; patient-derived regulatory variants showed reduced sensitivity to that inhibition.
Guanosine triphosphate → GLUD1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human lymphoblast enzyme assays from eight unrelated affected children and controls.
limitations
GTP regulation is not evidence that dietary purines or glutamate normalize the disease.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
An energy-related nucleotide restrains glutamate oxidation.
primary_references
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 170–176
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lymphoblast enzyme assays from eight unrelated affected children and controls. · source_derived_draft · unverified_draft
## glutamate-gdh-gtp-control An energy-related nucleotide restrains glutamate oxidation. Human GLUD1 activity was inhibited by GTP; patient-derived regulatory variants showed reduced sensitivity to that inhibition. Model: Human lymphoblast enzyme assays from eight unrelated affected children and controls. Limitations: GTP regulation is not evidence that dietary purines or glutamate normalize the disease. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
Complete structured claim and evidence
Expressing a patient GLUD1 mutant in COS7 cells reproduced reduced GTP inhibition observed in the patient lymphoblasts.
Human GLUD1 regulatory mutations → GLUD1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation.
limitations
Host cell species and human protein identity are distinct; no intake intervention was tested.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Changing the enzyme altered its response to a brake.
primary_references
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 178–184
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation. · source_derived_draft · unverified_draft
## glutamate-gdh-regulatory-variants Changing the enzyme altered its response to a brake. Expressing a patient GLUD1 mutant in COS7 cells reproduced reduced GTP inhibition observed in the patient lymphoblasts. Model: Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation. Limitations: Host cell species and human protein identity are distinct; no intake intervention was tested. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904
Complete structured claim and evidence
Leucine activation of lymphoblast GDH varied among twelve patients with hyperinsulinism/hyperammonemia; reduced leucine sensitivity tracked failure of leucine restriction to improve glucose in four patients.
L-Leucine → GLUD1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human patient series with enzyme allostery and dietary-response observations.
limitations
Observational genotype/phenotype evidence, not a controlled general-population dietary trial.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Another amino acid regulates how glutamate is processed, but the response varies by enzyme defect.
primary_references
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 186–192
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human patient series with enzyme allostery and dietary-response observations. · source_derived_draft · unverified_draft
## glutamate-gdh-leucine-context Another amino acid regulates how glutamate is processed, but the response varies by enzyme defect. Leucine activation of lymphoblast GDH varied among twelve patients with hyperinsulinism/hyperammonemia; reduced leucine sensitivity tracked failure of leucine restriction to improve glucose in four patients. Model: Human patient series with enzyme allostery and dietary-response observations. Limitations: Observational genotype/phenotype evidence, not a controlled general-population dietary trial. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
Complete structured claim and evidence
Hyperammonemia persisted despite protein/leucine restriction in the reported twelve-patient series.
Protein/leucine restriction in the GLUD1 patient series → Persistent hyperammonemia in human GLUD1 disease source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human rare-disease clinical series.
limitations
This does not establish treatment futility across all regimens or justify dietary advice outside the study.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Changing a regulator or diet did not correct every downstream outcome.
primary_references
Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 194–200
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human rare-disease clinical series. · source_derived_draft · unverified_draft
## glutamate-gdh-ammonia-limit Changing a regulator or diet did not correct every downstream outcome. Hyperammonemia persisted despite protein/leucine restriction in the reported twelve-patient series. Model: Human rare-disease clinical series. Limitations: This does not establish treatment futility across all regimens or justify dietary advice outside the study. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11518822/ · DOI 10.1203/00006450-200109000-00010
Complete structured claim and evidence
The primary study identifies GLS2 as a mitochondrial glutaminase hydrolyzing glutamine to glutamate.
Human glutaminase 2 / GLS2 → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human-cell GLS2/p53 study; reaction identity described alongside functional experiments.
limitations
GLS2 and the distinct GLS gene are not interchangeable.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A related amino acid is an upstream source of glutamate.
primary_references
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 202–208
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell GLS2/p53 study; reaction identity described alongside functional experiments. · source_derived_draft · unverified_draft
## glutamate-gls2-production A related amino acid is an upstream source of glutamate. The primary study identifies GLS2 as a mitochondrial glutaminase hydrolyzing glutamine to glutamate. Model: Human-cell GLS2/p53 study; reaction identity described alongside functional experiments. Limitations: GLS2 and the distinct GLS gene are not interchangeable. Evidence access: Primary abstract Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
Complete structured claim and evidence
Activating p53 increased GLS2 expression under stressed and unstressed conditions in the reported human-cell experiments.
Human tumor protein p53 / TP53 → Human glutaminase 2 / GLS2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human-cell p53 and GLS2 expression/perturbation assays.
limitations
A tumor-suppressor pathway is not evidence that glutamate supplementation prevents cancer.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Gene regulation changes the machinery that supplies glutamate.
primary_references
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 210–216
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell p53 and GLS2 expression/perturbation assays. · source_derived_draft · unverified_draft
## glutamate-p53-gls2 Gene regulation changes the machinery that supplies glutamate. Activating p53 increased GLS2 expression under stressed and unstressed conditions in the reported human-cell experiments. Model: Human-cell p53 and GLS2 expression/perturbation assays. Limitations: A tumor-suppressor pathway is not evidence that glutamate supplementation prevents cancer. Evidence access: Primary abstract Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
Complete structured claim and evidence
GLS2 manipulation linked increased glutamate and 2-oxoglutarate production with increased respiration and ATP generation in the tested human cells.
Human glutaminase 2 / GLS2 → Respiration and ATP production in human GLS2 experiments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human-cell GLS2 expression/perturbation study.
limitations
The effect depends on cell context; it is not a clinical energy claim.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
The generated carbon skeleton can support mitochondrial metabolism.
primary_references
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 218–224
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell GLS2 expression/perturbation study. · source_derived_draft · unverified_draft
## glutamate-gls2-energy The generated carbon skeleton can support mitochondrial metabolism. GLS2 manipulation linked increased glutamate and 2-oxoglutarate production with increased respiration and ATP generation in the tested human cells. Model: Human-cell GLS2 expression/perturbation study. Limitations: The effect depends on cell context; it is not a clinical energy claim. Evidence access: Primary abstract Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
Complete structured claim and evidence
Increasing GLS2 supported higher reduced-glutathione levels, lower reactive oxygen species and protection from peroxide-induced apoptosis in the reported cell experiments.
Human glutaminase 2 / GLS2 → GSH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human-cell GLS2/p53 and oxidative-stress experiments.
limitations
Cysteine, glycine and synthesis machinery remain necessary; glutamate is not established as the universal limiting substrate.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
The same supply route fed antioxidant chemistry as well as energy metabolism.
primary_references
Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 226–232
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell GLS2/p53 and oxidative-stress experiments. · source_derived_draft · unverified_draft
## glutamate-gls2-gsh The same supply route fed antioxidant chemistry as well as energy metabolism. Increasing GLS2 supported higher reduced-glutathione levels, lower reactive oxygen species and protection from peroxide-induced apoptosis in the reported cell experiments. Model: Human-cell GLS2/p53 and oxidative-stress experiments. Limitations: Cysteine, glycine and synthesis machinery remain necessary; glutamate is not established as the universal limiting substrate. Evidence access: Primary abstract Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20378837/ · DOI 10.1073/pnas.1001006107
Complete structured claim and evidence
Glycine increased opening frequency of NMDA-activated channels in cultured mouse brain neurons, with potentiation detected at 10 nM.
Glycine → Mouse NMDA-type receptors, subunits unresolved source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse cultured neurons and outside-out patch recordings.
limitations
The effect was distinct from strychnine-sensitive glycine receptors; it does not define an oral glycine or glutamate response.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
An amino acid usually associated with inhibition can assist an excitatory receptor.
primary_references
Glycine potentiates the NMDA response in cultured mouse brain neurons. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2433595/ · DOI 10.1038/325529a0
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 234–240
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cultured neurons and outside-out patch recordings. · source_derived_draft · unverified_draft
## glutamate-nmda-glycine An amino acid usually associated with inhibition can assist an excitatory receptor. Glycine increased opening frequency of NMDA-activated channels in cultured mouse brain neurons, with potentiation detected at 10 nM. Model: Mouse cultured neurons and outside-out patch recordings. Limitations: The effect was distinct from strychnine-sensitive glycine receptors; it does not define an oral glycine or glutamate response. Evidence access: Primary abstract Glycine potentiates the NMDA response in cultured mouse brain neurons. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2433595/ · DOI 10.1038/325529a0
Complete structured claim and evidence
Unedited calcium-permeable AMPA assemblies had substantially larger unitary conductances than fully edited GluR2 channels in the recombinant assays.
GluR2 Q/R-site editing state in AMPA assays → Recombinant GluR2/GluR4 AMPA receptor assay assemblies source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant GluR2/GluR4 assemblies expressed in HEK293 cells.
limitations
Receptor construct species is not resolved in the retrieved abstract; a human host cell does not establish a human receptor sequence. Dietary calcium or amino-acid effects were not tested.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
The receptor sequence changes how much current an excitatory signal produces.
primary_references
Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8987736/ · DOI 10.1523/JNEUROSCI.17-01-00058.1997
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 242–248
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant GluR2/GluR4 assemblies expressed in HEK293 cells. · source_derived_draft · unverified_draft
## glutamate-ampa-editing The receptor sequence changes how much current an excitatory signal produces. Unedited calcium-permeable AMPA assemblies had substantially larger unitary conductances than fully edited GluR2 channels in the recombinant assays. Model: Recombinant GluR2/GluR4 assemblies expressed in HEK293 cells. Limitations: Receptor construct species is not resolved in the retrieved abstract; a human host cell does not establish a human receptor sequence. Dietary calcium or amino-acid effects were not tested. Evidence access: Primary abstract Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8987736/ · DOI 10.1523/JNEUROSCI.17-01-00058.1997
Complete structured claim and evidence
The GluR4 flip variant conferred agonist-dependent conductance properties in the reported recombinant AMPA recordings.
GluR4 flip splice variant in AMPA assays → Recombinant GluR2/GluR4 AMPA receptor assay assemblies source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
HEK293 recombinant channel recordings with splice-variant comparisons.
limitations
An assay-specific receptor assembly is retained rather than assigning every AMPA receptor the same behavior.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Even closely related receptor variants can translate a signal differently.
primary_references
Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8987736/ · DOI 10.1523/JNEUROSCI.17-01-00058.1997
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 250–256
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HEK293 recombinant channel recordings with splice-variant comparisons. · source_derived_draft · unverified_draft
## glutamate-ampa-splice Even closely related receptor variants can translate a signal differently. The GluR4 flip variant conferred agonist-dependent conductance properties in the reported recombinant AMPA recordings. Model: HEK293 recombinant channel recordings with splice-variant comparisons. Limitations: An assay-specific receptor assembly is retained rather than assigning every AMPA receptor the same behavior. Evidence access: Primary abstract Single-channel properties of recombinant AMPA receptors depend on RNA editing, splice variation, and subunit composition. · 1997 · https://pubmed.ncbi.nlm.nih.gov/8987736/ · DOI 10.1523/JNEUROSCI.17-01-00058.1997
Complete structured claim and evidence
The cloned rat metabotropic glutamate receptor coupled receptor activation to inositol-phosphate/calcium signaling.
Rat metabotropic glutamate receptor 1 / Grm1 → Rat mGluR1 inositol-phosphate/calcium signaling source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat receptor cloning and functional expression study.
limitations
This does not demonstrate that oral inositol or calcium increases the response.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A glutamate receptor can trigger an internal signaling cascade instead of forming the ion pore itself.
primary_references
Sequence and expression of a metabotropic glutamate receptor. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1847995/ · DOI 10.1038/349760a0
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 258–264
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat receptor cloning and functional expression study. · source_derived_draft · unverified_draft
## glutamate-mgr1-ip-calcium A glutamate receptor can trigger an internal signaling cascade instead of forming the ion pore itself. The cloned rat metabotropic glutamate receptor coupled receptor activation to inositol-phosphate/calcium signaling. Model: Rat receptor cloning and functional expression study. Limitations: This does not demonstrate that oral inositol or calcium increases the response. Evidence access: Primary abstract Sequence and expression of a metabotropic glutamate receptor. · 1991 · https://pubmed.ncbi.nlm.nih.gov/1847995/ · DOI 10.1038/349760a0
Complete structured claim and evidence
Rat mGluR2 expressed in transfected cells inhibited forskolin-stimulated cAMP formation.
Rat metabotropic glutamate receptor 2 / Grm2 → Forskolin-stimulated cAMP in rat mGluR2 expression assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat receptor cDNA expressed in heterologous cells.
limitations
Do not assign the mGluR1 calcium route to every metabotropic glutamate receptor.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A different glutamate receptor couples to a different second-messenger response.
primary_references
A family of metabotropic glutamate receptors. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1309649/ · DOI 10.1016/0896-6273(92)90118-w
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 266–272
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat receptor cDNA expressed in heterologous cells. · source_derived_draft · unverified_draft
## glutamate-mgr2-camp A different glutamate receptor couples to a different second-messenger response. Rat mGluR2 expressed in transfected cells inhibited forskolin-stimulated cAMP formation. Model: Rat receptor cDNA expressed in heterologous cells. Limitations: Do not assign the mGluR1 calcium route to every metabotropic glutamate receptor. Evidence access: Primary abstract A family of metabotropic glutamate receptors. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1309649/ · DOI 10.1016/0896-6273(92)90118-w
Complete structured claim and evidence
Chloride activated glutamate uptake by purified rat VGLUT2 in reconstituted proteoliposomes.
Chloride ion → Rat vesicular glutamate transporter 2 / Slc17a6 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat VGLUT2 expressed in insect cells, purified and reconstituted; membrane-potential-driven uptake.
limitations
Chloride regulation in vesicles is not equivalent to an effect of dietary salt.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
An ion regulates whether the vesicle-loading transporter works.
primary_references
Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 274–280
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat VGLUT2 expressed in insect cells, purified and reconstituted; membrane-potential-driven uptake. · source_derived_draft · unverified_draft
## glutamate-vglut2-chloride An ion regulates whether the vesicle-loading transporter works. Chloride activated glutamate uptake by purified rat VGLUT2 in reconstituted proteoliposomes. Model: Rat VGLUT2 expressed in insect cells, purified and reconstituted; membrane-potential-driven uptake. Limitations: Chloride regulation in vesicles is not equivalent to an effect of dietary salt. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
Complete structured claim and evidence
Acetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation.
Acetoacetate → Rat vesicular glutamate transporter 2 / Slc17a6 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified rat transporter; controlled chloride/acetoacetate concentrations and washout.
limitations
This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A metabolic fuel-related molecule altered transmitter packaging in a biochemical system.
primary_references
Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 282–288
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified rat transporter; controlled chloride/acetoacetate concentrations and washout. · source_derived_draft · unverified_draft
## glutamate-vglut2-acetoacetate A metabolic fuel-related molecule altered transmitter packaging in a biochemical system. Acetoacetate reversibly inhibited reconstituted rat VGLUT2 uptake with a chloride-dependent shift consistent with competition at allosteric regulation. Model: Purified rat transporter; controlled chloride/acetoacetate concentrations and washout. Limitations: This mechanism alone does not establish the effects of fasting or a ketogenic diet in humans. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
Complete structured claim and evidence
Purified human VGLUT3 also showed chloride-dependent glutamate transport in reconstituted vesicles.
Chloride ion → Human vesicular glutamate transporter 3 / SLC17A8 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human VGLUT3 expressed in insect cells and reconstituted separately from rat VGLUT2.
limitations
Isoforms and species are kept distinct; no nutritional chloride threshold was tested.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A human transporter isoform shares a tested regulatory input.
primary_references
Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 290–296
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human VGLUT3 expressed in insect cells and reconstituted separately from rat VGLUT2. · source_derived_draft · unverified_draft
## glutamate-vglut3-chloride A human transporter isoform shares a tested regulatory input. Purified human VGLUT3 also showed chloride-dependent glutamate transport in reconstituted vesicles. Model: Human VGLUT3 expressed in insect cells and reconstituted separately from rat VGLUT2. Limitations: Isoforms and species are kept distinct; no nutritional chloride threshold was tested. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
Complete structured claim and evidence
Mouse hippocampal slices exposed to 10 mM lithium acetoacetate had lower miniature excitatory-current amplitude and frequency than lithium-chloride controls.
Acetoacetate → Mouse hippocampal miniature excitatory postsynaptic currents source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse acute slices incubated for more than two hours; lithium matched between groups.
limitations
High bath exposure and slice conditions are explicit; do not substitute an oral ketone dose or attribute the difference to unmatched lithium.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A controlled slice experiment connected the transport finding with synaptic output.
primary_references
Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 298–304
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse acute slices incubated for more than two hours; lithium matched between groups. · source_derived_draft · unverified_draft
## glutamate-ketone-synaptic-response A controlled slice experiment connected the transport finding with synaptic output. Mouse hippocampal slices exposed to 10 mM lithium acetoacetate had lower miniature excitatory-current amplitude and frequency than lithium-chloride controls. Model: Mouse acute slices incubated for more than two hours; lithium matched between groups. Limitations: High bath exposure and slice conditions are explicit; do not substitute an oral ketone dose or attribute the difference to unmatched lithium. Evidence access: Primary full text Metabolic control of vesicular glutamate transport and release. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20920794/ · DOI 10.1016/j.neuron.2010.09.002
Complete structured claim and evidence
Deleting Slc17a6 selectively in mouse dopamine neurons abolished their cultured glutamate release and greatly reduced excitatory output in mesoaccumbens slices.
Mouse vesicular glutamate transporter 2 / Slc17a6 → Glutamate release from mouse dopamine neurons source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse dopamine-neuron conditional knockout, culture and brain slices.
limitations
Cell-specific deletion is not global glutamate deficiency.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A dopamine neuron can require separate machinery to release glutamate too.
primary_references
Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 306–312
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse dopamine-neuron conditional knockout, culture and brain slices. · source_derived_draft · unverified_draft
## glutamate-vglut2-dopamine-neuron-release A dopamine neuron can require separate machinery to release glutamate too. Deleting Slc17a6 selectively in mouse dopamine neurons abolished their cultured glutamate release and greatly reduced excitatory output in mesoaccumbens slices. Model: Mouse dopamine-neuron conditional knockout, culture and brain slices. Limitations: Cell-specific deletion is not global glutamate deficiency. Evidence access: Primary full text Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012
Complete structured claim and evidence
Glutamate co-entry increased vesicular acidification in the study, supporting the pH gradient used for monoamine storage.
L-Glutamate → Vesicular pH gradient in rodent monoamine-storage experiments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rodent synaptic-vesicle acidification assays; glutamate compared with chloride.
limitations
The preparation does not show that glutamate supplements increase human dopamine.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
One transmitter can influence storage of another through shared vesicle chemistry.
primary_references
Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 314–320
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rodent synaptic-vesicle acidification assays; glutamate compared with chloride. · source_derived_draft · unverified_draft
## glutamate-glutamate-vesicle-acidification One transmitter can influence storage of another through shared vesicle chemistry. Glutamate co-entry increased vesicular acidification in the study, supporting the pH gradient used for monoamine storage. Model: Rodent synaptic-vesicle acidification assays; glutamate compared with chloride. Limitations: The preparation does not show that glutamate supplements increase human dopamine. Evidence access: Primary full text Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012
Complete structured claim and evidence
Dopamine-neuron Slc17a6 deletion reduced dopamine stores in ventral-striatal projections and reduced cocaine-stimulated locomotor responses while sparing baseline motor behavior.
Mouse vesicular glutamate transporter 2 / Slc17a6 → Mouse ventral-striatal dopamine stores source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse conditional knockout with tissue dopamine and behavioral measurements.
limitations
Multiple downstream effects coexist; this does not prove every dopamine neuron or behavior depends equally on VGLUT2.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Removing the glutamate-loading route changed another transmitter system in a specific circuit.
primary_references
Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 322–328
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse conditional knockout with tissue dopamine and behavioral measurements. · source_derived_draft · unverified_draft
## glutamate-vglut2-dopamine-stores Removing the glutamate-loading route changed another transmitter system in a specific circuit. Dopamine-neuron Slc17a6 deletion reduced dopamine stores in ventral-striatal projections and reduced cocaine-stimulated locomotor responses while sparing baseline motor behavior. Model: Mouse conditional knockout with tissue dopamine and behavioral measurements. Limitations: Multiple downstream effects coexist; this does not prove every dopamine neuron or behavior depends equally on VGLUT2. Evidence access: Primary full text Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20223200/ · DOI 10.1016/j.neuron.2010.02.012
Complete structured claim and evidence
Added extracellular glutamate inhibited cystine uptake in N18-RE-105 neuronal hybrid cells, and toxicity tracked that inhibition.
L-Glutamate → Cystine uptake in N18-RE-105 neuronal hybrid cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Neuroblastoma/primary-retina hybrid-cell culture; transport and toxicity assays.
limitations
The early paper does not genetically resolve SLC7A11; it is not an oral glutamate exposure study.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
The same molecule used to build an antioxidant can obstruct another required ingredient when outside these cells.
primary_references
Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 330–336
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neuroblastoma/primary-retina hybrid-cell culture; transport and toxicity assays. · source_derived_draft · unverified_draft
## glutamate-extracellular-cystine-block The same molecule used to build an antioxidant can obstruct another required ingredient when outside these cells. Added extracellular glutamate inhibited cystine uptake in N18-RE-105 neuronal hybrid cells, and toxicity tracked that inhibition. Model: Neuroblastoma/primary-retina hybrid-cell culture; transport and toxicity assays. Limitations: The early paper does not genetically resolve SLC7A11; it is not an oral glutamate exposure study. Evidence access: Primary abstract Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3
Complete structured claim and evidence
Extracellular glutamate exposure lowered glutathione and increased intracellular peroxides in N18-RE-105 cells alongside inhibited cystine uptake.
Extracellular glutamate challenge in N18-RE-105 cells → Oxidative injury in N18-RE-105 neuronal hybrid cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Neuronal hybrid-cell transport, glutathione and peroxide assays.
limitations
A specific experimental toxicity mechanism is retained without inferring normal food-related brain injury.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Oxidative injury arose through precursor supply, a different route from opening an excitatory receptor.
primary_references
Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 338–344
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neuronal hybrid-cell transport, glutathione and peroxide assays. · source_derived_draft · unverified_draft
## glutamate-extracellular-gsh-loss Oxidative injury arose through precursor supply, a different route from opening an excitatory receptor. Extracellular glutamate exposure lowered glutathione and increased intracellular peroxides in N18-RE-105 cells alongside inhibited cystine uptake. Model: Neuronal hybrid-cell transport, glutathione and peroxide assays. Limitations: A specific experimental toxicity mechanism is retained without inferring normal food-related brain injury. Evidence access: Primary abstract Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3
Complete structured claim and evidence
Lowering culture-medium cystine mimicked glutamate-associated glutathione loss and oxidative cytotoxicity in N18-RE-105 cells.
Low-cystine medium in N18-RE-105 cultures → Oxidative injury in N18-RE-105 neuronal hybrid cells source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Neuronal hybrid-cell nutrient-withdrawal experiment.
limitations
The deficient precursor is cystine/cysteine supply, not glutamate; no human dietary threshold is established.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Removing the missing precursor reproduced the supply failure.
primary_references
Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 346–352
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Neuronal hybrid-cell nutrient-withdrawal experiment. · source_derived_draft · unverified_draft
## glutamate-cystine-shortage Removing the missing precursor reproduced the supply failure. Lowering culture-medium cystine mimicked glutamate-associated glutathione loss and oxidative cytotoxicity in N18-RE-105 cells. Model: Neuronal hybrid-cell nutrient-withdrawal experiment. Limitations: The deficient precursor is cystine/cysteine supply, not glutamate; no human dietary threshold is established. Evidence access: Primary abstract Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. · 1989 · https://pubmed.ncbi.nlm.nih.gov/2576375/ · DOI 10.1016/0896-6273(89)90043-3
Complete structured claim and evidence
Glutamate at 10 nM promoted integrin-mediated adhesion of tested human T cells to laminin and fibronectin; AMPA antagonists and relevant anti-integrin antibodies blocked the response.
L-Glutamate → Glutamate-evoked human T-cell adhesion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human T-cell receptor expression and adhesion assays.
limitations
Antagonist support does not uniquely prove GluA3 is the sole functional subunit; no dietary immune benefit is established.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
An extracellular amino acid changed immune-cell behavior in an assay.
primary_references
Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12682273/ · DOI 10.4049/jimmunol.170.8.4362
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 354–360
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human T-cell receptor expression and adhesion assays. · source_derived_draft · unverified_draft
## glutamate-immune-adhesion An extracellular amino acid changed immune-cell behavior in an assay. Glutamate at 10 nM promoted integrin-mediated adhesion of tested human T cells to laminin and fibronectin; AMPA antagonists and relevant anti-integrin antibodies blocked the response. Model: Human T-cell receptor expression and adhesion assays. Limitations: Antagonist support does not uniquely prove GluA3 is the sole functional subunit; no dietary immune benefit is established. Evidence access: Primary abstract Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12682273/ · DOI 10.4049/jimmunol.170.8.4362
Complete structured claim and evidence
Glutamate increased CXCR4-mediated T-cell chemotactic migration toward CXCL12 in the reported experiments.
L-Glutamate → Human T-cell migration toward CXCL12 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human T-cell chemotaxis experiments in the receptor study.
limitations
This does not establish disease causation or the direction of a clinical immune effect.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A metabolic signal interacted with a chemokine-guided movement system.
primary_references
Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12682273/ · DOI 10.4049/jimmunol.170.8.4362
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 362–368
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human T-cell chemotaxis experiments in the receptor study. · source_derived_draft · unverified_draft
## glutamate-immune-migration A metabolic signal interacted with a chemokine-guided movement system. Glutamate increased CXCR4-mediated T-cell chemotactic migration toward CXCL12 in the reported experiments. Model: Human T-cell chemotaxis experiments in the receptor study. Limitations: This does not establish disease causation or the direction of a clinical immune effect. Evidence access: Primary abstract Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12682273/ · DOI 10.4049/jimmunol.170.8.4362
Complete structured claim and evidence
Human mitochondrial glutamyl-tRNA synthetase attached glutamate to mitochondrial tRNA(Gln), generating the intermediate Glu-tRNA(Gln).
Human mitochondrial glutamyl-tRNA synthetase / EARS2 → Human mitochondrial glutamyl-tRNA(Gln) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human enzyme and mitochondrial tRNA biochemistry.
limitations
This intermediate is not glutamate being correctly incorporated at glutamine codons.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A deliberately intermediate amino-acid attachment must be processed before translation.
primary_references
Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 370–376
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme and mitochondrial tRNA biochemistry. · source_derived_draft · unverified_draft
## glutamate-ears2-intermediate A deliberately intermediate amino-acid attachment must be processed before translation. Human mitochondrial glutamyl-tRNA synthetase attached glutamate to mitochondrial tRNA(Gln), generating the intermediate Glu-tRNA(Gln). Model: Recombinant human enzyme and mitochondrial tRNA biochemistry. Limitations: This intermediate is not glutamate being correctly incorporated at glutamine codons. Evidence access: Primary abstract Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
Complete structured claim and evidence
Recombinant human mtGluRS and GatCAB reconstituted formation of glutaminyl-tRNA(Gln) through the glutamylated intermediate in vitro.
Human mitochondrial GatCAB amidotransferase → Human mitochondrial glutaminyl-tRNA(Gln) source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human recombinant mitochondrial tRNA pathway reconstitution.
limitations
Each complex subunit is separately modeled; an amino acid supplement was not the tested intervention.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A second enzyme complex converts the attached amino acid to the required one.
primary_references
Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 378–384
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant mitochondrial tRNA pathway reconstitution. · source_derived_draft · unverified_draft
## glutamate-gatcab-conversion A second enzyme complex converts the attached amino acid to the required one. Recombinant human mtGluRS and GatCAB reconstituted formation of glutaminyl-tRNA(Gln) through the glutamylated intermediate in vitro. Model: Human recombinant mitochondrial tRNA pathway reconstitution. Limitations: Each complex subunit is separately modeled; an amino acid supplement was not the tested intervention. Evidence access: Primary abstract Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
Complete structured claim and evidence
Knocking down any human GatCAB subunit caused accumulation of glutamate-charged tRNA(Gln) and impaired respiration.
Human mitochondrial GatCAB amidotransferase → Respiration in human GatCAB knockdown cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human-cell siRNA against GatCAB subunits.
limitations
Knockdown establishes a machinery dependency, not dietary glutamate or glutamine deficiency.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Available amino acid cannot replace the missing processing step.
primary_references
Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 386–392
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell siRNA against GatCAB subunits. · source_derived_draft · unverified_draft
## glutamate-gatcab-loss Available amino acid cannot replace the missing processing step. Knocking down any human GatCAB subunit caused accumulation of glutamate-charged tRNA(Gln) and impaired respiration. Model: Human-cell siRNA against GatCAB subunits. Limitations: Knockdown establishes a machinery dependency, not dietary glutamate or glutamine deficiency. Evidence access: Primary abstract Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
Complete structured claim and evidence
The glutamate-mischarged tRNA(Gln) intermediate bound mitochondrial EF-Tu weakly, supporting exclusion from translation before correction.
Human mitochondrial glutamyl-tRNA(Gln) → Human mitochondrial elongation factor Tu / TUFM source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human mitochondrial tRNA binding assays.
limitations
Weak affinity supports the proposed quality-control mechanism; it does not prove absolute exclusion under every condition.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Quality control reduces entry of the unfinished intermediate into protein synthesis.
primary_references
Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 394–400
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human mitochondrial tRNA binding assays. · source_derived_draft · unverified_draft
## glutamate-elongation-quality-control Quality control reduces entry of the unfinished intermediate into protein synthesis. The glutamate-mischarged tRNA(Gln) intermediate bound mitochondrial EF-Tu weakly, supporting exclusion from translation before correction. Model: Human mitochondrial tRNA binding assays. Limitations: Weak affinity supports the proposed quality-control mechanism; it does not prove absolute exclusion under every condition. Evidence access: Primary abstract Biogenesis of glutaminyl-mt tRNAGln in human mitochondria. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19805282/ · DOI 10.1073/pnas.0907602106
Complete structured claim and evidence
Patient fibroblasts with EARS2 p.G317C had broad metabolic abnormalities; reconstitution with wild-type versus disease variants distinguished severity-related TCA and amino-acid signatures.
Human pathogenic EARS2 variants → Metabolism in human EARS2-deficient fibroblasts source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human neonatal case, primary fibroblasts and variant reconstitution/metabolomics.
limitations
Patient-derived cells and rescue constructs are not dietary supplementation experiments.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A glutamate-handling translation enzyme can affect many downstream metabolic pools.
primary_references
Metabolic impact of pathogenic variants in the mitochondrial glutamyl-tRNA synthetase EARS2. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33855712/ · DOI 10.1002/jimd.12387
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 402–408
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human neonatal case, primary fibroblasts and variant reconstitution/metabolomics. · source_derived_draft · unverified_draft
## glutamate-ears2-disease-metabolism A glutamate-handling translation enzyme can affect many downstream metabolic pools. Patient fibroblasts with EARS2 p.G317C had broad metabolic abnormalities; reconstitution with wild-type versus disease variants distinguished severity-related TCA and amino-acid signatures. Model: Human neonatal case, primary fibroblasts and variant reconstitution/metabolomics. Limitations: Patient-derived cells and rescue constructs are not dietary supplementation experiments. Evidence access: Primary full text Metabolic impact of pathogenic variants in the mitochondrial glutamyl-tRNA synthetase EARS2. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33855712/ · DOI 10.1002/jimd.12387
Complete structured claim and evidence
Recombinant mouse TTLL7 favored beta-tubulin polyglutamylation in vitro and when expressed in HEK293T cells.
Mouse tubulin polyglutamylase / Ttll7 → Beta-tubulin polyglutamylation in mouse TTLL7 assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and full-text construct methods
experimental_model
Mouse cDNA constructs, recombinant biochemistry and human host-cell expression.
limitations
This protein modification differs from a free-glutamate receptor signal; the beta-tubulin isoform is not assigned beyond the study.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
Glutamate can be added in side chains that modify a structural protein.
primary_references
TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16901895/ · DOI 10.1074/jbc.M603984200
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 410–416
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cDNA constructs, recombinant biochemistry and human host-cell expression. · source_derived_draft · unverified_draft
## glutamate-tubulin-glutamylation Glutamate can be added in side chains that modify a structural protein. Recombinant mouse TTLL7 favored beta-tubulin polyglutamylation in vitro and when expressed in HEK293T cells. Model: Mouse cDNA constructs, recombinant biochemistry and human host-cell expression. Limitations: This protein modification differs from a free-glutamate receptor signal; the beta-tubulin isoform is not assigned beyond the study. Evidence access: Primary abstract and full-text construct methods TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16901895/ · DOI 10.1074/jbc.M603984200
Complete structured claim and evidence
Ttll7 siRNA in rat PC12 cells reduced nerve-growth-factor-stimulated MAP2-positive neurite growth.
Rat tubulin polyglutamylase / Ttll7 → MAP2-positive neurite growth in rat PC12 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract and primary full text
experimental_model
Rat PC12 cell knockdown and nerve-growth-factor differentiation.
limitations
Loss of enzyme function does not establish a free-glutamate dietary shortage or brain-regeneration treatment.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
A glutamate-chain-adding enzyme contributed to cell shape in a differentiation model.
primary_references
TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16901895/ · DOI 10.1074/jbc.M603984200
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 418–424
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat PC12 cell knockdown and nerve-growth-factor differentiation. · source_derived_draft · unverified_draft
## glutamate-ttll7-neurite-loss A glutamate-chain-adding enzyme contributed to cell shape in a differentiation model. Ttll7 siRNA in rat PC12 cells reduced nerve-growth-factor-stimulated MAP2-positive neurite growth. Model: Rat PC12 cell knockdown and nerve-growth-factor differentiation. Limitations: Loss of enzyme function does not establish a free-glutamate dietary shortage or brain-regeneration treatment. Evidence access: Primary abstract and primary full text TTLL7 is a mammalian beta-tubulin polyglutamylase required for growth of MAP2-positive neurites. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16901895/ · DOI 10.1074/jbc.M603984200
Complete structured claim and evidence
Current reversal measurements supported uptake of one glutamate anion with three sodium ions and one proton, coupled to outward movement of one potassium ion.
Mammalian glial glutamate transporter GLT-1 in the CHO assay → L-Glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"}
experimental_model
Whole-cell current reversal measurements
exposure
Ion substitution, intracellular sodium/glutamate and extracellular potassium
limitations
Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Mammalian GLT-1 expressed in Chinese hamster ovary cells
plain_language
Glutamate clearance uses sodium, potassium and proton gradients together.
primary_references
[sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998
tissue_or_cell_type
Plasma membrane
transport_effect
raises Uptake of one glutamate anion with three sodium ions and one proton.
transport_pool
the expressing cell Uptake of one glutamate anion with three sodium ions and one proton.
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 369–380
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell current reversal measurements · source_derived_draft · unverified_draft
### sodium-glt1-stoichiometry Current reversal measurements supported uptake of one glutamate anion with three sodium ions and one proton, coupled to outward movement of one potassium ion. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutamate clearance uses sodium, potassium and proton gradients together. organism: Mammalian GLT-1 expressed in Chinese hamster ovary cells tissue_or_cell_type: Plasma membrane experimental_model: Whole-cell current reversal measurements limitations: Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result. exposure: Ion substitution, intracellular sodium/glutamate and extracellular potassium evidence_span: {"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"} [sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998
Complete structured claim and evidence
Increasing extracellular potassium around cells loaded with sodium and glutamate evoked an outward, blocker-sensitive reversed transport current.
Potassium ion → GLT-1-mediated reversed glutamate transport source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"}
experimental_model
Whole-cell current reversal measurements
exposure
Ion substitution, intracellular sodium/glutamate and extracellular potassium
limitations
Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Mammalian GLT-1 expressed in Chinese hamster ovary cells
plain_language
Changing the ion gradients can reverse a transporter that normally clears glutamate.
primary_references
[sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998
tissue_or_cell_type
Plasma membrane
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 382–393
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Whole-cell current reversal measurements · source_derived_draft · unverified_draft
### sodium-glt1-reversal Increasing extracellular potassium around cells loaded with sodium and glutamate evoked an outward, blocker-sensitive reversed transport current. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the ion gradients can reverse a transporter that normally clears glutamate. organism: Mammalian GLT-1 expressed in Chinese hamster ovary cells tissue_or_cell_type: Plasma membrane experimental_model: Whole-cell current reversal measurements limitations: Stoichiometry inferred from reversal potentials; the predicted ischemic extracellular glutamate concentration is not an in-vivo result. exposure: Ion substitution, intracellular sodium/glutamate and extracellular potassium evidence_span: {"source_cache": "artifacts/sodium-research/9822723.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064", "start_char": 0, "end_char": 1740, "text_sha256": "7612750fb1528dcd6212222b248bc74a2ec7a3813f50cbe5cf8ccdadbe448064"} [sodium-p9822723] Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake. (1998). https://pubmed.ncbi.nlm.nih.gov/9822723/ DOI: 10.1523/jneurosci.18-23-09620.1998
Complete structured claim and evidence
Human recessive SLC1A1 R445W and I395del variants were identified in dicarboxylic aminoaciduria with urinary glutamate and aspartate loss.
Human SLC1A1 R445W and I395del variants → Renal conservation of glutamate and aspartate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human families and functional characterization of disease-associated human transporter variants.
limitations
Gene-related renal handling is not evidence of an ordinary dietary deficiency; neurological associations do not establish one mechanism.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A transporter defect can cause nutrient loss even when intake is adequate.
primary_references
Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 34–40
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human families and functional characterization of disease-associated human transporter variants. · source_derived_draft · unverified_draft
## l-aspartate-renal-gene-loss A transporter defect can cause nutrient loss even when intake is adequate. Human recessive SLC1A1 R445W and I395del variants were identified in dicarboxylic aminoaciduria with urinary glutamate and aspartate loss. Model: Human families and functional characterization of disease-associated human transporter variants. Limitations: Gene-related renal handling is not evidence of an ordinary dietary deficiency; neurological associations do not establish one mechanism. Evidence access: Primary abstract Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
Complete structured claim and evidence
The disease-associated human SLC1A1 variants showed near-absent cell-surface expression in a canine kidney cell model, with impaired glutamate and cysteine transport in functional assays.
Human SLC1A1 R445W and I395del variants → Human excitatory amino acid transporter 3 / SLC1A1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human constructs in heterologous functional assays and canine MDCK cells.
limitations
The accessed abstract reports glutamate/cysteine assays; do not mislabel them as direct aspartate uptake measurements.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Having a transporter gene is insufficient if the protein fails to reach the membrane.
primary_references
Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 42–48
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human constructs in heterologous functional assays and canine MDCK cells. · source_derived_draft · unverified_draft
## l-aspartate-renal-trafficking Having a transporter gene is insufficient if the protein fails to reach the membrane. The disease-associated human SLC1A1 variants showed near-absent cell-surface expression in a canine kidney cell model, with impaired glutamate and cysteine transport in functional assays. Model: Human constructs in heterologous functional assays and canine MDCK cells. Limitations: The accessed abstract reports glutamate/cysteine assays; do not mislabel them as direct aspartate uptake measurements. Evidence access: Primary abstract Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
Complete structured claim and evidence
Human hxCTb required 4F2hc for sodium-independent cystine/glutamate transport in oocytes.
SLC7A11 → Cystine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/11406111.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc", "start_char": 0, "end_char": 1364, "text_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc"}
experimental_model
Human xCT expression and oxidative-stress response
exposure
hxCTb with 4F2hc; diethyl maleate challenge
limitations
Sodium independence belongs to this transporter; other cysteine-entry routes differ.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human transporter; Xenopus expression host
plain_language
The precursor-entry route depends on two transporter subunits.
primary_references
[glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8
tissue_or_cell_type
Oocyte membranes and human U87 glioma cells
transport_effect
depends The record names the cystine/glutamate exchange pair and the 4F2hc requirement, not which way cystine crossed.
transport_pool
the cytosol across the plasma membrane The record names the cystine/glutamate exchange pair and the 4F2hc requirement, not which way cystine crossed.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 736–747
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human xCT expression and oxidative-stress response · source_derived_draft · unverified_draft
### glutathione-xct-cystine Human hxCTb required 4F2hc for sodium-independent cystine/glutamate transport in oocytes. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor-entry route depends on two transporter subunits. organism: Human transporter; Xenopus expression host tissue_or_cell_type: Oocyte membranes and human U87 glioma cells experimental_model: Human xCT expression and oxidative-stress response limitations: Sodium independence belongs to this transporter; other cysteine-entry routes differ. exposure: hxCTb with 4F2hc; diethyl maleate challenge evidence_span: {"source_cache": "artifacts/glutathione-research/11406111.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc", "start_char": 0, "end_char": 1364, "text_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc"} [glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8
Complete structured claim and evidence
Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step.
Human glutamate-cysteine ligase catalytic subunit / GCLC → Gamma-glutamylcysteine source_derived_draftungraded
Experimental context and source evidence
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": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"}
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 machinery still needs its amino-acid building blocks.
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 840–851
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-gcl-first-step Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced machinery still needs its amino-acid building blocks. 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": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"} [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
Complete structured claim and evidence
The human GCL holoenzyme was more active and less sensitive to glutathione inhibition than its catalytic subunit alone.
Human glutamate-cysteine ligase modifier subunit / GCLM → Human glutamate-cysteine ligase catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"}
experimental_model
Purified recombinant subunit/holoenzyme kinetics
exposure
Substrate comparisons and glutathione inhibition
limitations
Baseline enzymology, not a sulforaphane or nutrient-repletion trial.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GCLC and GCLM expressed in insect cells
plain_language
The modifier subunit changes how the glutathione-building enzyme works.
primary_references
[sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
tissue_or_cell_type
Glutathione synthesis first-step enzyme
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 814–825
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant subunit/holoenzyme kinetics · source_derived_draft · unverified_draft
### sulforaphane-gclm-activity The human GCL holoenzyme was more active and less sensitive to glutathione inhibition than its catalytic subunit alone. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The modifier subunit changes how the glutathione-building enzyme works. organism: Human GCLC and GCLM expressed in insect cells tissue_or_cell_type: Glutathione synthesis first-step enzyme experimental_model: Purified recombinant subunit/holoenzyme kinetics limitations: Baseline enzymology, not a sulforaphane or nutrient-repletion trial. exposure: Substrate comparisons and glutathione inhibition evidence_span: {"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"} [sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
Complete structured claim and evidence
Glutathione inhibited both human GCLC and GCL holoenzyme, with greater sensitivity of GCLC alone.
GSH → Human glutamate-cysteine ligase catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"}
experimental_model
Purified recombinant subunit/holoenzyme kinetics
exposure
Substrate comparisons and glutathione inhibition
limitations
Baseline enzymology, not a sulforaphane or nutrient-repletion trial.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GCLC and GCLM expressed in insect cells
plain_language
The product feeds back on the machinery that makes more of it.
primary_references
[sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
tissue_or_cell_type
Glutathione synthesis first-step enzyme
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 827–838
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant subunit/holoenzyme kinetics · source_derived_draft · unverified_draft
### sulforaphane-gsh-feedback Glutathione inhibited both human GCLC and GCL holoenzyme, with greater sensitivity of GCLC alone. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The product feeds back on the machinery that makes more of it. organism: Human GCLC and GCLM expressed in insect cells tissue_or_cell_type: Glutathione synthesis first-step enzyme experimental_model: Purified recombinant subunit/holoenzyme kinetics limitations: Baseline enzymology, not a sulforaphane or nutrient-repletion trial. exposure: Substrate comparisons and glutathione inhibition evidence_span: {"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"} [sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
Complete structured claim and evidence
Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine.
Glutamine synthetase / GLUL → L-Glutamine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human GLUL ligand-complex crystal structures; canine apoenzyme comparison
exposure
ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes
limitations
Reaction identity does not determine the predominant metal in living human brain.
nutrient_topic
Manganese research collection; topical membership is not evidence of a direct dietary effect. · Manganese
organism
Homo sapiens protein
plain_language
GLUL combines glutamate and ammonia using ATP.
primary_references
[mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
tissue_or_cell_type
Purified GLUL
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 596–606
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLUL ligand-complex crystal structures; canine apoenzyme comparison · source_derived_draft · unverified_draft
### mn-enz-glul-reaction Human glutamine synthetase catalyzes ATP-coupled ligation of glutamate and ammonia to make glutamine. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: GLUL combines glutamate and ammonia using ATP. organism: Homo sapiens protein tissue_or_cell_type: Purified GLUL experimental_model: Human GLUL ligand-complex crystal structures; canine apoenzyme comparison limitations: Reaction identity does not determine the predominant metal in living human brain. exposure: ADP/phosphate/Mn and ADP/phosphorylated-inhibitor/Mn complexes [mn-enz-18005987] Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design. (2008). https://pubmed.ncbi.nlm.nih.gov/18005987/ DOI: 10.1016/j.jmb.2007.10.029
Complete structured claim and evidence
Human GOT1 catalyzes reversible amino transfer between aspartate and 2-oxoglutarate, producing oxaloacetate and glutamate.
Human cytosolic aspartate aminotransferase / GOT1 → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human cytosolic GOT1 and GPT; coupled kinetic assays
exposure
Kinetic assays at pH 7.4 and 37 C
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This B6-dependent enzyme links amino-acid and carbon metabolism.
primary_references
[b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 741–751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human cytosolic GOT1 and GPT; coupled kinetic assays · source_derived_draft · unverified_draft
### b6-met-got1-reaction Human GOT1 catalyzes reversible amino transfer between aspartate and 2-oxoglutarate, producing oxaloacetate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent enzyme links amino-acid and carbon metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human cytosolic GOT1 and GPT; coupled kinetic assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. exposure: Kinetic assays at pH 7.4 and 37 C [b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
Complete structured claim and evidence
Human GPT catalyzes reversible amino transfer between alanine and 2-oxoglutarate, producing pyruvate and glutamate.
Human cytosolic alanine aminotransferase / GPT → L-Alanine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human cytosolic GOT1 and GPT; coupled kinetic assays
exposure
Kinetic assays at pH 7.4 and 37 C
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6-dependent alanine transamination links nitrogen transfer to pyruvate metabolism.
primary_references
[b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 753–763
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human cytosolic GOT1 and GPT; coupled kinetic assays · source_derived_draft · unverified_draft
### b6-met-gpt-reaction Human GPT catalyzes reversible amino transfer between alanine and 2-oxoglutarate, producing pyruvate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent alanine transamination links nitrogen transfer to pyruvate metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human cytosolic GOT1 and GPT; coupled kinetic assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. exposure: Kinetic assays at pH 7.4 and 37 C [b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
Complete structured claim and evidence
Human BCAT1 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.
Human cytosolic branched-chain aminotransferase / BCAT1 → L-Leucine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions.
experimental_model
Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate.
primary_references
[b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–727
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures · source_derived_draft · unverified_draft
### b6-met-bcat1-leucine Human BCAT1 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions. [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
Complete structured claim and evidence
Human BCAT2 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.
Human mitochondrial branched-chain aminotransferase / BCAT2 → L-Leucine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions.
experimental_model
Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate.
primary_references
[b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 729–739
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures · source_derived_draft · unverified_draft
### b6-met-bcat2-leucine Human BCAT2 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions. [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
Complete structured claim and evidence
PLP-bound human GAD67 catalyzes glutamate decarboxylation to GABA.
Human glutamate decarboxylase 67 / GAD1 → Gamma-aminobutyric acid source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human GAD isoforms; crystallography and enzyme kinetics
exposure
Glutamate turnover in recombinant enzyme assays.
limitations
Recombinant chemistry does not establish a human supplementation response.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Activated B6 helps this enzyme make GABA.
primary_references
[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 949–959
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GAD isoforms; crystallography and enzyme kinetics · source_derived_draft · unverified_draft
### b6-neuro-gad1-gaba PLP-bound human GAD67 catalyzes glutamate decarboxylation to GABA. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated B6 helps this enzyme make GABA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics limitations: Recombinant chemistry does not establish a human supplementation response. exposure: Glutamate turnover in recombinant enzyme assays. [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
Complete structured claim and evidence
PLP-bound human GAD65 catalyzes glutamate decarboxylation to GABA.
Human glutamate decarboxylase 65 / GAD2 → Gamma-aminobutyric acid source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human GAD isoforms; crystallography and enzyme kinetics
exposure
Glutamate turnover in recombinant enzyme assays.
limitations
Recombinant chemistry does not establish a human supplementation response.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Activated B6 helps this enzyme make GABA.
primary_references
[fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 961–971
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GAD isoforms; crystallography and enzyme kinetics · source_derived_draft · unverified_draft
### b6-neuro-gad2-gaba PLP-bound human GAD65 catalyzes glutamate decarboxylation to GABA. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated B6 helps this enzyme make GABA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human GAD isoforms; crystallography and enzyme kinetics limitations: Recombinant chemistry does not establish a human supplementation response. exposure: Glutamate turnover in recombinant enzyme assays. [fenalti-2007-gad] GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop (2007). https://doi.org/10.1038/nsmb1228 DOI: 10.1038/nsmb1228
Complete structured claim and evidence
Recombinant human NAGS catalyzed N-acetylglutamate formation from glutamate and acetyl-CoA.
Human N-acetylglutamate synthase / NAGS → N-Acetyl-L-glutamate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"}
experimental_model
Purified recombinant NAGS kinetics
exposure
Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs
limitations
Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human and mouse enzymes; human findings specified
plain_language
The activator for CPS1 has its own synthesis step.
primary_references
[citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003
tissue_or_cell_type
N-acetylglutamate formation
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 255–266
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant NAGS kinetics · source_derived_draft · unverified_draft
### citrulline-nags-product Recombinant human NAGS catalyzed N-acetylglutamate formation from glutamate and acetyl-CoA. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The activator for CPS1 has its own synthesis step. organism: Human and mouse enzymes; human findings specified tissue_or_cell_type: N-acetylglutamate formation experimental_model: Purified recombinant NAGS kinetics limitations: Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial. exposure: Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs evidence_span: {"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"} [citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003
Complete structured claim and evidence
Arginine approximately doubled the activity of both tested human NAGS constructs.
L-Arginine → Human NAGS catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"}
experimental_model
Purified recombinant NAGS kinetics
exposure
Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs
limitations
Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human and mouse enzymes; human findings specified
plain_language
Arginine can feed back on the upstream nitrogen-disposal pathway.
primary_references
[citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003
tissue_or_cell_type
N-acetylglutamate formation
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 281–292
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant NAGS kinetics · source_derived_draft · unverified_draft
### citrulline-arginine-nags Arginine approximately doubled the activity of both tested human NAGS constructs. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Arginine can feed back on the upstream nitrogen-disposal pathway. organism: Human and mouse enzymes; human findings specified tissue_or_cell_type: N-acetylglutamate formation experimental_model: Purified recombinant NAGS kinetics limitations: Construct-specific kinetics; no human B5-deficiency or arginine-repletion trial. exposure: Glutamate, acetyl-CoA and arginine; mature and conserved-domain constructs evidence_span: {"source_cache": "artifacts/citrulline-research/16321554.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5", "start_char": 0, "end_char": 1498, "text_sha256": "5ce9d57aba8d7973c01de32ab7d5d0287858119fa75f0a372e3ed99523a861a5"} [citrulline-p16321554] Biochemical properties of recombinant human and mouse N-acetylglutamate synthase. (2006). https://pubmed.ncbi.nlm.nih.gov/16321554/ DOI: 10.1016/j.ymgme.2005.10.003
Complete structured claim and evidence
N-acetylglutamate binding reshaped human CPS1 and established the channel linking its two phosphorylation sites.
N-Acetyl-L-glutamate → Human carbamoyl-phosphate synthetase 1 / CPS1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/26592762.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581", "start_char": 0, "end_char": 1079, "text_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581"}
experimental_model
Human recombinant enzyme crystallography and mutation analysis
exposure
Structures without NAG and with NAG plus nucleotides
limitations
Mechanism of enzyme activation; clinical effects of adding nutritional cofactors were not tested.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human CPS1
plain_language
An activator switches the upstream nitrogen-handling enzyme into a functional shape.
primary_references
[citrulline-p26592762] Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26592762/ DOI: 10.1038/srep16950
tissue_or_cell_type
Mitochondrial carbamoyl-phosphate synthesis
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 229–240
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant enzyme crystallography and mutation analysis · source_derived_draft · unverified_draft
### citrulline-cps1-nag N-acetylglutamate binding reshaped human CPS1 and established the channel linking its two phosphorylation sites. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: An activator switches the upstream nitrogen-handling enzyme into a functional shape. organism: Human CPS1 tissue_or_cell_type: Mitochondrial carbamoyl-phosphate synthesis experimental_model: Human recombinant enzyme crystallography and mutation analysis limitations: Mechanism of enzyme activation; clinical effects of adding nutritional cofactors were not tested. exposure: Structures without NAG and with NAG plus nucleotides evidence_span: {"source_cache": "artifacts/citrulline-research/26592762.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581", "start_char": 0, "end_char": 1079, "text_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581"} [citrulline-p26592762] Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26592762/ DOI: 10.1038/srep16950
Complete structured claim and evidence
Human P5CS links glutamate to P5C synthesis through ATP- and NADPH-dependent chemistry.
Human pyrroline-5-carboxylate synthase / ALDH18A1 → Delta-1-pyrroline-5-carboxylate / P5C source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"}
experimental_model
Patient genetics and recombinant variant expression
exposure
ALDH18A1 R84Q compared with wild-type isoforms
limitations
Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human, two siblings and mammalian expression systems
plain_language
This supplies a precursor route connected to ornithine and arginine production.
primary_references
[citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
tissue_or_cell_type
Mitochondrial P5CS and circulating amino acids
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 294–305
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient genetics and recombinant variant expression · source_derived_draft · unverified_draft
### citrulline-p5cs-reaction Human P5CS links glutamate to P5C synthesis through ATP- and NADPH-dependent chemistry. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This supplies a precursor route connected to ornithine and arginine production. organism: Human, two siblings and mammalian expression systems tissue_or_cell_type: Mitochondrial P5CS and circulating amino acids experimental_model: Patient genetics and recombinant variant expression limitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype. exposure: ALDH18A1 R84Q compared with wild-type isoforms evidence_span: {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"} [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
Complete structured claim and evidence
P5CS requires NADPH for its reductive step in glutamate-to-P5C synthesis.
NADPH → Human pyrroline-5-carboxylate synthase / ALDH18A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"}
experimental_model
Patient genetics and recombinant variant expression
exposure
ALDH18A1 R84Q compared with wild-type isoforms
limitations
Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human, two siblings and mammalian expression systems
plain_language
A niacin-derived electron donor participates upstream of citrulline.
primary_references
[citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
tissue_or_cell_type
Mitochondrial P5CS and circulating amino acids
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 307–318
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient genetics and recombinant variant expression · source_derived_draft · unverified_draft
### citrulline-p5cs-nadph P5CS requires NADPH for its reductive step in glutamate-to-P5C synthesis. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A niacin-derived electron donor participates upstream of citrulline. organism: Human, two siblings and mammalian expression systems tissue_or_cell_type: Mitochondrial P5CS and circulating amino acids experimental_model: Patient genetics and recombinant variant expression limitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype. exposure: ALDH18A1 R84Q compared with wild-type isoforms evidence_span: {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"} [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
Complete structured claim and evidence
Purified human cytosolic FPGS used tetrahydrofolate as an effective substrate for polyglutamate synthesis.
Human cytosolic FPGS isoform → Tetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human cytosolic FPGS expressed in bacteria
exposure
Comparative substrate enzyme assays
limitations
Purified substrate preference does not quantify intact-cell flux.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens protein expressed in Escherichia coli
plain_language
FPGS adds tails that help retain usable folate.
primary_references
[chen1996] Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene (1996). https://pubmed.ncbi.nlm.nih.gov/8662720/ DOI: 10.1074/jbc.271.22.13077
tissue_or_cell_type
Purified enzyme
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 255–265
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human cytosolic FPGS expressed in bacteria · source_derived_draft · unverified_draft
### folate-fpgs-thf-substrate Purified human cytosolic FPGS used tetrahydrofolate as an effective substrate for polyglutamate synthesis. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: FPGS adds tails that help retain usable folate. organism: Homo sapiens protein expressed in Escherichia coli tissue_or_cell_type: Purified enzyme experimental_model: Purified human cytosolic FPGS expressed in bacteria limitations: Purified substrate preference does not quantify intact-cell flux. exposure: Comparative substrate enzyme assays [chen1996] Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene (1996). https://pubmed.ncbi.nlm.nih.gov/8662720/ DOI: 10.1074/jbc.271.22.13077
Complete structured claim and evidence
Mitochondrial human FPGS maintained a separately retained mitochondrial folate-polyglutamate pool in reconstituted AUXB1 cells.
Human mitochondrial FPGS isoform → Mitochondrial folate accumulation source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human FPGS isoforms in Chinese hamster AUXB1 cells
exposure
Induced mitochondrial FPGS and fractionation
limitations
Compartment separation is specific to the validated fractionation experiment.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Human enzyme in Cricetulus griseus cells
plain_language
Mitochondria make and keep their own folate tails.
primary_references
[lawrence2014] Mammalian mitochondrial and cytosolic folylpolyglutamate synthetase maintain the subcellular compartmentalization of folates (2014). https://pubmed.ncbi.nlm.nih.gov/25164808/ DOI: 10.1074/jbc.m114.593244
tissue_or_cell_type
AUXB1 mitochondria
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 291–301
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human FPGS isoforms in Chinese hamster AUXB1 cells · source_derived_draft · unverified_draft
### folate-fpgs-mitochondrial-trapping Mitochondrial human FPGS maintained a separately retained mitochondrial folate-polyglutamate pool in reconstituted AUXB1 cells. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondria make and keep their own folate tails. organism: Human enzyme in Cricetulus griseus cells tissue_or_cell_type: AUXB1 mitochondria experimental_model: Human FPGS isoforms in Chinese hamster AUXB1 cells limitations: Compartment separation is specific to the validated fractionation experiment. exposure: Induced mitochondrial FPGS and fractionation [lawrence2014] Mammalian mitochondrial and cytosolic folylpolyglutamate synthetase maintain the subcellular compartmentalization of folates (2014). https://pubmed.ncbi.nlm.nih.gov/25164808/ DOI: 10.1074/jbc.m114.593244
Complete structured claim and evidence
Tracer experiments detected no intact folate-polyglutamate transfer from mitochondria to cytosol in the tested human-FPGS-reconstituted hamster cells.
Folate polyglutamates → Mitochondrial folate polyglutamate export source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human FPGS isoforms in Chinese hamster AUXB1 cells
exposure
Compartment-specific FPGS induction and tracer chase
limitations
Detection-limited result, not proof of universal impermeability.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Human enzyme in Cricetulus griseus cells
plain_language
Stored mitochondrial folates did not measurably replenish the cytosol.
primary_references
[lawrence2014] Mammalian mitochondrial and cytosolic folylpolyglutamate synthetase maintain the subcellular compartmentalization of folates (2014). https://pubmed.ncbi.nlm.nih.gov/25164808/ DOI: 10.1074/jbc.m114.593244
tissue_or_cell_type
AUXB1 mitochondrial and cytosolic fractions
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 303–313
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human FPGS isoforms in Chinese hamster AUXB1 cells · source_derived_draft · unverified_draft
### folate-polyglutamate-no-mito-export Tracer experiments detected no intact folate-polyglutamate transfer from mitochondria to cytosol in the tested human-FPGS-reconstituted hamster cells. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stored mitochondrial folates did not measurably replenish the cytosol. organism: Human enzyme in Cricetulus griseus cells tissue_or_cell_type: AUXB1 mitochondrial and cytosolic fractions experimental_model: Human FPGS isoforms in Chinese hamster AUXB1 cells limitations: Detection-limited result, not proof of universal impermeability. exposure: Compartment-specific FPGS induction and tracer chase [lawrence2014] Mammalian mitochondrial and cytosolic folylpolyglutamate synthetase maintain the subcellular compartmentalization of folates (2014). https://pubmed.ncbi.nlm.nih.gov/25164808/ DOI: 10.1074/jbc.m114.593244
Complete structured claim and evidence
GGCX couples oxidation of reduced vitamin K to conversion of protein-bound glutamate into gamma-carboxyglutamate.
Gamma-glutamyl carboxylase / GGCX → Reduced vitamin K hydroquinone family source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"}
experimental_model
Cryo-EM, binding, cell assays and molecular dynamics
exposure
Apo, osteocalcin-bound and vitamin-K-bound structures
limitations
Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone.
nutrient_topic
Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family
organism
Human GGCX
plain_language
Vitamin K helps an enzyme modify selected proteins; it does not carry calcium into bone itself.
primary_references
[k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
tissue_or_cell_type
Endoplasmic-reticulum membrane enzyme
Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 370–381
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, binding, cell assays and molecular dynamics · source_derived_draft · unverified_draft
### k2-ggcx-cofactor GGCX couples oxidation of reduced vitamin K to conversion of protein-bound glutamate into gamma-carboxyglutamate. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin K helps an enzyme modify selected proteins; it does not carry calcium into bone itself. organism: Human GGCX tissue_or_cell_type: Endoplasmic-reticulum membrane enzyme experimental_model: Cryo-EM, binding, cell assays and molecular dynamics limitations: Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone. exposure: Apo, osteocalcin-bound and vitamin-K-bound structures evidence_span: {"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"} [k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9
Complete structured claim and evidence
Extracellular Mg caused voltage-dependent block of NMDA-type currents in cultured mouse neurons, stronger at hyperpolarized potentials.
Mg2+ → NMDA receptor-mediated current source_derived_draftungraded
Experimental context and source evidence
evidence-system
Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes
experimental_model
Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes
limitations
Native channel subunits were not resolved; no nutritional intake or clinical outcome was tested.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Magnesium restrains this excitatory current in a way that depends on membrane voltage.
primary_references
[nowak-1984-nmda] Magnesium gates glutamate-activated channels in mouse central neurones (1984). https://pubmed.ncbi.nlm.nih.gov/6320006/ DOI: 10.1038/307462a0
tissue
Cultured central neurons
tissue_or_cell_type
Cultured central neurons
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1261–1272
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes · source_derived_draft · unverified_draft
### magnesium-voltage-dependent-nmda-block Extracellular Mg caused voltage-dependent block of NMDA-type currents in cultured mouse neurons, stronger at hyperpolarized potentials. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium restrains this excitatory current in a way that depends on membrane voltage. organism: Mouse tissue_or_cell_type: Cultured central neurons experimental_model: Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes limitations: Native channel subunits were not resolved; no nutritional intake or clinical outcome was tested. evidence-system: Single-channel patch clamp with glutamate/NMDA agonists and extracellular Mg changes tissue: Cultured central neurons [nowak-1984-nmda] Magnesium gates glutamate-activated channels in mouse central neurones (1984). https://pubmed.ncbi.nlm.nih.gov/6320006/ DOI: 10.1038/307462a0
Complete structured claim and evidence
Reconstituted citrin exchanged aspartate for glutamate plus a proton.
Human citrin / SLC25A13 → Mitochondrial aspartate/glutamate exchange source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"}
experimental_model
Reconstituted transporter and transfected-cell assays
exposure
Aspartate exchange for glutamate plus proton; external calcium stimulation
limitations
Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human citrin and aralar proteins
plain_language
Moving aspartate between compartments helps connect nitrogen handling and redox metabolism.
primary_references
[citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
tissue_or_cell_type
Inner mitochondrial membrane transport; malate-aspartate shuttle
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 359–370
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted transporter and transfected-cell assays · source_derived_draft · unverified_draft
### citrulline-citrin-aspartate Reconstituted citrin exchanged aspartate for glutamate plus a proton. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Moving aspartate between compartments helps connect nitrogen handling and redox metabolism. organism: Human citrin and aralar proteins tissue_or_cell_type: Inner mitochondrial membrane transport; malate-aspartate shuttle experimental_model: Reconstituted transporter and transfected-cell assays limitations: Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency. exposure: Aspartate exchange for glutamate plus proton; external calcium stimulation evidence_span: {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"} [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
Complete structured claim and evidence
Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats.
Potassium → GLUD1 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Potassium deprivation changes glutamine nitrogen metabolism and sodium-coupled glutamine transport; these experiments did not manipulate dietary protein adequacy.
endpoint
Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats.
experimental-exposure
Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments.
experimental_model
Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments.
limitations
Dietary deprivation precedes detectable hypokalemia here; protein expression does not independently establish transport flux or quantify net bicarbonate generation.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Rattus norvegicus
plain_language
A second ammonia-producing enzyme increased; this connects glutamate nitrogen to ammonium and its carbon skeleton to 2-oxoglutarate.
primary_references
[hossain-2011-k-ammoniagenesis] Cellular and molecular basis of increased ammoniagenesis in potassium deprivation (2011). https://journals.physiology.org/doi/full/10.1152/ajprenal.00010.2011 DOI: 10.1152/ajprenal.00010.2011
tissue_or_cell_type
renal proximal tubule and whole-kidney excretion
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1000–1012
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. · source_derived_draft · unverified_draft
### k-deprivation-glud1 Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second ammonia-producing enzyme increased; this connects glutamate nitrogen to ammonium and its carbon skeleton to 2-oxoglutarate. organism: Rattus norvegicus tissue_or_cell_type: renal proximal tubule and whole-kidney excretion experimental_model: Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. limitations: Dietary deprivation precedes detectable hypokalemia here; protein expression does not independently establish transport flux or quantify net bicarbonate generation. cross_nutrient: Potassium deprivation changes glutamine nitrogen metabolism and sodium-coupled glutamine transport; these experiments did not manipulate dietary protein adequacy. experimental-exposure: Rats on control or potassium-deficient diets for up to 6 days; NH4Cl co-loading and NRK52E/LLC-PK1 cell experiments. endpoint: Potassium deprivation increased renal glutamate dehydrogenase expression in the studied rats. [hossain-2011-k-ammoniagenesis] Cellular and molecular basis of increased ammoniagenesis in potassium deprivation (2011). https://journals.physiology.org/doi/full/10.1152/ajprenal.00010.2011 DOI: 10.1152/ajprenal.00010.2011
Complete structured claim and evidence
Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule.
Potassium → Glutamine synthetase / GLUL source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
endpoint
Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule.
experimental-exposure
Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
experimental_model
Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
limitations
Expression and localization were measured; the quantitative contribution of GLUL to total flux was not isolated.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Mus musculus
plain_language
Less ammonia-recycling enzyme was present in this compartment, potentially leaving more ammonia available for excretion.
primary_references
[verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
tissue_or_cell_type
renal proximal tubule
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1028–1039
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. · source_derived_draft · unverified_draft
### k-depletion-proximal-glul Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less ammonia-recycling enzyme was present in this compartment, potentially leaving more ammonia available for excretion. organism: Mus musculus tissue_or_cell_type: renal proximal tubule experimental_model: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. limitations: Expression and localization were measured; the quantitative contribution of GLUL to total flux was not isolated. experimental-exposure: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. endpoint: Diet-induced hypokalemia decreased glutamine synthetase expression throughout the mouse proximal tubule. [verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
Complete structured claim and evidence
The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells.
Potassium → Glutamine synthetase / GLUL source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
endpoint
The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells.
experimental-exposure
Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
experimental_model
Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays.
limitations
Cell-specific regulation is not a contradiction of the proximal-tubule result; neither establishes net flux in an intact human kidney.
nutrient_topic
Potassium research collection; topical membership is not evidence of a direct dietary effect. · Potassium
organism
Mus musculus
plain_language
Different kidney cells adjusted the same ammonia-recycling enzyme in opposite directions.
primary_references
[verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
tissue_or_cell_type
type A intercalated cells of cortical and outer medullary collecting duct
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1055–1066
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. · source_derived_draft · unverified_draft
### k-depletion-intercalated-glul The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different kidney cells adjusted the same ammonia-recycling enzyme in opposite directions. organism: Mus musculus tissue_or_cell_type: type A intercalated cells of cortical and outer medullary collecting duct experimental_model: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. limitations: Cell-specific regulation is not a contradiction of the proximal-tubule result; neither establishes net flux in an intact human kidney. experimental-exposure: Mice fed a nominally potassium-free diet for 12 days; renal immunolabeling and protein/RNA assays. endpoint: The same hypokalemic diet increased glutamine synthetase expression in type A intercalated cells. [verlander-2013-gs] Expression of glutamine synthetase in the mouse kidney: localization in multiple epithelial cell types and differential regulation by hypokalemia (2013). https://pubmed.ncbi.nlm.nih.gov/23804452/ DOI: 10.1152/ajprenal.00030.2013
Complete structured claim and evidence
Human recombinant OGDH reacted with 2-oxoglutarate to produce spectroscopic signals supporting a ThDP-bound post-decarboxylation enamine.
Human 2-oxoglutarate dehydrogenase E1 → OGDH-bound carboxypropylidene-ThDP enamine source_derived_draftungraded
Experimental context and source evidence
evidence
[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human OGDH circular dichroism and related spectroscopy.
limitations
Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli.
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
At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants.
primary_references
[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
tissue_or_cell_type
Purified E1
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 842–853
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OGDH circular dichroism and related spectroscopy. · source_derived_draft · unverified_draft
### b1-ogdh-thdp-enamine-chemistry Human recombinant OGDH reacted with 2-oxoglutarate to produce spectroscopic signals supporting a ThDP-bound post-decarboxylation enamine. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants. organism: Homo sapiens tissue_or_cell_type: Purified E1 experimental_model: Human OGDH circular dichroism and related spectroscopy. limitations: Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073
Complete structured claim and evidence
Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.
DLD → Protein-bound reduced dihydrolipoyl-lysine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.
evidence
[{"paper_key": "brautigam-2005-dld", "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
Human DLD crystallography with NAD+ and NADH.
limitations
Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.
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 shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.
primary_references
[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft
### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "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 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
Complete structured claim and evidence

Availability and dependencies

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

Glutamate can be present but unable to enter mitochondria

Condition: machinery_impairment · A human SLC25A22 disease variant abolishes transport in vitro.

Normal role: Cells maintain separate metabolic, extracellular and transmitter glutamate pools through regulated transport, synthesis, recycling and utilization.

Recorded consequence: An intracellular transport bottleneck accompanies severe neonatal neurological disease.