Glycine

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mass spectrometry of mitochondrial tRNAs from depleted cells.

limitations

Detection of an alternative mark does not establish complete functional rescue by glycine.

nutrient_topic

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

plain_language

Low taurine changed the chemical identity of the RNA modification.

primary_references

Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29390138/ · DOI 10.1093/nar/gky068

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 241–247

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mass spectrometry of mitochondrial tRNAs from depleted cells. · source_derived_draft · unverified_draft

## taurine-glycine-substitution Low taurine changed the chemical identity of the RNA modification. Taurine-depleted cultured cells accumulated mitochondrial tRNA cmnm5U, whose glycine-derived group replaces the taurine-derived group of tau-m5U. Model: Mass spectrometry of mitochondrial tRNAs from depleted cells. Limitations: Detection of an alternative mark does not establish complete functional rescue by glycine. Evidence access: Primary abstract Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29390138/ · DOI 10.1093/nar/gky068

evidence_access

Primary full text

experimental_model

Bovine articular chondrocyte monolayers; 15-day concentration series and collagen ELISA.

limitations

The paper proposes dietary implications, but the experiment does not establish human glycine essentiality, osteoarthritis causation or cartilage regeneration.

nutrient_topic

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

plain_language

Collagen-producing cells responded to extra glycine in a culture assay.

primary_references

High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30006659/ · DOI 10.1007/s00726-018-2611-x

Glycine: supply, one-carbon allocation, receptors 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 · Bovine articular chondrocyte monolayers; 15-day concentration series and collagen ELISA. · source_derived_draft · unverified_draft

## glycine-collagen-culture Collagen-producing cells responded to extra glycine in a culture assay. Increasing medium glycine from the millimolar range increased type-II collagen production in cultured bovine chondrocytes, with larger sustained effects than the tested proline/lysine increments. Model: Bovine articular chondrocyte monolayers; 15-day concentration series and collagen ELISA. Limitations: The paper proposes dietary implications, but the experiment does not establish human glycine essentiality, osteoarthritis causation or cartilage regeneration. Evidence access: Primary full text High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30006659/ · DOI 10.1007/s00726-018-2611-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Zebrafish Slc25a38-deficiency model with supplementation.

limitations

Species, folate synthesis and exposure differ from yeast; a context difference is not a fabricated contradiction.

nutrient_topic

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

plain_language

The single-ingredient rescue did not transfer from yeast to this animal model.

primary_references

Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26821380/ · DOI 10.1371/journal.pgen.1005783

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Zebrafish Slc25a38-deficiency model with supplementation. · source_derived_draft · unverified_draft

## glycine-fish-glycine-alone The single-ingredient rescue did not transfer from yeast to this animal model. Glycine alone did not restore hemoglobin in the zebrafish Slc25a38 congenital-sideroblastic-anemia model. Model: Zebrafish Slc25a38-deficiency model with supplementation. Limitations: Species, folate synthesis and exposure differ from yeast; a context difference is not a fabricated contradiction. Evidence access: Primary full text Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26821380/ · DOI 10.1371/journal.pgen.1005783

evidence_access

Primary abstract

experimental_model

Cancer cultures deprived of serine, glycine exposure and metabolic analysis.

limitations

No exposure threshold for humans is derived; one-carbon depletion is the pathway interpretation supported by the rescue experiment.

nutrient_topic

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

plain_language

Using glycine to rebuild missing serine can draw from the folate carbon pool.

primary_references

Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24813884/ · DOI 10.1016/j.celrep.2014.04.045

Glycine: supply, one-carbon allocation, receptors 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 · Cancer cultures deprived of serine, glycine exposure and metabolic analysis. · source_derived_draft · unverified_draft

## glycine-glycine-reverse-flux Using glycine to rebuild missing serine can draw from the folate carbon pool. With serine absent, higher glycine concentrations inhibited growth and glycine was converted to serine, a reaction consuming one-carbon units. Model: Cancer cultures deprived of serine, glycine exposure and metabolic analysis. Limitations: No exposure threshold for humans is derived; one-carbon depletion is the pathway interpretation supported by the rescue experiment. Evidence access: Primary abstract Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24813884/ · DOI 10.1016/j.celrep.2014.04.045

evidence_access

Primary abstract

experimental_model

Human recombinant receptor comparison using high agonist concentrations.

limitations

Not equivalent to relative sedative potency after oral intake.

nutrient_topic

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

plain_language

Related molecules activate the same receptor with different timing.

primary_references

Kinetic determinants of agonist action at the recombinant human glycine receptor. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12679369/ · DOI 10.1113/jphysiol.2002.037796

Glycine: supply, one-carbon allocation, receptors 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 recombinant receptor comparison using high agonist concentrations. · source_derived_draft · unverified_draft

## glycine-glyr-ligand-kinetics Related molecules activate the same receptor with different timing. At saturating 30 mM agonist, human alpha1 glycine-receptor activation rose faster with glycine than beta-alanine or taurine, and glycine responses decayed more slowly after removal. Model: Human recombinant receptor comparison using high agonist concentrations. Limitations: Not equivalent to relative sedative potency after oral intake. Evidence access: Primary abstract Kinetic determinants of agonist action at the recombinant human glycine receptor. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12679369/ · DOI 10.1113/jphysiol.2002.037796

evidence_access

Primary abstract

experimental_model

Human alpha1 receptor, rapid agonist application and patch recording.

limitations

Homomeric experimental receptor differs from native heteromeric receptor mixtures; chloride gradient determines current consequences.

nutrient_topic

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

plain_language

Glycine can directly open a receptor channel.

primary_references

Kinetic determinants of agonist action at the recombinant human glycine receptor. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12679369/ · DOI 10.1113/jphysiol.2002.037796

Glycine: supply, one-carbon allocation, receptors 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 alpha1 receptor, rapid agonist application and patch recording. · source_derived_draft · unverified_draft

## glycine-glyr-opening Glycine can directly open a receptor channel. Glycine opened recombinant human alpha1 homomeric glycine receptors in HEK293 cells; rapid-application and single-channel assays resolved activation kinetics. Model: Human alpha1 receptor, rapid agonist application and patch recording. Limitations: Homomeric experimental receptor differs from native heteromeric receptor mixtures; chloride gradient determines current consequences. Evidence access: Primary abstract Kinetic determinants of agonist action at the recombinant human glycine receptor. · 2003 · https://pubmed.ncbi.nlm.nih.gov/12679369/ · DOI 10.1113/jphysiol.2002.037796

evidence_access

Primary full text

experimental_model

Recombinant GPR158 in HEK293-derived membrane binding assays.

limitations

Construct species is not resolved by the accessed main-text methods; human host cells do not establish human receptor sequence. Binding Kd is not an oral dose.

nutrient_topic

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

plain_language

Glycine has a receptor beyond its familiar chloride channel and NMDA site.

primary_references

Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

Glycine: supply, one-carbon allocation, receptors 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 · Recombinant GPR158 in HEK293-derived membrane binding assays. · source_derived_draft · unverified_draft

## glycine-gpr158-binding Glycine has a receptor beyond its familiar chloride channel and NMDA site. Radioligand binding and mutagenesis supported direct glycine recognition by the GPR158 Cache domain, with an estimated binding Kd near 3 micromolar in receptor-expressing membranes. Model: Recombinant GPR158 in HEK293-derived membrane binding assays. Limitations: Construct species is not resolved by the accessed main-text methods; human host cells do not establish human receptor sequence. Binding Kd is not an oral dose. Evidence access: Primary full text Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

evidence_access

Primary full text

experimental_model

Male C57BL/6J mice aged four to six weeks; slice patch clamp with synaptic blockers.

limitations

Authors attributed the response to GPR158; pharmacology alone is weaker than a receptor-knockout test and does not prove direct channel binding.

nutrient_topic

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

plain_language

Glycine-sensitive signaling intersects with potassium-channel control of firing.

primary_references

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w

Glycine: supply, one-carbon allocation, receptors 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 · Male C57BL/6J mice aged four to six weeks; slice patch clamp with synaptic blockers. · source_derived_draft · unverified_draft

## glycine-gpr158-potassium-current Glycine-sensitive signaling intersects with potassium-channel control of firing. In mouse accumbens slices, 1 mM glycine increased medium-spiny-neuron firing and reduced M-current amplitude; a selective M-current inhibitor mimicked and occluded the response. Model: Male C57BL/6J mice aged four to six weeks; slice patch clamp with synaptic blockers. Limitations: Authors attributed the response to GPR158; pharmacology alone is weaker than a receptor-knockout test and does not prove direct channel binding. Evidence access: Primary full text Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w

evidence_access

Primary full text

experimental_model

Recombinant cellular BRET assays, including 100 micromolar glycine comparisons.

limitations

Functional coupling does not prove every intervening conformational step or a clinical mood effect.

nutrient_topic

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

plain_language

Receptor binding changes how quickly another signaling switch is turned off.

primary_references

Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

Glycine: supply, one-carbon allocation, receptors 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 · Recombinant cellular BRET assays, including 100 micromolar glycine comparisons. · source_derived_draft · unverified_draft

## glycine-gpr158-rgs-inhibition Receptor binding changes how quickly another signaling switch is turned off. Glycine slowed G-alpha-o deactivation only when GPR158 was coexpressed with RGS7/G-beta5, supporting inhibition of the complex's GTPase-accelerating activity. Model: Recombinant cellular BRET assays, including 100 micromolar glycine comparisons. Limitations: Functional coupling does not prove every intervening conformational step or a clinical mood effect. Evidence access: Primary full text Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Yeast hem25 deletion with glycine or 5-aminolevulinate supplementation.

limitations

Yeast has alternative pathways and synthesizes folate; this is not a human treatment result.

nutrient_topic

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

plain_language

Extra substrate bypassed part of a transport bottleneck in yeast.

primary_references

Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26821380/ · DOI 10.1371/journal.pgen.1005783

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Yeast hem25 deletion with glycine or 5-aminolevulinate supplementation. · source_derived_draft · unverified_draft

## glycine-hem25-glycine-rescue Extra substrate bypassed part of a transport bottleneck in yeast. Supplementing 5 mM glycine restored heme levels in yeast lacking Hem25 in the reported experiment. Model: Yeast hem25 deletion with glycine or 5-aminolevulinate supplementation. Limitations: Yeast has alternative pathways and synthesizes folate; this is not a human treatment result. Evidence access: Primary full text Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26821380/ · DOI 10.1371/journal.pgen.1005783

evidence_access

Primary full text

experimental_model

GLYAT/GLYATL1 enzyme experiments.

limitations

Not evidence that glycine treatment never works in isovaleric acidemia; substrate, enzyme and kinetic context matter.

nutrient_topic

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

plain_language

Adding substrate did not keep increasing this disposal reaction.

primary_references

The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36817957/ · DOI 10.1016/j.csbj.2023.01.041

Glycine: supply, one-carbon allocation, receptors 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 · GLYAT/GLYATL1 enzyme experiments. · source_derived_draft · unverified_draft

## glycine-isovaleryl-glycine-limit Adding substrate did not keep increasing this disposal reaction. Increasing glycine did not increase N-isovalerylglycine formation in the reported in-vitro conjugation experiments. Model: GLYAT/GLYATL1 enzyme experiments. Limitations: Not evidence that glycine treatment never works in isovaleric acidemia; substrate, enzyme and kinetic context matter. Evidence access: Primary full text The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36817957/ · DOI 10.1016/j.csbj.2023.01.041

evidence_access

Primary abstract

experimental_model

Rat Kupffer-cell culture with glycine, LPS and receptor pharmacology.

limitations

High in-vitro exposure; not a demonstrated systemic anti-inflammatory effect in humans.

nutrient_topic

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

plain_language

Glycine changed a calcium signal in liver immune cells.

primary_references

Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

Glycine: supply, one-carbon allocation, receptors 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 · Rat Kupffer-cell culture with glycine, LPS and receptor pharmacology. · source_derived_draft · unverified_draft

## glycine-kupffer-calcium Glycine changed a calcium signal in liver immune cells. Glycine at 1 mM nearly prevented the calcium rise elicited by 10 micrograms/mL LPS in cultured rat Kupffer cells. Model: Rat Kupffer-cell culture with glycine, LPS and receptor pharmacology. Limitations: High in-vitro exposure; not a demonstrated systemic anti-inflammatory effect in humans. Evidence access: Primary abstract Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

evidence_access

Primary abstract

experimental_model

Rat cell-culture LPS challenge.

limitations

The cell assay does not establish a clinical effect or prove all intermediary steps.

nutrient_topic

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

plain_language

A signaling change accompanied lower inflammatory-mediator output.

primary_references

Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

Glycine: supply, one-carbon allocation, receptors 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 · Rat cell-culture LPS challenge. · source_derived_draft · unverified_draft

## glycine-kupffer-tnf A signaling change accompanied lower inflammatory-mediator output. Glycine reduced LPS-associated TNF-alpha production in cultured rat Kupffer cells. Model: Rat cell-culture LPS challenge. Limitations: The cell assay does not establish a clinical effect or prove all intermediary steps. Evidence access: Primary abstract Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

evidence_access

Primary full text

experimental_model

Human monocyte-derived macrophages, LPS/nigericin, native-protein analysis and knockdown.

limitations

Direct or indirect target engagement remains unresolved; 50 mM bath exposure is not a dietary plasma concentration.

nutrient_topic

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

plain_language

The membrane effect also occurred in human cells at a much higher experimental exposure.

primary_references

Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

Glycine: supply, one-carbon allocation, receptors 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 monocyte-derived macrophages, LPS/nigericin, native-protein analysis and knockdown. · source_derived_draft · unverified_draft

## glycine-ninj1-human-clustering The membrane effect also occurred in human cells at a much higher experimental exposure. In primary human macrophages, 50 mM glycine inhibited pyroptosis-associated NINJ1 clustering and membrane rupture; NINJ1 knockdown produced a similar rupture phenotype. Model: Human monocyte-derived macrophages, LPS/nigericin, native-protein analysis and knockdown. Limitations: Direct or indirect target engagement remains unresolved; 50 mM bath exposure is not a dietary plasma concentration. Evidence access: Primary full text Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

evidence_access

Primary full text

experimental_model

Mouse iBMDM knockout and glycine comparisons; stimulus-specific exposure durations.

limitations

No-additivity supports a shared process, not proof of direct glycine binding to NINJ1.

nutrient_topic

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

plain_language

A late membrane-rupture step was inhibited across several injury models.

primary_references

Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

Glycine: supply, one-carbon allocation, receptors 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 · Mouse iBMDM knockout and glycine comparisons; stimulus-specific exposure durations. · source_derived_draft · unverified_draft

## glycine-ninj1-mouse A late membrane-rupture step was inhibited across several injury models. Glycine at 5 mM reduced LDH release in mouse macrophages undergoing tested pyroptotic, necrotic and post-apoptotic lysis, with no additional protection in Ninj1-knockout cells. Model: Mouse iBMDM knockout and glycine comparisons; stimulus-specific exposure durations. Limitations: No-additivity supports a shared process, not proof of direct glycine binding to NINJ1. Evidence access: Primary full text Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

evidence_access

Primary full text

experimental_model

Primary human macrophages under a defined necroptosis protocol.

limitations

Different death execution pathways explain a context boundary; do not label this a conflicting replication of pyroptosis.

nutrient_topic

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

plain_language

The same protection did not apply to every route of cell death.

primary_references

Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

Glycine: supply, one-carbon allocation, receptors 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 · Primary human macrophages under a defined necroptosis protocol. · source_derived_draft · unverified_draft

## glycine-ninj1-necroptosis-limit The same protection did not apply to every route of cell death. Glycine did not protect primary human macrophages from the tested zVAD/BV6/TNF-induced necroptotic rupture. Model: Primary human macrophages under a defined necroptosis protocol. Limitations: Different death execution pathways explain a context boundary; do not label this a conflicting replication of pyroptosis. Evidence access: Primary full text Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

evidence_access

Primary full text

experimental_model

Primary human macrophage energy/viability measurements alongside LDH assays.

limitations

The outcome is suppression of rupture, not reversal of upstream cell death.

nutrient_topic

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

plain_language

An intact membrane did not mean the cell survived.

primary_references

Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

Glycine: supply, one-carbon allocation, receptors 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 · Primary human macrophage energy/viability measurements alongside LDH assays. · source_derived_draft · unverified_draft

## glycine-ninj1-viability-limit An intact membrane did not mean the cell survived. Human pyroptotic macrophages protected from rupture by glycine still lost mitochondrial membrane potential and ATP. Model: Primary human macrophage energy/viability measurements alongside LDH assays. Limitations: The outcome is suppression of rupture, not reversal of upstream cell death. Evidence access: Primary full text Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36468682/ · DOI 10.7554/eLife.78609

evidence_access

Primary full text

experimental_model

Human LOX IMVI and A498 cancer cultures; positional isotope tracing.

limitations

This experiment does not measure glycine-cleavage flux in every cell type.

nutrient_topic

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

plain_language

An amino acid can supply part of a DNA/RNA building block directly.

primary_references

Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595

Glycine: supply, one-carbon allocation, receptors 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 · Human LOX IMVI and A498 cancer cultures; positional isotope tracing. · source_derived_draft · unverified_draft

## glycine-purine-incorporation An amino acid can supply part of a DNA/RNA building block directly. Carbon-labeled glycine entered purine nucleotides in LOX IMVI cells; positional tracing supported direct glycine incorporation rather than glycine-cleavage-derived one-carbon incorporation in that setting. Model: Human LOX IMVI and A498 cancer cultures; positional isotope tracing. Limitations: This experiment does not measure glycine-cleavage flux in every cell type. Evidence access: Primary full text Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595

evidence_access

Primary abstract

experimental_model

Primary cancer-cell nutrient-restriction and metabolic tracing study.

limitations

Abstract-level extraction; model-specific result does not negate glycine-dependent growth in other culture conditions.

nutrient_topic

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

plain_language

The ability to interconvert two amino acids does not make their supplies interchangeable.

primary_references

Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24813884/ · DOI 10.1016/j.celrep.2014.04.045

Glycine: supply, one-carbon allocation, receptors 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 · Primary cancer-cell nutrient-restriction and metabolic tracing study. · source_derived_draft · unverified_draft

## glycine-serine-required-context The ability to interconvert two amino acids does not make their supplies interchangeable. In the tested cancer cultures, exogenous glycine did not replace serine for nucleotide synthesis and proliferation; glycine restriction or glycine-cleavage depletion did not impede growth. Model: Primary cancer-cell nutrient-restriction and metabolic tracing study. Limitations: Abstract-level extraction; model-specific result does not negate glycine-dependent growth in other culture conditions. Evidence access: Primary abstract Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24813884/ · DOI 10.1016/j.celrep.2014.04.045

evidence_access

Primary full text

experimental_model

Ten male company employees enrolled, seven analyzed; 25% sleep restriction for three nights, glycine or placebo 30 minutes before bed.

limitations

Small selected sample, short duration and industry setting limit generalization; rat SCN experiments do not prove the human mechanism.

nutrient_topic

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

plain_language

A small human experiment measured next-day performance rather than proving a molecular pathway.

primary_references

The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22529837/ · DOI 10.3389/fneur.2012.00061

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 426–432

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ten male company employees enrolled, seven analyzed; 25% sleep restriction for three nights, glycine or placebo 30 minutes before bed. · source_derived_draft · unverified_draft

## glycine-sleep-human-outcomes A small human experiment measured next-day performance rather than proving a molecular pathway. In a randomized single-blind crossover study analyzing seven healthy men after partial sleep restriction, 3 g bedtime glycine improved reported fatigue and psychomotor vigilance measures. Model: Ten male company employees enrolled, seven analyzed; 25% sleep restriction for three nights, glycine or placebo 30 minutes before bed. Limitations: Small selected sample, short duration and industry setting limit generalization; rat SCN experiments do not prove the human mechanism. Evidence access: Primary full text The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22529837/ · DOI 10.3389/fneur.2012.00061

evidence_access

Primary abstract

experimental_model

Rat oral, intracerebral and SCN-ablation experiments.

limitations

The routes are not interchangeable; abstract-level extraction does not establish the human mediation mechanism.

nutrient_topic

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

plain_language

A brain circuit connected the amino-acid intervention with body heat loss.

primary_references

The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533534/ · DOI 10.1038/npp.2014.326

Glycine: supply, one-carbon allocation, receptors 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 · Rat oral, intracerebral and SCN-ablation experiments. · source_derived_draft · unverified_draft

## glycine-sleep-rat-scn A brain circuit connected the amino-acid intervention with body heat loss. Glycine increased cutaneous blood flow and promoted sleep in the rat experiments; SCN ablation abolished the reported sleep-promoting and hypothermic responses. Model: Rat oral, intracerebral and SCN-ablation experiments. Limitations: The routes are not interchangeable; abstract-level extraction does not establish the human mediation mechanism. Evidence access: Primary abstract The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533534/ · DOI 10.1038/npp.2014.326

evidence_access

Primary abstract

experimental_model

Rat neuronal electrophysiological assay.

limitations

An assay co-agonist effect does not show that glycine supplements change human disease outcomes.

nutrient_topic

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

plain_language

A second amino acid changed how strongly the metabolite blocked a receptor.

primary_references

The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11567036/ · DOI 10.1523/JNEUROSCI.21-19-07463.2001

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 314–320

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Rat neuronal electrophysiological assay. · source_derived_draft · unverified_draft

## tryptophan-glycine-kyna-nmda A second amino acid changed how strongly the metabolite blocked a receptor. Kynurenic-acid NMDA-blocking IC50 shifted from about 15 to 235 micromolar when 10 micromolar glycine was present. Model: Rat neuronal electrophysiological assay. Limitations: An assay co-agonist effect does not show that glycine supplements change human disease outcomes. Evidence access: Primary abstract The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11567036/ · DOI 10.1523/JNEUROSCI.21-19-07463.2001

evidence_access

Primary abstract

experimental_model

Biochemical assays, primary cultures and mouse microdialysis; Asc-1 knockout abolished the release response.

limitations

Inhibition of synthesis and stimulation of release are distinct endpoints, not contradictory directions for one reaction.

nutrient_topic

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

plain_language

The same neighboring amino acid can affect both production and release in different ways.

primary_references

The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 358–364

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical assays, primary cultures and mouse microdialysis; Asc-1 knockout abolished the release response. · source_derived_draft · unverified_draft

## l-serine-glycine-racemase The same neighboring amino acid can affect both production and release in different ways. Intracellular glycine tonically inhibited serine racemase in the study, while glycine exposure could transiently promote D-serine release through Asc-1. Model: Biochemical assays, primary cultures and mouse microdialysis; Asc-1 knockout abolished the release response. Limitations: Inhibition of synthesis and stimulation of release are distinct endpoints, not contradictory directions for one reaction. Evidence access: Primary abstract The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116

evidence_access

Primary abstract

experimental_model

Heterologous receptor transport assays.

limitations

Requirement is for receptor activation, not evidence for an oral supplement combination.

nutrient_topic

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

plain_language

Other amino acids gate this entry route.

primary_references

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

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 454–460

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

## spermidine-nmda-ligands Other amino acids gate this entry route. Spermidine uptake through the tested NMDA receptors required glycine and glutamate. Model: Heterologous receptor transport assays. Limitations: Requirement is for receptor activation, not evidence for an oral supplement combination. Evidence access: Primary abstract Spermidine and Ca(2+), but not Na(+), can permeate NMDA receptors consisting of GluN1 and GluN2A or GluN2B in the presence of Mg(2+). · 2015 · https://pubmed.ncbi.nlm.nih.gov/26086092/ · DOI 10.1016/j.bbrc.2015.06.081

evidence_access

Primary abstract

experimental_model

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

cross_nutrient

Handoff to existing PLP-dependent glycine decarboxylase and lipoyl-GCSH/AMT folate transfer evidence; not new deficiency evidence.

experimental_model

Radiolabeled mitochondrial flux assay

exposure

Assay conditions described in the linked primary study.

limitations

No B6 or lipoate dietary perturbation tested.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Mus musculus

plain_language

Glycine cleavage can feed folate-bound carbon into mitochondrial formate production.

primary_references

[pike-2010] Mitochondrial C1-tetrahydrofolate synthase (MTHFD1L) supports the flow of mitochondrial one-carbon units into the methyl cycle in embryos (2010). https://pubmed.ncbi.nlm.nih.gov/19948730/ DOI: 10.1074/jbc.m109.079855

tissue_or_cell_type

Embryonic mitochondria

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1096–1107

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled mitochondrial flux assay · source_derived_draft · unverified_draft

### embryonic-glycine-formate Isolated mouse embryonic mitochondria converted labeled glycine carbon into formate. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glycine cleavage can feed folate-bound carbon into mitochondrial formate production. organism: Mus musculus tissue_or_cell_type: Embryonic mitochondria experimental_model: Radiolabeled mitochondrial flux assay limitations: No B6 or lipoate dietary perturbation tested. exposure: Assay conditions described in the linked primary study. cross_nutrient: Handoff to existing PLP-dependent glycine decarboxylase and lipoyl-GCSH/AMT folate transfer evidence; not new deficiency evidence. [pike-2010] Mitochondrial C1-tetrahydrofolate synthase (MTHFD1L) supports the flow of mitochondrial one-carbon units into the methyl cycle in embryos (2010). https://pubmed.ncbi.nlm.nih.gov/19948730/ DOI: 10.1074/jbc.m109.079855

cross_nutrient

PLP chemistry connects with the lipoyl component of glycine cleavage.

experimental_model

Purified chicken liver mitochondrial P-protein

limitations

Free lipoic acid assay; not evidence that supplements replace the intact cleavage system.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Gallus gallus

plain_language

B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners.

primary_references

[b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5

tissue_or_cell_type

Chicken liver mitochondrial protein

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 659–669

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chicken liver mitochondrial P-protein · source_derived_draft · unverified_draft

### b6-met-chicken-gldc-decarboxylation Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners. organism: Gallus gallus tissue_or_cell_type: Chicken liver mitochondrial protein experimental_model: Purified chicken liver mitochondrial P-protein limitations: Free lipoic acid assay; not evidence that supplements replace the intact cleavage system. cross_nutrient: PLP chemistry connects with the lipoyl component of glycine cleavage. [b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5

evidence_access

Primary full text

experimental_model

Human transporter in nonhuman COS-7 host cells; whole-cell electrophysiology, usually 1 mM glycine.

limitations

The stoichiometry is established background incorporated into this primary kinetic study; no dietary salt intervention. Human protein and host-cell species differ.

nutrient_topic

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

plain_language

Glycine uptake draws on ion gradients, not just the amount of amino acid outside.

primary_references

A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

transport_effect

raises Sodium- and chloride-coupled glycine transport, which is inward.

transport_pool

the expressing cell Sodium- and chloride-coupled glycine transport, which is inward.

Glycine: supply, one-carbon allocation, receptors 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 transporter in nonhuman COS-7 host cells; whole-cell electrophysiology, usually 1 mM glycine. · source_derived_draft · unverified_draft

## glycine-glyt1-transport Glycine uptake draws on ion gradients, not just the amount of amino acid outside. Human GlyT1 expressed in COS-7 cells transported glycine with sodium and chloride; the kinetic analysis used the established 2 Na+:1 Cl-:1 glycine coupling. Model: Human transporter in nonhuman COS-7 host cells; whole-cell electrophysiology, usually 1 mM glycine. Limitations: The stoichiometry is established background incorporated into this primary kinetic study; no dietary salt intervention. Human protein and host-cell species differ. Evidence access: Primary full text A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

evidence_access

Primary full text

experimental_model

Human recombinant GlyT2, voltage clamp and kinetic modeling.

limitations

Methods refer to GlyT2a and a purchased GlyT2b plasmid; this record stays at gene level rather than resolving that isoform discrepancy by guesswork.

nutrient_topic

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

plain_language

A second transporter uses a different ion coupling to accumulate the same substrate.

primary_references

A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

transport_effect

raises Recorded as sodium/chloride-coupled glycine uptake.

transport_pool

the expressing cell Recorded as sodium/chloride-coupled glycine uptake.

Glycine: supply, one-carbon allocation, receptors 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 recombinant GlyT2, voltage clamp and kinetic modeling. · source_derived_draft · unverified_draft

## glycine-glyt2-transport A second transporter uses a different ion coupling to accumulate the same substrate. Human GlyT2 expressed in COS-7 cells supported sodium/chloride-coupled glycine uptake; the study modeled its established 3 Na+:1 Cl-:1 glycine stoichiometry. Model: Human recombinant GlyT2, voltage clamp and kinetic modeling. Limitations: Methods refer to GlyT2a and a purchased GlyT2b plasmid; this record stays at gene level rather than resolving that isoform discrepancy by guesswork. Evidence access: Primary full text A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

evidence_access

Primary abstract

experimental_model

Human/yeast carrier biochemistry and yeast genetic complementation.

limitations

Primary abstract access; later PLP-homeostasis findings broaden interpretation. This claim does not establish exclusive substrate specificity.

nutrient_topic

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

plain_language

A mitochondrial carrier connects access to glycine with heme production.

primary_references

Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27476175/ · DOI 10.1074/jbc.M116.736876

transport_effect

raises Human expression complemented heme-pathway defects in yeast lacking Hem25, which is matrix glycine supply.

transport_pool

the mitochondrial matrix Human expression complemented heme-pathway defects in yeast lacking Hem25, which is matrix glycine supply.

Glycine: supply, one-carbon allocation, receptors 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/yeast carrier biochemistry and yeast genetic complementation. · source_derived_draft · unverified_draft

## glycine-s38-glycine-transport A mitochondrial carrier connects access to glycine with heme production. The biochemical characterization reported glycine transport by human SLC25A38; human SLC25A38 expression complemented heme-pathway defects in yeast lacking Hem25. Model: Human/yeast carrier biochemistry and yeast genetic complementation. Limitations: Primary abstract access; later PLP-homeostasis findings broaden interpretation. This claim does not establish exclusive substrate specificity. Evidence access: Primary abstract Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27476175/ · DOI 10.1074/jbc.M116.736876

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse genetic deletion with extracellular amino-acid measurements and electrophysiology.

limitations

This does not show that oral proline treats NMDAR dysfunction in humans. Correction record: Author correction PMID 39242973 / DOI 10.1038/s44321-024-00125-y corrects the human embryonic stem-cell neuron protocol IRB approval number to KH2017-109 from KA2018-61 and KH2020-55. It does not report a change to experimental results. https://link.springer.com/article/10.1038/s44321-024-00125-y

nutrient_topic

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

plain_language

Changing a proline-sharing transporter can change glycine-dependent brain signaling.

primary_references

SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33428810/ · DOI 10.15252/emmm.202012632

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 206–212

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic deletion with extracellular amino-acid measurements and electrophysiology. · source_derived_draft · unverified_draft

## l-proline-brain-transporter-loss Changing a proline-sharing transporter can change glycine-dependent brain signaling. Slc6a20a-knockout mice had higher extracellular brain glycine and increased NMDA-receptor currents. Model: Mouse genetic deletion with extracellular amino-acid measurements and electrophysiology. Limitations: This does not show that oral proline treats NMDAR dysfunction in humans. Correction record: Author correction PMID 39242973 / DOI 10.1038/s44321-024-00125-y corrects the human embryonic stem-cell neuron protocol IRB approval number to KH2017-109 from KA2018-61 and KH2020-55. It does not report a change to experimental results. https://link.springer.com/article/10.1038/s44321-024-00125-y Evidence access: Primary full text SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33428810/ · DOI 10.15252/emmm.202012632

evidence_access

Primary full text

experimental_model

Human SIT1 in Xenopus oocytes; 1 mM substrates at pH 7.4 and -60 mV.

limitations

Failure of glycine to stabilize purified SIT1 thermally did not rule out its transport; binding-proxy and transport assays measure different things.

nutrient_topic

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

plain_language

This transporter has overlapping amino-acid routes with unequal efficiency.

primary_references

Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38951531/ · DOI 10.1038/s41467-024-48921-x

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 190–196

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SIT1 in Xenopus oocytes; 1 mM substrates at pH 7.4 and -60 mV. · source_derived_draft · unverified_draft

## l-proline-sit1-glycine This transporter has overlapping amino-acid routes with unequal efficiency. Human SIT1 produced glycine-evoked current about 18% of the proline response in the reported substrate comparison; sarcosine current was about 83%. Model: Human SIT1 in Xenopus oocytes; 1 mM substrates at pH 7.4 and -60 mV. Limitations: Failure of glycine to stabilize purified SIT1 thermally did not rule out its transport; binding-proxy and transport assays measure different things. Evidence access: Primary full text Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38951531/ · DOI 10.1038/s41467-024-48921-x

evidence_access

Primary abstract

experimental_model

Four-hour labeled-threonine/glycine infusions under control and high-threonine diets.

limitations

The paper called this TDG flux before the human TDH pseudogene was characterized. Retain the tracer observation without asserting functional human TDH; alternative routes were not resolved.

nutrient_topic

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

plain_language

Detecting carbon transfer does not identify the enzyme responsible.

primary_references

Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10780944/ · DOI 10.1152/ajpendo.2000.278.5.E877

L-Threonine: translation, intestinal barrier, metabolism 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 · Four-hour labeled-threonine/glycine infusions under control and high-threonine diets. · source_derived_draft · unverified_draft

## l-threonine-human-glycine-tracer Detecting carbon transfer does not identify the enzyme responsible. A study in six adult men detected limited threonine-derived glycine labeling, accounting for an estimated 7–11% of threonine catabolism under its model. Model: Four-hour labeled-threonine/glycine infusions under control and high-threonine diets. Limitations: The paper called this TDG flux before the human TDH pseudogene was characterized. Retain the tracer observation without asserting functional human TDH; alternative routes were not resolved. Evidence access: Primary abstract Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10780944/ · DOI 10.1152/ajpendo.2000.278.5.E877

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human patient fibroblast assays plus expression validation.

limitations

Single-patient mechanistic discovery does not determine severity for all screen-detected variants.

nutrient_topic

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

plain_language

A breakdown block can be detected through an alternative excreted product.

primary_references

Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11013134/ · DOI 10.1086/303105

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Isoleucine: transport, translation, catabolism 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 fibroblast assays plus expression validation. · source_derived_draft · unverified_draft

## isoleucine-acadsb-loss A breakdown block can be detected through an alternative excreted product. An ACADSB splice defect caused exon skipping, impaired 2-methylbutyryl-CoA oxidation and isolated 2-methylbutyrylglycinuria in the reported patient. Model: Human patient fibroblast assays plus expression validation. Limitations: Single-patient mechanistic discovery does not determine severity for all screen-detected variants. Evidence access: Primary abstract Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11013134/ · DOI 10.1086/303105

evidence_access

Primary abstract

experimental_model

Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate.

limitations

Cofactor cycling is not evidence that B6 is irreversibly consumed once per reaction.

nutrient_topic

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

plain_language

The B6 cofactor changes form while helping transfer nitrogen.

primary_references

Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 40–46

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate. · source_derived_draft · unverified_draft

## alanine-agt-pmp-cycle The B6 cofactor changes form while helping transfer nitrogen. Pre-steady-state analysis of human AGXT showed that PMP remained bound during its catalytic cycle and the AGXT–PMP complex reacted efficiently with oxo-acid substrates. Model: Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate. Limitations: Cofactor cycling is not evidence that B6 is irreversibly consumed once per reaction. Evidence access: Primary abstract Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637

evidence_access

Primary abstract

experimental_model

Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays.

limitations

Peroxisomal enzyme identity does not mean intracellular flux or supplement benefit was measured.

nutrient_topic

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

plain_language

Alanine supplies an amino group that turns glyoxylate into glycine.

primary_references

Construction, purification and characterization of untagged human liver alanine-glyoxylate aminotransferase expressed in Escherichia coli. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18289107/ · DOI 10.2174/092986608783489580

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 32–38

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays. · source_derived_draft · unverified_draft

## alanine-agt-reaction Alanine supplies an amino group that turns glyoxylate into glycine. Purified untagged human AGXT catalyzed the PLP-dependent reaction alanine + glyoxylate ⇌ pyruvate + glycine; forward and reverse kinetic parameters were measured. Model: Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays. Limitations: Peroxisomal enzyme identity does not mean intracellular flux or supplement benefit was measured. Evidence access: Primary abstract Construction, purification and characterization of untagged human liver alanine-glyoxylate aminotransferase expressed in Escherichia coli. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18289107/ · DOI 10.2174/092986608783489580

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Colorectal cancer model metabolic interventions and tracing.

limitations

Context-specific rerouting; it does not establish a universal protective effect of MPC inhibition.

nutrient_topic

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

plain_language

Changing use of alanine in mitochondria changed its availability to another pathway.

primary_references

Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 464–470

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Colorectal cancer model metabolic interventions and tracing. · source_derived_draft · unverified_draft

## alanine-serine-mpc-interaction Changing use of alanine in mitochondria changed its availability to another pathway. Targeting mitochondrial pyruvate transport promoted alanine oxidation, reduced deoxysphingolipid production and restored growth under serine/glycine-restricted conditions. Model: Colorectal cancer model metabolic interventions and tracing. Limitations: Context-specific rerouting; it does not establish a universal protective effect of MPC inhibition. Evidence access: Primary full text Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts.

limitations

Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine.

nutrient_topic

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

plain_language

The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting.

primary_references

Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 456–462

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. · source_derived_draft · unverified_draft

## alanine-serine-restriction-lipids The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting. Serine/glycine restriction increased alanine-derived deoxysphingolipid synthesis in the tested colorectal cancer models and constrained growth. Model: Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. Limitations: Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine. Evidence access: Primary full text Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B6-dependent glycine cleavage supplies folate one-carbon chemistry.

experimental_model

Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion.

exposure

Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L.

limitations

Whole-body kinetics do not resolve separate organs or prove severe deficiency harmless.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

This folate-linked carbon supply remained measurable despite lower blood B6.

primary_references

[b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184

tissue_or_cell_type

Human blood and whole-body measurements

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1397–1408

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. · source_derived_draft · unverified_draft

### b6-glycine-cleavage-resilience Restriction did not significantly change glycine cleavage or serine synthesis from GCS-derived one-carbon units. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This folate-linked carbon supply remained measurable despite lower blood B6. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. limitations: Whole-body kinetics do not resolve separate organs or prove severe deficiency harmless. exposure: Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L. cross_nutrient: B6-dependent glycine cleavage supplies folate one-carbon chemistry. [b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B6 and folate participate in a reversible reaction; flux direction matters.

experimental_model

Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion.

exposure

Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L.

limitations

Do not substitute the reverse serine-to-glycine direction or identify the responsible SHMT compartment from whole-body data.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

The measured direction ran faster, rather than shutting down.

primary_references

[b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184

tissue_or_cell_type

Human blood and whole-body measurements

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1410–1421

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. · source_derived_draft · unverified_draft

### b6-glycine-serine-flux-increase SHMT-mediated glycine-to-serine conversion increased 182 to 205 micromol/kg/hour during restriction, accompanied by higher plasma glycine. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured direction ran faster, rather than shutting down. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Thirteen healthy adults (seven men, six women; ages 20–39); glycine and leucine stable-isotope infusion. limitations: Do not substitute the reverse serine-to-glycine direction or identify the responsible SHMT compartment from whole-body data. exposure: Moderate dietary B6 restriction; plasma PLP55±4 to 23±1 nmol/L. cross_nutrient: B6 and folate participate in a reversible reaction; flux direction matters. [b6-lamers2009] Moderate dietary vitamin B-6 restriction raises plasma glycine and cystathionine concentrations while minimally affecting the rates of glycine turnover and glycine cleavage in healthy men and women (2009). https://pubmed.ncbi.nlm.nih.gov/19158217/ DOI: 10.3945/jn.108.099184

cross_nutrient

B6 and glycine support the porphyrin precursor pathway upstream of iron insertion.

experimental_model

Purified recombinant human ALAS2; crystallography and kinetics

limitations

Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction.

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 step starts erythroid heme synthesis.

primary_references

[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 799–809

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ALAS2; crystallography and kinetics · source_derived_draft · unverified_draft

### b6-met-alas2-ala Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step starts erythroid heme synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human ALAS2; crystallography and kinetics limitations: Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction. cross_nutrient: B6 and glycine support the porphyrin precursor pathway upstream of iron insertion. [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x

cross_nutrient

PLP (B6) and THF (folate) cooperate in one reaction.

experimental_model

Purified human SHMT1 and SHMT2; structures and solution oligomerization

limitations

Reaction is reversible; assembly assays do not establish flux in every cell.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.

primary_references

[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 602–612

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft

### b6-met-shmt1-onecarbon Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211

cross_nutrient

PLP (B6) and THF (folate) cooperate in one reaction.

experimental_model

Purified human SHMT1 and SHMT2; structures and solution oligomerization

limitations

Reaction is reversible; assembly assays do not establish flux in every cell.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.

primary_references

[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 614–624

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft

### b6-met-shmt2-onecarbon Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211

evidence_access

Primary abstract

experimental_model

Recombinant human enzyme.

limitations

Shared enzyme use does not establish clinical competition or a need to balance glycine and taurine supplements.

nutrient_topic

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

plain_language

Glycine and taurine converge on the same bile-conjugating enzyme.

primary_references

Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8034703/

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 305–311

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

## taurine-baat-glycine Glycine and taurine converge on the same bile-conjugating enzyme. The same expressed human BAAT also catalyzed glycine conjugation of cholic acid. Model: Recombinant human enzyme. Limitations: Shared enzyme use does not establish clinical competition or a need to balance glycine and taurine supplements. Evidence access: Primary abstract Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8034703/

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Ten pediatric patients; bile chemistry and genetic investigation.

limitations

Not evidence that isolated dietary taurine shortage causes the same phenotype.

nutrient_topic

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

plain_language

A broken conjugation enzyme affects both amino-acid routes.

primary_references

Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23415802/ · DOI 10.1053/j.gastro.2013.02.004

trigger_kind

machinery_impairment Imported condition classification; unverified.

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 313–319

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Ten pediatric patients; bile chemistry and genetic investigation. · source_derived_draft · unverified_draft

## taurine-baat-loss A broken conjugation enzyme affects both amino-acid routes. Patients with defective bile acid amidation lacked glycine and taurine conjugates in urine, bile and serum; four homozygous BAAT mutations were identified among eight tested patients. Model: Ten pediatric patients; bile chemistry and genetic investigation. Limitations: Not evidence that isolated dietary taurine shortage causes the same phenotype. Evidence access: Primary abstract Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23415802/ · DOI 10.1053/j.gastro.2013.02.004

evidence_access

Primary abstract

experimental_model

Human receptor expressed in Xenopus oocytes or human cells; electrophysiology.

limitations

Not a clinical sedative effect; chloride gradient and receptor composition shape cellular response.

nutrient_topic

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

plain_language

Taurine can activate a receptor named for glycine.

primary_references

Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 417–423

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human receptor expressed in Xenopus oocytes or human cells; electrophysiology. · source_derived_draft · unverified_draft

## taurine-glycine-receptor-alpha1 Taurine can activate a receptor named for glycine. Applied taurine activated recombinant human alpha1 homomeric glycine receptors in oocytes and HEK293 cells; its potency and efficacy varied with the experimental receptor response. Model: Human receptor expressed in Xenopus oocytes or human cells; electrophysiology. Limitations: Not a clinical sedative effect; chloride gradient and receptor composition shape cellular response. Evidence access: Primary abstract Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

evidence_access

Primary abstract

experimental_model

Recombinant human alpha2 receptor electrophysiology.

limitations

Avoid labeling taurine a universally weak or full agonist.

nutrient_topic

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

plain_language

The receptor subtype and cell setting change the strength of taurine signaling.

primary_references

Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 425–431

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human alpha2 receptor electrophysiology. · source_derived_draft · unverified_draft

## taurine-glycine-receptor-alpha2 The receptor subtype and cell setting change the strength of taurine signaling. Applied taurine also activated human alpha2 homomeric glycine receptors, with efficacy varying from weak to full agonism across tested conditions. Model: Recombinant human alpha2 receptor electrophysiology. Limitations: Avoid labeling taurine a universally weak or full agonist. Evidence access: Primary abstract Activation of human alpha1 and alpha2 homomeric glycine receptors by taurine and GABA. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11559772/ · DOI 10.1111/j.1469-7793.2001.t01-1-00741.x

evidence_span

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experimental_model

Radiolabeled disposition experiment

exposure

2 or 250 mg/kg intraperitoneal, with an additional 250 mg/kg oral arm

limitations

High experimental exposures and rodent species; metabolite recovery does not quantify human nutrient demand or identify every enzyme.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Rats and mice

plain_language

The two rodent species did not handle every conjugation pathway identically.

primary_references

[ceylon-p7959441] Studies on trans-cinnamaldehyde. 1. The influence of dose size and sex on its disposition in the rat and mouse. (1994). https://pubmed.ncbi.nlm.nih.gov/7959441/ DOI: 10.1016/0278-6915(94)90084-1

tissue_or_cell_type

Urine and excreta

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 233–244

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

### ceylon-cinnamoylglycine A cinnamic-acid glycine conjugate appeared in substantial amounts only in mice in the rat/mouse comparison. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two rodent species did not handle every conjugation pathway identically. organism: Rats and mice tissue_or_cell_type: Urine and excreta experimental_model: Radiolabeled disposition experiment limitations: High experimental exposures and rodent species; metabolite recovery does not quantify human nutrient demand or identify every enzyme. exposure: 2 or 250 mg/kg intraperitoneal, with an additional 250 mg/kg oral arm evidence_span: {"source_cache": "artifacts/ceylon-research/7959441.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5bab6bd0ad082e4064c601368d147bfcd87566a98ba749a37974fb1057e8c1be", "start_char": 0, "end_char": 1564, "text_sha256": "5bab6bd0ad082e4064c601368d147bfcd87566a98ba749a37974fb1057e8c1be"} [ceylon-p7959441] Studies on trans-cinnamaldehyde. 1. The influence of dose size and sex on its disposition in the rat and mouse. (1994). https://pubmed.ncbi.nlm.nih.gov/7959441/ DOI: 10.1016/0278-6915(94)90084-1

evidence_span

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experimental_model

Radiolabeled disposition experiment

exposure

2 or 250 mg/kg intraperitoneal, with an additional 250 mg/kg oral arm

limitations

High experimental exposures and rodent species; metabolite recovery does not quantify human nutrient demand or identify every enzyme.

nutrient_topic

Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. · Ceylon cinnamon / Cinnamomum verum bark preparations

organism

Rats and mice

plain_language

Much of the measured rodent dose left as hippurate, a benzoate-glycine conjugate.

primary_references

[ceylon-p7959441] Studies on trans-cinnamaldehyde. 1. The influence of dose size and sex on its disposition in the rat and mouse. (1994). https://pubmed.ncbi.nlm.nih.gov/7959441/ DOI: 10.1016/0278-6915(94)90084-1

tissue_or_cell_type

Urine and excreta

Ceylon cinnamon: metabolism, signaling and nutrient connections (2026-09-17) · lines 194–205

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

### ceylon-hippurate Hippuric acid was the major urinary metabolite after radiolabeled trans-cinnamaldehyde administration in rats and mice. Condition category: normal nutrient_topic: Ceylon cinnamon research collection; topical membership is not evidence of a direct dietary effect. plain_language: Much of the measured rodent dose left as hippurate, a benzoate-glycine conjugate. organism: Rats and mice tissue_or_cell_type: Urine and excreta experimental_model: Radiolabeled disposition experiment limitations: High experimental exposures and rodent species; metabolite recovery does not quantify human nutrient demand or identify every enzyme. exposure: 2 or 250 mg/kg intraperitoneal, with an additional 250 mg/kg oral arm evidence_span: {"source_cache": "artifacts/ceylon-research/7959441.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5bab6bd0ad082e4064c601368d147bfcd87566a98ba749a37974fb1057e8c1be", "start_char": 0, "end_char": 1564, "text_sha256": "5bab6bd0ad082e4064c601368d147bfcd87566a98ba749a37974fb1057e8c1be"} [ceylon-p7959441] Studies on trans-cinnamaldehyde. 1. The influence of dose size and sex on its disposition in the rat and mouse. (1994). https://pubmed.ncbi.nlm.nih.gov/7959441/ DOI: 10.1016/0278-6915(94)90084-1

evidence_access

Primary abstract

experimental_model

Rat liver GNMT crystallography and binding experiments.

limitations

Rat enzyme and defined ligand conditions; not a demonstrated human supplement interaction.

nutrient_topic

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

plain_language

Folate can regulate methyl-group disposal through glycine.

primary_references

5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17158459/ · DOI 10.1074/jbc.M610384200

L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 212–218

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

## methionine-gnmt-folate-structure Folate can regulate methyl-group disposal through glycine. Rat GNMT structures located two folate-binding sites between subunits; occupancy restricts the N-terminal movements needed for substrate access. Model: Rat liver GNMT crystallography and binding experiments. Limitations: Rat enzyme and defined ligand conditions; not a demonstrated human supplement interaction. Evidence access: Primary abstract 5-methyltetrahydrofolate is bound in intersubunit areas of rat liver folate-binding protein glycine N-methyltransferase. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17158459/ · DOI 10.1074/jbc.M610384200

evidence_span

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experimental_model

Human AGAT crystal structures and inactive-mutant substrate complex

exposure

Native, ornithine-bound and inactive mutant structures

limitations

Structures support an amidino-transfer mechanism; substrate availability in a person and effects of amino-acid supplementation were not measured.

nutrient_topic

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

organism

Recombinant human enzyme

plain_language

The first synthesis step joins material from arginine and glycine to make the precursor of creatine.

primary_references

[creatine-p9218780] Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. (1997). https://pubmed.ncbi.nlm.nih.gov/9218780/ DOI: 10.1093/emboj/16.12.3373

tissue_or_cell_type

Purified protein

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 177–188

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human AGAT crystal structures and inactive-mutant substrate complex · source_derived_draft · unverified_draft

### creatine-agat-reaction AGAT catalyzes transfer of an amidino group from arginine to glycine, forming guanidinoacetate and ornithine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first synthesis step joins material from arginine and glycine to make the precursor of creatine. organism: Recombinant human enzyme tissue_or_cell_type: Purified protein experimental_model: Human AGAT crystal structures and inactive-mutant substrate complex limitations: Structures support an amidino-transfer mechanism; substrate availability in a person and effects of amino-acid supplementation were not measured. exposure: Native, ornithine-bound and inactive mutant structures evidence_span: {"source_cache": "artifacts/creatine-research/9218780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b", "start_char": 0, "end_char": 1112, "text_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b"} [creatine-p9218780] Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. (1997). https://pubmed.ncbi.nlm.nih.gov/9218780/ DOI: 10.1093/emboj/16.12.3373

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": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"}

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

A second enzyme, glycine and energy complete the molecule.

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 853–864

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

### sulforaphane-gss-second-step Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second enzyme, glycine and energy complete the molecule. 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": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008

evidence_access

Primary abstract

experimental_model

Small treated human case series.

limitations

No untreated comparator; association does not quantify an ordinary food-preservative effect.

nutrient_topic

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

plain_language

Using one conjugation route can be accompanied by loss of another nutrient.

primary_references

Benzoate therapy and carnitine deficiency in non-ketotic hyperglycinemia. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8585564/ · DOI 10.1002/ajmg.1320590410

Glycine: supply, one-carbon allocation, receptors 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 · Small treated human case series. · source_derived_draft · unverified_draft

## glycine-benzoate-carnitine Using one conjugation route can be accompanied by loss of another nutrient. During sodium-benzoate treatment of five neonatal-onset nonketotic-hyperglycinemia patients, three of four tested had plasma carnitine deficiency and benzoylcarnitine was detected. Model: Small treated human case series. Limitations: No untreated comparator; association does not quantify an ordinary food-preservative effect. Evidence access: Primary abstract Benzoate therapy and carnitine deficiency in non-ketotic hyperglycinemia. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8585564/ · DOI 10.1002/ajmg.1320590410

evidence_access

Primary abstract

experimental_model

Human nonketotic-hyperglycinemia case series.

limitations

Do not infer a general glycine/carnitine supplement combination or a dosing recommendation.

nutrient_topic

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

plain_language

A measured treatment-associated nutrient deficit responded to replacement.

primary_references

Benzoate therapy and carnitine deficiency in non-ketotic hyperglycinemia. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8585564/ · DOI 10.1002/ajmg.1320590410

Glycine: supply, one-carbon allocation, receptors 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 · Human nonketotic-hyperglycinemia case series. · source_derived_draft · unverified_draft

## glycine-benzoate-carnitine-repletion A measured treatment-associated nutrient deficit responded to replacement. L-carnitine treatment normalized plasma free carnitine in the reported benzoate-treated patients; increased glycine conjugation was a tendency rather than a definitive outcome. Model: Human nonketotic-hyperglycinemia case series. Limitations: Do not infer a general glycine/carnitine supplement combination or a dosing recommendation. Evidence access: Primary abstract Benzoate therapy and carnitine deficiency in non-ketotic hyperglycinemia. · 1995 · https://pubmed.ncbi.nlm.nih.gov/8585564/ · DOI 10.1002/ajmg.1320590410

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Zebrafish supplementation experiment.

limitations

Combination rescue is recorded without claiming clinical efficacy or statistical synergy in humans.

nutrient_topic

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

plain_language

A second nutrient changed the response to the first in this model.

primary_references

Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26821380/ · DOI 10.1371/journal.pgen.1005783

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Zebrafish supplementation experiment. · source_derived_draft · unverified_draft

## glycine-fish-glycine-folate A second nutrient changed the response to the first in this model. Adding folate with glycine restored hemoglobin in the tested zebrafish Slc25a38-deficiency model. Model: Zebrafish supplementation experiment. Limitations: Combination rescue is recorded without claiming clinical efficacy or statistical synergy in humans. Evidence access: Primary full text Glycine and Folate Ameliorate Models of Congenital Sideroblastic Anemia. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26821380/ · DOI 10.1371/journal.pgen.1005783

evidence_access

Primary abstract

experimental_model

Cancer-cell nutrient and formate rescue experiment.

limitations

No extrapolation to treating cancer or supplement combinations in people.

nutrient_topic

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

plain_language

Another input changed whether supplied glycine could support growth.

primary_references

Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24813884/ · DOI 10.1016/j.celrep.2014.04.045

Glycine: supply, one-carbon allocation, receptors 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 · Cancer-cell nutrient and formate rescue experiment. · source_derived_draft · unverified_draft

## glycine-formate-serine-deprived-rescue Another input changed whether supplied glycine could support growth. Formate restored nucleotide synthesis and growth in glycine-fed cells lacking serine. Model: Cancer-cell nutrient and formate rescue experiment. Limitations: No extrapolation to treating cancer or supplement combinations in people. Evidence access: Primary abstract Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24813884/ · DOI 10.1016/j.celrep.2014.04.045

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Single human case with tissue enzyme assays, sequencing and fibroblast immunoblotting.

limitations

The authors support a likely causal genotype; a single case is not proof of a universal mechanism or a glycine-replacement response.

nutrient_topic

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

plain_language

A glycine-using translation defect can affect cellular energy systems.

primary_references

Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause mitochondrial respiratory chain dysfunction. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28594869/ · DOI 10.1371/journal.pone.0178125

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Single human case with tissue enzyme assays, sequencing and fibroblast immunoblotting. · source_derived_draft · unverified_draft

## glycine-gars-human-variants A glycine-using translation defect can affect cellular energy systems. A patient with compound GARS variants had tissue respiratory-chain deficiencies and reduced GARS/complex-IV protein in fibroblasts. Model: Single human case with tissue enzyme assays, sequencing and fibroblast immunoblotting. Limitations: The authors support a likely causal genotype; a single case is not proof of a universal mechanism or a glycine-replacement response. Evidence access: Primary full text Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause mitochondrial respiratory chain dysfunction. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28594869/ · DOI 10.1371/journal.pone.0178125

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse developmental model and formate supplementation.

limitations

Does not establish treatment of human nonketotic hyperglycinemia or prove all disease features are formate-responsive.

nutrient_topic

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

plain_language

A downstream carbon donor bypassed part of the missing pathway.

primary_references

Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25736695/ · DOI 10.1038/ncomms7388

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Mouse developmental model and formate supplementation. · source_derived_draft · unverified_draft

## glycine-gldc-formate-bypass A downstream carbon donor bypassed part of the missing pathway. Formate treatment normalized folate profiles, restored embryonic growth and prevented neural-tube defects in the tested Gldc-deficient mice. Model: Mouse developmental model and formate supplementation. Limitations: Does not establish treatment of human nonketotic hyperglycinemia or prove all disease features are formate-responsive. Evidence access: Primary full text Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25736695/ · DOI 10.1038/ncomms7388

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse gene-trap model; enzyme activity and tissue metabolites.

limitations

Inherited processing failure is distinct from insufficient dietary glycine.

nutrient_topic

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

plain_language

Excess glycine can coexist with a shortage of products made from it.

primary_references

Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25736695/ · DOI 10.1038/ncomms7388

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Mouse gene-trap model; enzyme activity and tissue metabolites. · source_derived_draft · unverified_draft

## glycine-gldc-one-carbon-loss Excess glycine can coexist with a shortage of products made from it. Reducing Gldc expression in mice suppressed glycine cleavage and depleted one-carbon-bearing folates while glycine accumulated. Model: Mouse gene-trap model; enzyme activity and tissue metabolites. Limitations: Inherited processing failure is distinct from insufficient dietary glycine. Evidence access: Primary full text Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25736695/ · DOI 10.1038/ncomms7388

evidence_access

Primary full text

experimental_model

Purified human GLYAT haplotypes, two-substrate kinetic analysis.

limitations

Reaction uses an activated acyl-CoA, not free benzoate; pathway activation and CoA release remain separate steps.

nutrient_topic

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

plain_language

Activated acyl groups can be transferred onto glycine for disposal.

primary_references

Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl-CoA. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33803916/ · DOI 10.3390/ijms22063129

Glycine: supply, one-carbon allocation, receptors 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 · Purified human GLYAT haplotypes, two-substrate kinetic analysis. · source_derived_draft · unverified_draft

## glycine-glyat-benzoyl Activated acyl groups can be transferred onto glycine for disposal. Recombinant human GLYAT variants conjugated glycine to benzoyl-CoA in kinetic assays, forming the glycine-conjugation product hippurate. Model: Purified human GLYAT haplotypes, two-substrate kinetic analysis. Limitations: Reaction uses an activated acyl-CoA, not free benzoate; pathway activation and CoA release remain separate steps. Evidence access: Primary full text Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl-CoA. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33803916/ · DOI 10.3390/ijms22063129

evidence_access

Primary full text

experimental_model

Recombinant enzyme validation alongside docking.

limitations

The causal evidence recorded here is the enzyme assay, not the docking prediction; whole-body contribution is unresolved.

nutrient_topic

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

plain_language

Glycine conjugation can intersect with leucine-breakdown metabolites.

primary_references

The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36817957/ · DOI 10.1016/j.csbj.2023.01.041

Glycine: supply, one-carbon allocation, receptors 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 · Recombinant enzyme validation alongside docking. · source_derived_draft · unverified_draft

## glycine-glyat-isovaleryl Glycine conjugation can intersect with leucine-breakdown metabolites. Purified GLYAT formed N-isovalerylglycine from isovaleryl-CoA and glycine in vitro, with lower affinity than for its preferred substrate. Model: Recombinant enzyme validation alongside docking. Limitations: The causal evidence recorded here is the enzyme assay, not the docking prediction; whole-body contribution is unresolved. Evidence access: Primary full text The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36817957/ · DOI 10.1016/j.csbj.2023.01.041

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Recombinant haplotype kinetics; not a patient treatment trial.

limitations

Potential clinical consequences remain untested; do not equate genotype with a known glycine-deficiency syndrome.

nutrient_topic

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

plain_language

Tighter apparent binding did not mean faster detoxification.

primary_references

Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl-CoA. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33803916/ · DOI 10.3390/ijms22063129

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Recombinant haplotype kinetics; not a patient treatment trial. · source_derived_draft · unverified_draft

## glycine-glyat-variant Tighter apparent binding did not mean faster detoxification. The human GLYAT N156S/R199C variant had turnover about 9.8% of the common N156S reference haplotype in vitro despite greater apparent benzoyl-CoA affinity. Model: Recombinant haplotype kinetics; not a patient treatment trial. Limitations: Potential clinical consequences remain untested; do not equate genotype with a known glycine-deficiency syndrome. Evidence access: Primary full text Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl-CoA. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33803916/ · DOI 10.3390/ijms22063129

evidence_access

Primary full text

experimental_model

Purified enzyme assays.

limitations

Does not establish which enzyme dominates in a patient.

nutrient_topic

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

plain_language

A related enzyme provides another possible route to the same product.

primary_references

The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36817957/ · DOI 10.1016/j.csbj.2023.01.041

Glycine: supply, one-carbon allocation, receptors 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 · Purified enzyme assays. · source_derived_draft · unverified_draft

## glycine-glyatl1-isovaleryl A related enzyme provides another possible route to the same product. Purified GLYATL1 also supported N-isovalerylglycine formation in vitro, less favorably than its preferred substrate reaction. Model: Purified enzyme assays. Limitations: Does not establish which enzyme dominates in a patient. Evidence access: Primary full text The glycine N-acyltransferases, GLYAT and GLYATL1, contribute to the detoxification of isovaleryl-CoA - an in-silico and in vitro validation. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36817957/ · DOI 10.1016/j.csbj.2023.01.041

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cancer-cell comparison under culture glycine withdrawal.

limitations

A local experimental shortage, not a universal human dietary deficiency threshold.

nutrient_topic

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

plain_language

Some cells depend more on imported glycine than others.

primary_references

Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Human cancer-cell comparison under culture glycine withdrawal. · source_derived_draft · unverified_draft

## glycine-glycine-withdrawal Some cells depend more on imported glycine than others. Removing extracellular glycine alone slowed LOX IMVI proliferation but did not impair A498 cells in the same study. Model: Human cancer-cell comparison under culture glycine withdrawal. Limitations: A local experimental shortage, not a universal human dietary deficiency threshold. Evidence access: Primary full text Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording.

limitations

Modeling implicated impaired gating rather than simply loss of ligand binding; not dietary glycine deficiency.

nutrient_topic

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

plain_language

The receptor can respond poorly even when its ligand is supplied.

primary_references

Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9490812/ · DOI 10.1111/j.1469-7793.1998.025bu.x

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording. · source_derived_draft · unverified_draft

## glycine-glyr-variant The receptor can respond poorly even when its ligand is supplied. Human alpha1(K276E)/beta receptors expressed in Xenopus oocytes were about 29-fold less glycine-sensitive than wild type and had shorter channel openings. Model: Human disease-associated receptor constructs in frog oocytes; concentration-response and single-channel recording. Limitations: Modeling implicated impaired gating rather than simply loss of ligand binding; not dietary glycine deficiency. Evidence access: Primary abstract Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9490812/ · DOI 10.1111/j.1469-7793.1998.025bu.x

evidence_access

Primary full text

experimental_model

Human GlyT1/GlyT2 voltage-clamp measurements and kinetic models.

limitations

Binding-order models are interpretations constrained by currents, not direct structures of every transport state.

nutrient_topic

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

plain_language

Raising one intracellular ion did not simply switch these transporters off.

primary_references

A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

Glycine: supply, one-carbon allocation, receptors 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 GlyT1/GlyT2 voltage-clamp measurements and kinetic models. · source_derived_draft · unverified_draft

## glycine-glyt-ion-cooperativity Raising one intracellular ion did not simply switch these transporters off. GlyT1 and GlyT2 maintained forward transport under the tested elevated intracellular sodium or chloride conditions, consistent with cooperative ion/substrate binding. Model: Human GlyT1/GlyT2 voltage-clamp measurements and kinetic models. Limitations: Binding-order models are interpretations constrained by currents, not direct structures of every transport state. Evidence access: Primary full text A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31270129/ · DOI 10.1085/jgp.201912318

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human family sequencing and biochemical phenotyping.

limitations

Small rare-disease series; CSF abnormality is not inferred in untested relatives or healthy people.

nutrient_topic

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

plain_language

A normal blood result can miss an abnormal brain-fluid pool.

primary_references

Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27773429/ · DOI 10.1016/j.ajhg.2016.09.004

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 family sequencing and biochemical phenotyping. · source_derived_draft · unverified_draft

## glycine-glyt1-human-loss A normal blood result can miss an abnormal brain-fluid pool. Four affected individuals from two families had truncating SLC6A9 variants; two tested individuals had mildly elevated CSF glycine with normal serum glycine. Model: Human family sequencing and biochemical phenotyping. Limitations: Small rare-disease series; CSF abnormality is not inferred in untested relatives or healthy people. Evidence access: Primary abstract Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27773429/ · DOI 10.1016/j.ajhg.2016.09.004

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse knockout; neuronal electrophysiology and postnatal neuromotor phenotype.

limitations

Transporter deletion is not dietary glycine deficiency.

nutrient_topic

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

plain_language

Loss of replenishment machinery weakens inhibitory transmitter output.

primary_references

Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14622583/ · DOI 10.1016/s0896-6273(03)00673-1

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Mouse knockout; neuronal electrophysiology and postnatal neuromotor phenotype. · source_derived_draft · unverified_draft

## glycine-glyt2-loss Loss of replenishment machinery weakens inhibitory transmitter output. Deleting mouse Slc6a5 reduced glycinergic miniature inhibitory-current amplitudes in hypoglossal motoneurons and dissociated spinal neurons. Model: Mouse knockout; neuronal electrophysiology and postnatal neuromotor phenotype. Limitations: Transporter deletion is not dietary glycine deficiency. Evidence access: Primary abstract Deletion of the mouse glycine transporter 2 results in a hyperekplexia phenotype and postnatal lethality. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14622583/ · DOI 10.1016/s0896-6273(03)00673-1

evidence_access

Primary full text

experimental_model

Recombinant expression and cAMP biosensors.

limitations

Direction of cAMP regulation is cell-context dependent; do not infer universal cAMP lowering.

nutrient_topic

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

plain_language

A receptor connects glycine to an intracellular messenger.

primary_references

Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

Glycine: supply, one-carbon allocation, receptors 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 · Recombinant expression and cAMP biosensors. · source_derived_draft · unverified_draft

## glycine-gpr158-camp A receptor connects glycine to an intracellular messenger. Added glycine reduced cAMP in GPR158-expressing U87 and HEK293 assays; coexpression of RGS7/G-beta5 strengthened the response. Model: Recombinant expression and cAMP biosensors. Limitations: Direction of cAMP regulation is cell-context dependent; do not infer universal cAMP lowering. Evidence access: Primary full text Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

evidence_access

Primary full text

experimental_model

Mouse acute slices, intrinsic-current measurements and knockout comparison.

limitations

High bath exposure; absence of effect in layer V reinforces cell-type specificity.

nutrient_topic

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

plain_language

This receptor can make selected neurons more excitable.

primary_references

Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

Glycine: supply, one-carbon allocation, receptors 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 · Mouse acute slices, intrinsic-current measurements and knockout comparison. · source_derived_draft · unverified_draft

## glycine-gpr158-cortex This receptor can make selected neurons more excitable. Bath glycine at 1 mM increased layer-II/III prefrontal neuronal excitability in control mice but not Gpr158-knockout mice under synaptic receptor blockade. Model: Mouse acute slices, intrinsic-current measurements and knockout comparison. Limitations: High bath exposure; absence of effect in layer V reinforces cell-type specificity. Evidence access: Primary full text Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

evidence_access

Primary full text

experimental_model

Mouse slice pharmacological inhibition and phosphorylation assays.

limitations

Associated phosphorylation and inhibitor effects do not establish every kinase-substrate step; cholinergic interneurons did not share the firing response.

nutrient_topic

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

plain_language

The channel response depends on intracellular signaling steps.

primary_references

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w

Glycine: supply, one-carbon allocation, receptors 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 · Mouse slice pharmacological inhibition and phosphorylation assays. · source_derived_draft · unverified_draft

## glycine-gpr158-kinase-dependence The channel response depends on intracellular signaling steps. Blocking PKA or ERK signaling suppressed the glycine-associated increase in medium-spiny-neuron excitability; ERK and Kv7.2 serine phosphorylation increased in the study. Model: Mouse slice pharmacological inhibition and phosphorylation assays. Limitations: Associated phosphorylation and inhibitor effects do not establish every kinase-substrate step; cholinergic interneurons did not share the firing response. Evidence access: Primary full text Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38884814/ · DOI 10.1007/s00018-024-05260-w

evidence_access

Primary full text

experimental_model

Membrane ligand competition and cell signaling.

limitations

Shared binding is not proof of supplement synergy or the same neuronal response.

nutrient_topic

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

plain_language

Another nutrient-related molecule reaches the same receptor with a different response.

primary_references

Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

Glycine: supply, one-carbon allocation, receptors 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 · Membrane ligand competition and cell signaling. · source_derived_draft · unverified_draft

## glycine-gpr158-taurine Another nutrient-related molecule reaches the same receptor with a different response. Taurine competed for GPR158 glycine binding and produced weaker cAMP suppression than glycine in the recombinant assays. Model: Membrane ligand competition and cell signaling. Limitations: Shared binding is not proof of supplement synergy or the same neuronal response. Evidence access: Primary full text Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36996198/ · DOI 10.1126/science.add7150

evidence_access

Primary abstract

experimental_model

Rat immune-cell ion substitution and antagonist experiments.

limitations

Pharmacology does not uniquely identify a receptor-subunit combination; high-dose strychnine behaved differently.

nutrient_topic

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

plain_language

The ionic environment was required for the observed response.

primary_references

Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

Glycine: supply, one-carbon allocation, receptors 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 · Rat immune-cell ion substitution and antagonist experiments. · source_derived_draft · unverified_draft

## glycine-kupffer-chloride-dependence The ionic environment was required for the observed response. Chloride-free buffer abolished the reported glycine effect, and 1 micromolar strychnine reversed it; glycine hyperpolarized the tested Kupffer cells. Model: Rat immune-cell ion substitution and antagonist experiments. Limitations: Pharmacology does not uniquely identify a receptor-subunit combination; high-dose strychnine behaved differently. Evidence access: Primary abstract Kupffer cells contain a glycine-gated chloride channel. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9227496/ · DOI 10.1152/ajpgi.1997.272.6.G1581

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human family genotype/functional analysis.

limitations

Modifier evidence is not proof of ordinary dietary competition between glycine and proline.

nutrient_topic

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

plain_language

A second transporter can change the effect of the first defect.

primary_references

Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. · 2008 · https://pubmed.ncbi.nlm.nih.gov/19033659/ · DOI 10.1172/JCI36625

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Human family genotype/functional analysis. · source_derived_draft · unverified_draft

## glycine-renal-modifier A second transporter can change the effect of the first defect. SLC6A20 mutations accompanied iminoglycinuria when combined with SLC36A2 variants retaining residual transport. Model: Human family genotype/functional analysis. Limitations: Modifier evidence is not proof of ordinary dietary competition between glycine and proline. Evidence access: Primary abstract Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. · 2008 · https://pubmed.ncbi.nlm.nih.gov/19033659/ · DOI 10.1172/JCI36625

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human family genetics with functional transporter testing.

limitations

This is renal handling; urinary loss alone does not establish systemic nutritional deficiency.

nutrient_topic

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

plain_language

The kidney can lose glycine because its recovery transporter is faulty.

primary_references

Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. · 2008 · https://pubmed.ncbi.nlm.nih.gov/19033659/ · DOI 10.1172/JCI36625

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Human family genetics with functional transporter testing. · source_derived_draft · unverified_draft

## glycine-renal-pat2 The kidney can lose glycine because its recovery transporter is faulty. Inheritance and functional studies in seven families implicated nonfunctional SLC36A2 alleles in urinary glycine and imino-acid loss; two defective alleles tracked iminoglycinuria and one tracked hyperglycinuria. Model: Human family genetics with functional transporter testing. Limitations: This is renal handling; urinary loss alone does not establish systemic nutritional deficiency. Evidence access: Primary abstract Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters. · 2008 · https://pubmed.ncbi.nlm.nih.gov/19033659/ · DOI 10.1172/JCI36625

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human leukemia cells, knockout and metabolite-rescue experiment.

limitations

Culture rescue is not a nutritional recommendation; this growth endpoint differs from zebrafish hemoglobin.

nutrient_topic

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

plain_language

Restoring a downstream one-carbon source worked where adding an amino acid did not.

primary_references

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Human leukemia cells, knockout and metabolite-rescue experiment. · source_derived_draft · unverified_draft

## glycine-s38-formate-rescue Restoring a downstream one-carbon source worked where adding an amino acid did not. Formate at 1 mM rescued the low-B6 proliferation defect of SLC25A38-null K562 cells, while glycine, serine and folate did not under the tested conditions. Model: Human leukemia cells, knockout and metabolite-rescue experiment. Limitations: Culture rescue is not a nutritional recommendation; this growth endpoint differs from zebrafish hemoglobin. Evidence access: Primary full text SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human K562 knockout, isotope tracing and controlled B6 culture conditions.

limitations

Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38.

nutrient_topic

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

plain_language

A mitochondrial cofactor problem reduced the cell's ability to make glycine.

primary_references

SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Human K562 knockout, isotope tracing and controlled B6 culture conditions. · source_derived_draft · unverified_draft

## glycine-s38-glycine-synthesis A mitochondrial cofactor problem reduced the cell's ability to make glycine. SLC25A38 loss reduced deuterated-serine incorporation into glycine and glycine-derived glutathione under low-B6 conditions. Model: Human K562 knockout, isotope tracing and controlled B6 culture conditions. Limitations: Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38. Evidence access: Primary full text SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human melanoma cultures with shRNA and nutrient withdrawal/rescue.

limitations

A combined manipulation; not proof that ordinary dietary glycine alone controls a tumor.

nutrient_topic

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

plain_language

Removing both synthesis and external supply exposed a glycine dependency.

primary_references

Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595

trigger_kind

machinery_impairment Imported condition classification; unverified.

Glycine: supply, one-carbon allocation, receptors 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 · Human melanoma cultures with shRNA and nutrient withdrawal/rescue. · source_derived_draft · unverified_draft

## glycine-shmt2-glycine-dependence Removing both synthesis and external supply exposed a glycine dependency. SHMT2 silencing combined with removal of extracellular glycine halted LOX IMVI proliferation; adding glycine restored growth whereas formate did not. Model: Human melanoma cultures with shRNA and nutrient withdrawal/rescue. Limitations: A combined manipulation; not proof that ordinary dietary glycine alone controls a tumor. Evidence access: Primary full text Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595

evidence_access

Primary abstract

experimental_model

Rat brain injection and antagonist experiments.

limitations

Antagonist evidence supports pathway involvement; does not show all sleep effects use this route.

nutrient_topic

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

plain_language

The tested sleep-related response used a different receptor route from the inhibitory glycine channel.

primary_references

The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533534/ · DOI 10.1038/npp.2014.326

Glycine: supply, one-carbon allocation, receptors 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 brain injection and antagonist experiments. · source_derived_draft · unverified_draft

## glycine-sleep-nmda-route The tested sleep-related response used a different receptor route from the inhibitory glycine channel. NMDA-receptor antagonists blocked glycine-associated cutaneous blood-flow responses in the rat experiments, whereas strychnine did not. Model: Rat brain injection and antagonist experiments. Limitations: Antagonist evidence supports pathway involvement; does not show all sleep effects use this route. Evidence access: Primary abstract The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533534/ · DOI 10.1038/npp.2014.326

evidence_access

Primary abstract

experimental_model

Established reaction described in a primary human GARS disease study.

limitations

Background enzyme chemistry is distinguished from the patient measurements; separate cytosolic/mitochondrial isoform kinetics were not measured here.

nutrient_topic

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

plain_language

A charging enzyme attaches glycine to the RNA adapter used to build protein.

primary_references

Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause mitochondrial respiratory chain dysfunction. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28594869/ · DOI 10.1371/journal.pone.0178125

Glycine: supply, one-carbon allocation, receptors 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 · Established reaction described in a primary human GARS disease study. · source_derived_draft · unverified_draft

## glycine-trna-charging A charging enzyme attaches glycine to the RNA adapter used to build protein. GARS1 catalyzes glycyl-tRNA formation for glycine incorporation into cytosolic and mitochondrial proteins. Model: Established reaction described in a primary human GARS disease study. Limitations: Background enzyme chemistry is distinguished from the patient measurements; separate cytosolic/mitochondrial isoform kinetics were not measured here. Evidence access: Primary abstract Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause mitochondrial respiratory chain dysfunction. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28594869/ · DOI 10.1371/journal.pone.0178125

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

B2-dependent mitochondrial function supports glycine carbon entry into folate-related one-carbon supply.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}]

experimental_model

Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays.

exposure

Slc25a32-null mitochondria supplied [1,2-13C2]-glycine.

limitations

Long isolated-mitochondrial assay; this is glycine-derived flux, not total cellular formate synthesis.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Mus musculus

plain_language

The same genetic defect sharply reduced one-carbon output from glycine.

primary_references

[peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0

tissue_or_cell_type

Embryo mitochondria, 24-hour isotope incubation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 888–900

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. · source_derived_draft · unverified_draft

### b2-met-mouse-null-glycine-formate Isolated Slc25a32-null embryo mitochondria produced about 10.6% of control labeled formate from [13C2]-glycine over 24 hours. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same genetic defect sharply reduced one-carbon output from glycine. organism: Mus musculus tissue_or_cell_type: Embryo mitochondria, 24-hour isotope incubation experimental_model: Slc25a32-null embryos and missense knock-in mice, isolated mitochondria and skeletal-muscle enzyme assays. limitations: Long isolated-mitochondrial assay; this is glycine-derived flux, not total cellular formate synthesis. exposure: Slc25a32-null mitochondria supplied [1,2-13C2]-glycine. cross_nutrient: B2-dependent mitochondrial function supports glycine carbon entry into folate-related one-carbon supply. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC11072207", "locator": "HTML article p", "paragraph_index": 43, "char_start": 0, "char_end": 1215, "evidence_access": "full-text"}] [peng-2022-slc25a32] Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism (2022). https://pubmed.ncbi.nlm.nih.gov/35727412/ DOI: 10.1007/s00018-022-04404-0

evidence_access

Primary full text

experimental_model

Human/mouse metabolomics study; established conjugation route described in primary full text.

limitations

This is not a purified conjugating-enzyme kinetic experiment and does not show clinically meaningful glutamine or glycine depletion.

nutrient_topic

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

plain_language

Host amino acids help turn a bacterial product into circulating metabolites.

primary_references

A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 358–364

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human/mouse metabolomics study; established conjugation route described in primary full text. · source_derived_draft · unverified_draft

## l-phenylalanine-host-conjugation Host amino acids help turn a bacterial product into circulating metabolites. Host conjugation of microbially derived phenylacetate with glutamine produces PAGln, the predominant human conjugate in the study; glycine conjugation produces PAGly, predominant in mice. Model: Human/mouse metabolomics study; established conjugation route described in primary full text. Limitations: This is not a purified conjugating-enzyme kinetic experiment and does not show clinically meaningful glutamine or glycine depletion. Evidence access: Primary full text A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32142679/ · DOI 10.1016/j.cell.2020.02.016

evidence_access

Primary abstract

experimental_model

Mouse macrophage metabolic manipulation and LPS stimulation.

limitations

IL-1beta transcription and inflammasome-mediated processing are different endpoints.

nutrient_topic

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

plain_language

An antioxidant-building pathway can support inflammatory gene expression.

primary_references

Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 230–236

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophage metabolic manipulation and LPS stimulation. · source_derived_draft · unverified_draft

## l-serine-macrophage-gsh An antioxidant-building pathway can support inflammatory gene expression. Serine-derived glycine supported glutathione synthesis required for optimal LPS-induced IL-1beta mRNA expression; inflammasome activation was not the affected step. Model: Mouse macrophage metabolic manipulation and LPS stimulation. Limitations: IL-1beta transcription and inflammasome-mediated processing are different endpoints. Evidence access: Primary abstract Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Five-patient treatment follow-up in a rare inherited disorder.

limitations

This is not evidence that ordinary low dietary intake causes the same syndrome.

nutrient_topic

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

plain_language

An internal synthesis defect can create a clinically important shortage.

primary_references

Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 86–92

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Five-patient treatment follow-up in a rare inherited disorder. · source_derived_draft · unverified_draft

## l-serine-phgdh-deficiency An internal synthesis defect can create a clinically important shortage. Patients with inherited PHGDH deficiency had low plasma and cerebrospinal-fluid serine, variably low glycine, microcephaly, seizures and severe developmental impairment. Model: Five-patient treatment follow-up in a rare inherited disorder. Limitations: This is not evidence that ordinary low dietary intake causes the same syndrome. Evidence access: Primary abstract Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Uncontrolled follow-up using different serine/glycine treatment regimens.

limitations

Small heterogeneous case series; no general supplement dose or guaranteed developmental rescue follows.

nutrient_topic

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

plain_language

Restoring supply can help some outcomes without reversing every consequence.

primary_references

Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 94–100

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Uncontrolled follow-up using different serine/glycine treatment regimens. · source_derived_draft · unverified_draft

## l-serine-phgdh-treatment Restoring supply can help some outcomes without reversing every consequence. Amino-acid therapy over 3–7.5 years reduced seizure frequency in all five reported patients, with two becoming seizure-free; developmental progress was reported in only one early-treated patient. Model: Uncontrolled follow-up using different serine/glycine treatment regimens. Limitations: Small heterogeneous case series; no general supplement dose or guaranteed developmental rescue follows. Evidence access: Primary abstract Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Two siblings; reported regimens included serine 500 mg/kg/day and glycine 200 mg/kg/day.

limitations

Case comparison is not randomized proof, a universal rescue, or a dosing recommendation.

nutrient_topic

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

plain_language

Timing may matter when early development depends on local amino-acid supply.

primary_references

Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17436247/ · DOI 10.1086/517888

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 110–116

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two siblings; reported regimens included serine 500 mg/kg/day and glycine 200 mg/kg/day. · source_derived_draft · unverified_draft

## l-serine-psat-early-treatment Timing may matter when early development depends on local amino-acid supply. Two siblings received serine plus glycine at different ages: the index child treated from 11 weeks died at seven months, whereas the sibling treated from birth had a normal reported outcome at age three. Model: Two siblings; reported regimens included serine 500 mg/kg/day and glycine 200 mg/kg/day. Limitations: Case comparison is not randomized proof, a universal rescue, or a dosing recommendation. Evidence access: Primary abstract Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17436247/ · DOI 10.1086/517888

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human cell single and double knockout comparisons.

limitations

Related transporters provide redundancy; this is not a demonstrated dietary serine deficiency.

nutrient_topic

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

plain_language

Transport capacity can limit another amino acid and nucleotide production.

primary_references

SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 150–156

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell single and double knockout comparisons. · source_derived_draft · unverified_draft

## l-serine-sfxn1-loss Transport capacity can limit another amino acid and nucleotide production. SFXN1-null human cells had impaired glycine and purine synthesis; loss of both SFXN1 and SFXN3 caused stronger defects, including dependence on exogenous glycine. Model: Human cell single and double knockout comparisons. Limitations: Related transporters provide redundancy; this is not a demonstrated dietary serine deficiency. Evidence access: Primary abstract SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528

evidence_access

Primary abstract

experimental_model

Primary study of activated T cells with in-vivo pathogen-driven expansion experiments in mice.

limitations

Species and activation context limit translation to human supplementation. Correction record: PubMed indexes a published erratum, PMID 28178570 / DOI 10.1016/j.cmet.2017.01.014. The notice body was not accessible during this curation, so its specific scope and impact remain unverified. Do not treat the original study as having received comprehensive integrity clearance. https://pubmed.ncbi.nlm.nih.gov/28178570/

nutrient_topic

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

plain_language

Fuel availability alone does not meet every requirement for immune-cell division.

primary_references

Serine Is an Essential Metabolite for Effector T Cell Expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28111214/ · DOI 10.1016/j.cmet.2016.12.011

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 214–220

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary study of activated T cells with in-vivo pathogen-driven expansion experiments in mice. · source_derived_draft · unverified_draft

## l-serine-tcell-expansion Fuel availability alone does not meet every requirement for immune-cell division. Extracellular serine supported optimal activated T-cell expansion by providing glycine and one-carbon units for nucleotide biosynthesis; adequate glucose alone did not substitute. Model: Primary study of activated T cells with in-vivo pathogen-driven expansion experiments in mice. Limitations: Species and activation context limit translation to human supplementation. Correction record: PubMed indexes a published erratum, PMID 28178570 / DOI 10.1016/j.cmet.2017.01.014. The notice body was not accessible during this curation, so its specific scope and impact remain unverified. Do not treat the original study as having received comprehensive integrity clearance. https://pubmed.ncbi.nlm.nih.gov/28178570/ Evidence access: Primary abstract Serine Is an Essential Metabolite for Effector T Cell Expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28111214/ · DOI 10.1016/j.cmet.2016.12.011

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Engineered mouse PTEN model; transcriptional, microdialysis and electrophysiological observations.

limitations

Multiple consequences of PTEN mutation remain possible; the model is not ordinary dietary deficiency. Correction record: Author correction PMID 39242973 / DOI 10.1038/s44321-024-00125-y corrects the human embryonic stem-cell neuron protocol IRB approval number to KH2017-109 from KA2018-61 and KH2020-55. It does not report a change to experimental results. https://link.springer.com/article/10.1038/s44321-024-00125-y

nutrient_topic

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

plain_language

Transporter regulation can alter the extracellular supply of two amino acids together.

primary_references

SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33428810/ · DOI 10.15252/emmm.202012632

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 214–220

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Engineered mouse PTEN model; transcriptional, microdialysis and electrophysiological observations. · source_derived_draft · unverified_draft

## l-proline-brain-transporter-increase Transporter regulation can alter the extracellular supply of two amino acids together. Mice carrying C-terminally truncated PTEN showed increased Slc6a20a expression, lower extracellular brain proline and glycine, and reduced NMDAR currents. Model: Engineered mouse PTEN model; transcriptional, microdialysis and electrophysiological observations. Limitations: Multiple consequences of PTEN mutation remain possible; the model is not ordinary dietary deficiency. Correction record: Author correction PMID 39242973 / DOI 10.1038/s44321-024-00125-y corrects the human embryonic stem-cell neuron protocol IRB approval number to KH2017-109 from KA2018-61 and KH2020-55. It does not report a change to experimental results. https://link.springer.com/article/10.1038/s44321-024-00125-y Evidence access: Primary full text SLC6A20 transporter: a novel regulator of brain glycine homeostasis and NMDAR function. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33428810/ · DOI 10.15252/emmm.202012632

evidence_access

Primary abstract

experimental_model

Anaerobic C. difficile culture in limiting medium; selenite supplementation and radiolabeled selenium protein analysis.

limitations

This bacterial growth mechanism does not establish that dietary selenium causes or prevents infection.

nutrient_topic

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

plain_language

Selenium also supports some microbial amino-acid fermentation pathways.

primary_references

Analysis of proline reduction in the nosocomial pathogen Clostridium difficile. · 2006 · https://pubmed.ncbi.nlm.nih.gov/17041035/ · DOI 10.1128/JB.01370-06

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 414–420

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Anaerobic C. difficile culture in limiting medium; selenite supplementation and radiolabeled selenium protein analysis. · source_derived_draft · unverified_draft

## l-proline-microbial-selenium Selenium also supports some microbial amino-acid fermentation pathways. Selenium supplementation was required for the increased bacterial growth yield seen with the tested Stickland amino-acid pairs; proline-related acceptors induced selenoenzyme expression. Model: Anaerobic C. difficile culture in limiting medium; selenite supplementation and radiolabeled selenium protein analysis. Limitations: This bacterial growth mechanism does not establish that dietary selenium causes or prevents infection. Evidence access: Primary abstract Analysis of proline reduction in the nosocomial pathogen Clostridium difficile. · 2006 · https://pubmed.ncbi.nlm.nih.gov/17041035/ · DOI 10.1128/JB.01370-06

evidence_access

Primary abstract

experimental_model

Receptors expressed in Xenopus oocytes and HEK293 cells; isotonic extracellular solutions.

limitations

Millimolar experimental kinetics are not physiological brain concentrations.

nutrient_topic

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

plain_language

A receptor channel can also provide an entry route.

primary_references

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

Spermidine: biosynthesis, hypusination, transport and cross-nutrient mechanisms (2026-09-19) · lines 446–452

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Receptors expressed in Xenopus oocytes and HEK293 cells; isotonic extracellular solutions. · source_derived_draft · unverified_draft

## spermidine-nmda-entry A receptor channel can also provide an entry route. Spermidine permeated activated GluN1/GluN2A and GluN1/GluN2B channels; reported Km values were 2.2 and 2.7 mM. Model: Receptors expressed in Xenopus oocytes and HEK293 cells; isotonic extracellular solutions. Limitations: Millimolar experimental kinetics are not physiological brain concentrations. Evidence access: Primary abstract Spermidine and Ca(2+), but not Na(+), can permeate NMDA receptors consisting of GluN1 and GluN2A or GluN2B in the presence of Mg(2+). · 2015 · https://pubmed.ncbi.nlm.nih.gov/26086092/ · DOI 10.1016/j.bbrc.2015.06.081

evidence_span

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experimental_model

In-vivo striatal microdialysis with receptor antagonists

exposure

Local brain theanine administration; glycine and AMPA antagonists

limitations

Direct brain dosing bypasses oral absorption and blood-brain-barrier transport. Antagonist sensitivity identifies pathway involvement, not necessarily direct theanine binding.

nutrient_topic

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

organism

Conscious rats

plain_language

A measured local transmitter response is distinct from the effect of drinking tea.

primary_references

[theanine-p18196445] Theanine, gamma-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats. (2009). https://pubmed.ncbi.nlm.nih.gov/18196445/ DOI: 10.1007/s00726-007-0020-7

tissue_or_cell_type

Striatal extracellular neurotransmitters

L-Theanine: metabolism, neural signaling, nutrient connections and human outcomes (2026-09-17) · lines 367–378

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In-vivo striatal microdialysis with receptor antagonists · source_derived_draft · unverified_draft

### theanine-striatal-glycine Local striatal theanine administration increased extracellular glycine. Condition category: normal nutrient_topic: L-Theanine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A measured local transmitter response is distinct from the effect of drinking tea. organism: Conscious rats tissue_or_cell_type: Striatal extracellular neurotransmitters experimental_model: In-vivo striatal microdialysis with receptor antagonists limitations: Direct brain dosing bypasses oral absorption and blood-brain-barrier transport. Antagonist sensitivity identifies pathway involvement, not necessarily direct theanine binding. exposure: Local brain theanine administration; glycine and AMPA antagonists evidence_span: {"source_cache": "artifacts/theanine-research/18196445.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59fdaf94d59c2f4b2981c29cd2981c043351aae1299a59a19e29979076957839", "start_char": 0, "end_char": 1118, "text_sha256": "59fdaf94d59c2f4b2981c29cd2981c043351aae1299a59a19e29979076957839"} [theanine-p18196445] Theanine, gamma-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the brain striatum interstitium in conscious rats. (2009). https://pubmed.ncbi.nlm.nih.gov/18196445/ DOI: 10.1007/s00726-007-0020-7

evidence_access

Primary abstract

experimental_model

Comparative human and mouse gene characterization.

limitations

This does not exclude all possible promiscuous enzyme activity; it rejects treating canonical human GLY1 as an established active enzyme.

nutrient_topic

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

plain_language

A second proposed glycine-producing route also differs across species.

primary_references

Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15757516/ · DOI 10.1186/1471-2164-6-32

L-Threonine: translation, intestinal barrier, metabolism 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 · Comparative human and mouse gene characterization. · source_derived_draft · unverified_draft

## l-threonine-human-aldolase-boundary A second proposed glycine-producing route also differs across species. Human GLY1 contained frameshifting deletions and a premature stop codon; its mRNA was not detected, unlike the transcribed mouse homolog. Model: Comparative human and mouse gene characterization. Limitations: This does not exclude all possible promiscuous enzyme activity; it rejects treating canonical human GLY1 as an established active enzyme. Evidence access: Primary abstract Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15757516/ · DOI 10.1186/1471-2164-6-32

evidence_access

Primary abstract

experimental_model

Human cDNA/genomic analysis; exon-6 splice-site loss in all 23 genotyped individuals.

limitations

Do not transfer intact mouse Tdh-dependent glycine and acetyl-CoA synthesis to humans.

nutrient_topic

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

plain_language

An expressed gene is not necessarily a functioning metabolic route.

primary_references

The human L-threonine 3-dehydrogenase gene is an expressed pseudogene. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12361482/ · DOI 10.1186/1471-2156-3-18

L-Threonine: translation, intestinal barrier, metabolism 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 · Human cDNA/genomic analysis; exon-6 splice-site loss in all 23 genotyped individuals. · source_derived_draft · unverified_draft

## l-threonine-human-tdh-boundary An expressed gene is not necessarily a functioning metabolic route. Human TDH transcripts encode truncated proteins because of splice-site disruption and a premature stop codon; the gene was classified as an expressed pseudogene. Model: Human cDNA/genomic analysis; exon-6 splice-site loss in all 23 genotyped individuals. Limitations: Do not transfer intact mouse Tdh-dependent glycine and acetyl-CoA synthesis to humans. Evidence access: Primary abstract The human L-threonine 3-dehydrogenase gene is an expressed pseudogene. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12361482/ · DOI 10.1186/1471-2156-3-18

evidence_access

Primary abstract

experimental_model

Mouse embryonic stem-cell metabolism and amino-acid withdrawal experiments.

limitations

Canonical human TDH is nonfunctional; this route is explicitly mouse-specific.

nutrient_topic

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

plain_language

A specialized mouse cell uses threonine as both carbon and one-carbon support.

primary_references

Dependence of mouse embryonic stem cells on threonine catabolism. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19589965/ · DOI 10.1126/science.1173288

L-Threonine: translation, intestinal barrier, metabolism 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 embryonic stem-cell metabolism and amino-acid withdrawal experiments. · source_derived_draft · unverified_draft

## l-threonine-mouse-tdh-flux A specialized mouse cell uses threonine as both carbon and one-carbon support. Mouse embryonic stem cells expressed abundant Tdh and used mitochondrial threonine catabolism to support glycine and acetyl-CoA generation. Model: Mouse embryonic stem-cell metabolism and amino-acid withdrawal experiments. Limitations: Canonical human TDH is nonfunctional; this route is explicitly mouse-specific. Evidence access: Primary abstract Dependence of mouse embryonic stem cells on threonine catabolism. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19589965/ · DOI 10.1126/science.1173288

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse stem-cell isotope tracing and culture-medium withdrawal.

limitations

Do not generalize to all methylation marks, adult human tissues or a threonine treatment for methylation problems.

nutrient_topic

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

plain_language

A nutrient supply change altered a specific epigenetic mark in this cell model.

primary_references

Influence of threonine metabolism on S-adenosylmethionine and histone methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23118012/ · DOI 10.1126/science.1226603

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism 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 · Mouse stem-cell isotope tracing and culture-medium withdrawal. · source_derived_draft · unverified_draft

## l-threonine-mouse-threonine-methylation A nutrient supply change altered a specific epigenetic mark in this cell model. Threonine withdrawal reduced SAM accumulation and H3K4 trimethylation in mouse embryonic stem cells, with slower growth and increased differentiation. Model: Mouse stem-cell isotope tracing and culture-medium withdrawal. Limitations: Do not generalize to all methylation marks, adult human tissues or a threonine treatment for methylation problems. Evidence access: Primary abstract Influence of threonine metabolism on S-adenosylmethionine and histone methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23118012/ · DOI 10.1126/science.1226603

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

61 genetically confirmed patients versus reference data from 274 controls; stereoselective serine analysis in a smaller subset.

limitations

Association does not identify a unique transport mechanism or justify treating an isolated CSF ratio.

nutrient_topic

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

plain_language

A high amino-acid measurement can accompany a defect in a neighboring pathway.

primary_references

Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35357708/ · DOI 10.1002/jimd.12500

trigger_kind

biomarker_context Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism 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 · 61 genetically confirmed patients versus reference data from 274 controls; stereoselective serine analysis in a smaller subset. · source_derived_draft · unverified_draft

## l-threonine-nkh-amino-acid-pattern A high amino-acid measurement can accompany a defect in a neighboring pathway. Compared with age-adjusted controls, NKH patients had higher CSF threonine, lower serine and higher glycine. Model: 61 genetically confirmed patients versus reference data from 274 controls; stereoselective serine analysis in a smaller subset. Limitations: Association does not identify a unique transport mechanism or justify treating an isolated CSF ratio. Evidence access: Primary abstract Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35357708/ · DOI 10.1002/jimd.12500

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Adipocyte-selective knockout of glycine amidinotransferase in mice

exposure

High-calorie feeding, beta-3 adrenergic activation, and dietary creatine supplementation

limitations

A genetic test of the same cycle with a dietary rescue. It concerns diet-induced thermogenesis rather than cold thermogenesis directly.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse

plain_language

Blocking the cell from making creatine caused obesity, and feeding creatine fixed it.

primary_references

[cold-p28844881] Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity. (2017). https://pubmed.ncbi.nlm.nih.gov/28844881/ DOI: 10.1016/j.cmet.2017.08.009

tissue_or_cell_type

Adipose tissue

trigger_kind

machinery_impairment Imported condition classification; unverified.

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 468–479

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adipocyte-selective knockout of glycine amidinotransferase in mice · source_derived_draft · unverified_draft

### cold-gatm-knockout-obesity Mice lacking the first and rate-limiting enzyme of creatine biosynthesis selectively in fat were prone to diet-induced obesity through suppression of the elevated energy expenditure normally seen with high-calorie feeding, with a blunted capacity for beta-3 adrenergic activation of metabolic rate that was rescued by dietary creatine supplementation. Condition category: machinery_impairment nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Blocking the cell from making creatine caused obesity, and feeding creatine fixed it. organism: Mouse tissue_or_cell_type: Adipose tissue experimental_model: Adipocyte-selective knockout of glycine amidinotransferase in mice limitations: A genetic test of the same cycle with a dietary rescue. It concerns diet-induced thermogenesis rather than cold thermogenesis directly. exposure: High-calorie feeding, beta-3 adrenergic activation, and dietary creatine supplementation evidence_span: {"source_cache": "artifacts/cold-research/28844881.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1341345f147cd7e59119d062b0523a4bf6087a6936b3434bb76a305033a724eb", "start_char": 0, "end_char": 1069, "text_sha256": "1341345f147cd7e59119d062b0523a4bf6087a6936b3434bb76a305033a724eb"} [cold-p28844881] Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity. (2017). https://pubmed.ncbi.nlm.nih.gov/28844881/ DOI: 10.1016/j.cmet.2017.08.009

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

experimental_model

Purified human enzyme; NMR and coupled activity assays

limitations

Whole-body flux contribution remains unquantified.

organism

Homo sapiens

plain_language

SHMT1 can perform the second carnitine-synthesis reaction.

primary_references

[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

tissue_or_cell_type

Cytosolic enzyme tested in vitro

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 177–185

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

### shmt1-html-cleavage Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine. Plain language: SHMT1 can perform the second carnitine-synthesis reaction. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic enzyme tested in vitro experimental_model: Purified human enzyme; NMR and coupled activity assays limitations: Whole-body flux contribution remains unquantified. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

experimental_model

Purified human enzyme kinetic assay

limitations

Mouse Tha1 specialization should not be assigned to a human THA1 enzyme.

organism

Homo sapiens

plain_language

SHMT2 provides another demonstrated aldolase activity.

primary_references

[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

tissue_or_cell_type

Mitochondrial enzyme tested in vitro

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 187–195

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

### shmt2-html-cleavage Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1. Plain language: SHMT2 provides another demonstrated aldolase activity. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial enzyme tested in vitro experimental_model: Purified human enzyme kinetic assay limitations: Mouse Tha1 specialization should not be assigned to a human THA1 enzyme. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3

evidence_span

{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}

experimental_model

Randomized controlled dose-ranging trial

exposure

2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks

limitations

Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.

nutrient_topic

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

organism

Human

plain_language

Adding precursors did not reliably improve redox status in the overall trial.

primary_references

[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

tissue_or_cell_type

114 healthy older volunteers; 20 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1256–1267

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft

### glutathione-glynac-large-ratio-null GlyNAC did not significantly improve the GSH:GSSG ratio; high-dose versus placebo p=0.739. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding precursors did not reliably improve redox status in the overall trial. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

evidence_span

{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}

experimental_model

Randomized controlled dose-ranging trial

exposure

2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks

limitations

Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.

nutrient_topic

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

organism

Human

plain_language

The main trial result must remain visible alongside favorable subsets.

primary_references

[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

tissue_or_cell_type

114 healthy older volunteers; 20 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1269–1280

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft

### glutathione-glynac-large-total-null The primary total-GSH endpoint was not significantly increased; high-dose versus placebo p=0.278. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The main trial result must remain visible alongside favorable subsets. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

evidence_span

{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}

experimental_model

Randomized controlled dose-ranging trial

exposure

2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks

limitations

Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.

nutrient_topic

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

organism

Human

plain_language

A subgroup signal needs confirmation in a prespecified trial.

primary_references

[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

tissue_or_cell_type

114 healthy older volunteers; 20 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1282–1293

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft

### glutathione-glynac-posthoc A post-hoc high-MDA/low-baseline-GSH subgroup had higher total GSH with pooled medium/high doses (p=0.016). Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A subgroup signal needs confirmation in a prespecified trial. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569

evidence_span

{"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"}

experimental_model

Randomized placebo-controlled trial in older adults

exposure

Sixteen-week GlyNAC versus isonitrogenous alanine placebo

limitations

Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm.

nutrient_topic

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

organism

Human

plain_language

Functional signals accompany the biochemical result, with replication still needed.

primary_references

[glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

tissue_or_cell_type

24 older adults randomized 12 per arm; 12 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1308–1319

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial in older adults · source_derived_draft · unverified_draft

### glutathione-glynac-small-function Investigators reported improved physical-function assessments with GlyNAC but not placebo. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Functional signals accompany the biochemical result, with replication still needed. organism: Human tissue_or_cell_type: 24 older adults randomized 12 per arm; 12 young reference participants experimental_model: Randomized placebo-controlled trial in older adults limitations: Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm. exposure: Sixteen-week GlyNAC versus isonitrogenous alanine placebo evidence_span: {"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"} [glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

evidence_span

{"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"}

experimental_model

Randomized placebo-controlled trial in older adults

exposure

Sixteen-week GlyNAC versus isonitrogenous alanine placebo

limitations

Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm.

nutrient_topic

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

organism

Human

plain_language

The small longer trial reported a biochemical benefit.

primary_references

[glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

tissue_or_cell_type

24 older adults randomized 12 per arm; 12 young reference participants

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1295–1306

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial in older adults · source_derived_draft · unverified_draft

### glutathione-glynac-small-gsh The older GlyNAC group improved measured GSH deficiency relative to the placebo pattern. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The small longer trial reported a biochemical benefit. organism: Human tissue_or_cell_type: 24 older adults randomized 12 per arm; 12 young reference participants experimental_model: Randomized placebo-controlled trial in older adults limitations: Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm. exposure: Sixteen-week GlyNAC versus isonitrogenous alanine placebo evidence_span: {"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"} [glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}

experimental_model

Stable-isotope tracer study with before/after supplementation

exposure

Two weeks of glycine/cysteine-precursor supplementation in older participants

limitations

Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.

nutrient_topic

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

organism

Human

plain_language

The measured amount produced also increased.

primary_references

[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

tissue_or_cell_type

Eight older and eight younger adults; erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1113–1124

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft

### glutathione-precursor-absolute-synthesis The absolute erythrocyte GSH synthesis rate increased 230.9% after supplementation. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured amount produced also increased. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}

experimental_model

Stable-isotope tracer study with before/after supplementation

exposure

Two weeks of glycine/cysteine-precursor supplementation in older participants

limitations

Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.

nutrient_topic

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

organism

Human

plain_language

A low measured pool increased in this small study.

primary_references

[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

tissue_or_cell_type

Eight older and eight younger adults; erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1126–1137

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft

### glutathione-precursor-pool The older group’s erythrocyte GSH concentration increased 94.6% after supplementation. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low measured pool increased in this small study. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}

experimental_model

Stable-isotope tracer study with before/after supplementation

exposure

Two weeks of glycine/cysteine-precursor supplementation in older participants

limitations

Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.

nutrient_topic

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

organism

Human

plain_language

The fraction of the pool synthesized each day increased.

primary_references

[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

tissue_or_cell_type

Eight older and eight younger adults; erythrocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1100–1111

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft

### glutathione-precursor-synthesis After supplementation, older participants had a 78.8% higher fractional GSH synthesis rate. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fraction of the pool synthesized each day increased. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483

evidence_access

Primary full text

experimental_model

Rat receptor constructs; 1-second 1 mM agonist pulse with 0.05 mM glycine.

limitations

This does not demonstrate brain entry, cognitive benefit or excitotoxicity after oral intake.

nutrient_topic

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

plain_language

L-aspartate can act at a receptor in a controlled electrophysiology experiment.

primary_references

Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295

L-Aspartate: redox transfer, nitrogen partitioning 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 · Rat receptor constructs; 1-second 1 mM agonist pulse with 0.05 mM glycine. · source_derived_draft · unverified_draft

## l-aspartate-nmda-agonism L-aspartate can act at a receptor in a controlled electrophysiology experiment. L-aspartate evoked currents from recombinant rat GluN1/GluN2D receptors expressed in HEK293 cells when glycine was present. Model: Rat receptor constructs; 1-second 1 mM agonist pulse with 0.05 mM glycine. Limitations: This does not demonstrate brain entry, cognitive benefit or excitotoxicity after oral intake. Evidence access: Primary full text Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295

evidence_access

Primary full text

experimental_model

Rat recombinant receptors in HEK293 cells; voltage-clamp and structural comparisons.

limitations

Not a universal rank of potency or toxicity across all NMDA receptor subtypes.

nutrient_topic

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

plain_language

Two agonists at the same receptor can produce different signal durations.

primary_references

Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295

L-Aspartate: redox transfer, nitrogen partitioning 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 · Rat recombinant receptors in HEK293 cells; voltage-clamp and structural comparisons. · source_derived_draft · unverified_draft

## l-aspartate-nmda-deactivation Two agonists at the same receptor can produce different signal durations. L-aspartate-evoked GluN1/GluN2D currents deactivated faster than L-glutamate-evoked currents under matched recording conditions. Model: Rat recombinant receptors in HEK293 cells; voltage-clamp and structural comparisons. Limitations: Not a universal rank of potency or toxicity across all NMDA receptor subtypes. Evidence access: Primary full text Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295

experimental_model

Cell metabolomics

exposure

Engineered ALDH1L1 expression.

limitations

Pool changes alone do not quantify compartment-specific SHMT 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

plain_language

Changing folate-carbon disposal reshaped amino-acid pools.

primary_references

[sasaki-2023] One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression (2023). https://pubmed.ncbi.nlm.nih.gov/37596270/ DOI: 10.1038/s41598-023-38142-5

tissue_or_cell_type

HuH-7 cells

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1084–1094

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

### aldh1l1-serine-glycine ALDH1L1-expressing HuH-7 cells had lower serine and higher glycine than controls. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing folate-carbon disposal reshaped amino-acid pools. organism: Homo sapiens tissue_or_cell_type: HuH-7 cells experimental_model: Cell metabolomics limitations: Pool changes alone do not quantify compartment-specific SHMT flux. exposure: Engineered ALDH1L1 expression. [sasaki-2023] One-carbon metabolizing enzyme ALDH1L1 influences mitochondrial metabolism through 5-aminoimidazole-4-carboxamide ribonucleotide accumulation and serine depletion, contributing to tumor suppression (2023). https://pubmed.ncbi.nlm.nih.gov/37596270/ DOI: 10.1038/s41598-023-38142-5

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Human FPGS isoforms in Chinese hamster AUXB1 cells

exposure

Mitochondrial FPGS reconstitution with nutrient complementation

limitations

Growth complementation is indirect evidence of glycine synthetic capacity.

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

Restoring mitochondrial folate retention restored glycine independence.

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 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 315–325

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-mito-glycine-complementation Mitochondrial-only FPGS expression relieved the glycine supplementation requirement of AUXB1 cells. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring mitochondrial folate retention restored glycine independence. organism: Human enzyme in Cricetulus griseus cells tissue_or_cell_type: AUXB1 cells experimental_model: Human FPGS isoforms in Chinese hamster AUXB1 cells limitations: Growth complementation is indirect evidence of glycine synthetic capacity. exposure: Mitochondrial FPGS reconstitution with nutrient complementation [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

experimental_model

Native rat liver and bacterially expressed rat GNMT.

limitations

Does not quantify whole-body methyl demand.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Rattus norvegicus

plain_language

GNMT spends a SAM methyl group on glycine.

primary_references

[luka-2008] Acetylation of N-terminal valine of glycine N-methyltransferase affects enzyme inhibition by folate (2008). https://pubmed.ncbi.nlm.nih.gov/18501206/ DOI: 10.1016/j.bbapap.2008.04.016

tissue_or_cell_type

Native/recombinant rat enzyme

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 756–765

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Native rat liver and bacterially expressed rat GNMT. · source_derived_draft · unverified_draft

### folate-methyl-gnmt-methyl-use Rat GNMT activity assays measured SAM-dependent glycine methylation to sarcosine. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: GNMT spends a SAM methyl group on glycine. organism: Rattus norvegicus tissue_or_cell_type: Native/recombinant rat enzyme experimental_model: Native rat liver and bacterially expressed rat GNMT. limitations: Does not quantify whole-body methyl demand. [luka-2008] Acetylation of N-terminal valine of glycine N-methyltransferase affects enzyme inhibition by folate (2008). https://pubmed.ncbi.nlm.nih.gov/18501206/ DOI: 10.1016/j.bbapap.2008.04.016

cross_nutrient

Links existing B6-dependent SHMT chemistry to folate flux direction.

experimental_model

Stable-isotope tracing

exposure

Assay conditions described in the linked primary study.

limitations

Not a universal direction across tissues or nutrition states.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Homo sapiens

plain_language

SHMT1 can consume one-carbon units instead of producing them.

primary_references

[ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016

tissue_or_cell_type

HEK293T and HCT116 cells

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 923–934

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

### shmt1-reverse-flux-replete In nutrient-replete HEK293T and HCT116 cells, isotope tracing showed net SHMT1 flux toward serine synthesis. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: SHMT1 can consume one-carbon units instead of producing them. organism: Homo sapiens tissue_or_cell_type: HEK293T and HCT116 cells experimental_model: Stable-isotope tracing limitations: Not a universal direction across tissues or nutrition states. exposure: Assay conditions described in the linked primary study. cross_nutrient: Links existing B6-dependent SHMT chemistry to folate flux direction. [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016