Nutrient chapter

Glycine

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

91 recorded mechanisms · 11 availability situations · 17 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

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.
Human glycine transporter 1 / SLC6A9 → Glycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Human glycine transporter 2 / SLC6A5 → Glycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
GlyT1 and GlyT2 maintained forward transport under the tested elevated intracellular sodium or chloride conditions, consistent with cooperative ion/substrate binding.
Ion/substrate coupling in human GlyT kinetic assays → Forward glycine transport in human GlyT assays source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Deleting mouse Slc6a5 reduced glycinergic miniature inhibitory-current amplitudes in hypoglossal motoneurons and dissociated spinal neurons.
Mouse glycine transporter 2 / Slc6a5 → Mouse glycinergic miniature inhibitory postsynaptic currents source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Four affected individuals from two families had truncating SLC6A9 variants; two tested individuals had mildly elevated CSF glycine with normal serum glycine.
Human truncating SLC6A9 variants → Human GLYT1 disease with CSF/serum glycine discordance source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Human proton-coupled amino acid transporter 2 / SLC36A2 → Human renal glycine and imino-acid reabsorption source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
SLC6A20 mutations accompanied iminoglycinuria when combined with SLC36A2 variants retaining residual transport.
Human imino-acid transporter / SLC6A20 → Phenotype with residual SLC36A2 transport source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The biochemical characterization reported glycine transport by human SLC25A38; human SLC25A38 expression complemented heme-pathway defects in yeast lacking Hem25.
Human SLC25A38 → Glycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Supplementing 5 mM glycine restored heme levels in yeast lacking Hem25 in the reported experiment.
Glycine → Heme content in yeast lacking Hem25 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Glycine alone did not restore hemoglobin in the zebrafish Slc25a38 congenital-sideroblastic-anemia model.
Glycine → Hemoglobin in zebrafish Slc25a38-deficiency model source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Adding folate with glycine restored hemoglobin in the tested zebrafish Slc25a38-deficiency model.
Experimental glycine plus folate combination → Hemoglobin in zebrafish Slc25a38-deficiency model source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
SLC25A38 loss reduced deuterated-serine incorporation into glycine and glycine-derived glutathione under low-B6 conditions.
Human SLC25A38 → Serine-derived glycine synthesis in human K562 cells source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Formate → Growth of SLC25A38-null human K562 cells source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Reducing Gldc expression in mice suppressed glycine cleavage and depleted one-carbon-bearing folates while glycine accumulated.
Mouse glycine decarboxylase / Gldc → One-carbon-bearing folates in Gldc-deficient mice source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Formate treatment normalized folate profiles, restored embryonic growth and prevented neural-tube defects in the tested Gldc-deficient mice.
Formate → Embryonic development in Gldc-deficient mice source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Glycine → Glycine carbon incorporation into purines in human LOX IMVI cells source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
SHMT2 silencing combined with removal of extracellular glycine halted LOX IMVI proliferation; adding glycine restored growth whereas formate did not.
SHMT2 → Human LOX IMVI cell proliferation source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Removing extracellular glycine alone slowed LOX IMVI proliferation but did not impair A498 cells in the same study.
Glycine-free culture medium → Human LOX IMVI cell proliferation source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Glycine → L-Serine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
With serine absent, higher glycine concentrations inhibited growth and glycine was converted to serine, a reaction consuming one-carbon units.
Glycine → Glycine-to-serine conversion in serine-deprived cancer cultures source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Formate restored nucleotide synthesis and growth in glycine-fed cells lacking serine.
Formate → Growth of glycine-fed serine-deprived cancer cultures source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Glycine opened recombinant human alpha1 homomeric glycine receptors in HEK293 cells; rapid-application and single-channel assays resolved activation kinetics.
Glycine → Human alpha1 homomeric glycine receptor source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Glycine → Human alpha1 homomeric glycine receptor source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human alpha1(K276E)/beta receptors expressed in Xenopus oocytes were about 29-fold less glycine-sensitive than wild type and had shorter channel openings.
Human alpha1(K276E)/beta glycine receptor → Human glycine-receptor response to glycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Glycine → Recombinant GPR158 in the 2023 binding/signaling assays source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Glycine slowed G-alpha-o deactivation only when GPR158 was coexpressed with RGS7/G-beta5, supporting inhibition of the complex's GTPase-accelerating activity.
Glycine → GPR158-associated RGS7/G-beta5 assay complex source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Added glycine reduced cAMP in GPR158-expressing U87 and HEK293 assays; coexpression of RGS7/G-beta5 strengthened the response.
Recombinant GPR158 in the 2023 binding/signaling assays → cAMP reduction in GPR158-expressing cells source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Taurine competed for GPR158 glycine binding and produced weaker cAMP suppression than glycine in the recombinant assays.
Taurine → Recombinant GPR158 in the 2023 binding/signaling assays source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Bath glycine at 1 mM increased layer-II/III prefrontal neuronal excitability in control mice but not Gpr158-knockout mice under synaptic receptor blockade.
Mouse metabotropic glycine receptor / Gpr158 → Glycine-evoked mouse prefrontal neuronal excitability source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Glycine → Potassium M-current in mouse accumbens medium spiny neurons source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
PKA/ERK signaling in mouse accumbens neurons → Glycine-sensitive excitability in mouse accumbens neurons source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Recombinant human GLYAT variants conjugated glycine to benzoyl-CoA in kinetic assays, forming the glycine-conjugation product hippurate.
Human glycine N-acyltransferase / GLYAT → Hippuric acid / benzoylglycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Human GLYAT N156S/R199C haplotype → Human GLYAT benzoyl-CoA turnover source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified GLYAT formed N-isovalerylglycine from isovaleryl-CoA and glycine in vitro, with lower affinity than for its preferred substrate.
Human glycine N-acyltransferase / GLYAT → N-Isovalerylglycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified GLYATL1 also supported N-isovalerylglycine formation in vitro, less favorably than its preferred substrate reaction.
Human glycine N-acyltransferase-like 1 / GLYATL1 → N-Isovalerylglycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Increasing glycine did not increase N-isovalerylglycine formation in the reported in-vitro conjugation experiments.
Glycine → N-Isovalerylglycine source_derived_draftungraded
Experimental context and source evidence
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
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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
Complete structured claim and evidence
During sodium-benzoate treatment of five neonatal-onset nonketotic-hyperglycinemia patients, three of four tested had plasma carnitine deficiency and benzoylcarnitine was detected.
Sodium benzoate → Carnitine depletion during benzoate treatment of nonketotic hyperglycinemia source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
L-carnitine treatment normalized plasma free carnitine in the reported benzoate-treated patients; increased glycine conjugation was a tendency rather than a definitive outcome.
L-Carnitine → Free plasma carnitine in benzoate-treated patients source_derived_draftungraded
Experimental context and source evidence
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
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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
Complete structured claim and evidence
Glycine at 1 mM nearly prevented the calcium rise elicited by 10 micrograms/mL LPS in cultured rat Kupffer cells.
Glycine → LPS-evoked calcium rise in rat Kupffer cells source_derived_draftungraded
Experimental context and source evidence
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
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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
Complete structured claim and evidence
Chloride-free buffer abolished the reported glycine effect, and 1 micromolar strychnine reversed it; glycine hyperpolarized the tested Kupffer cells.
Chloride ion → Chloride-dependent glycine response in rat Kupffer cells source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Glycine reduced LPS-associated TNF-alpha production in cultured rat Kupffer cells.
Glycine → TNF-alpha output from LPS-stimulated rat Kupffer cells source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Glycine → Plasma membrane rupture in mouse macrophages source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
In primary human macrophages, 50 mM glycine inhibited pyroptosis-associated NINJ1 clustering and membrane rupture; NINJ1 knockdown produced a similar rupture phenotype.
Glycine → Human ninjurin-1 / NINJ1 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human pyroptotic macrophages protected from rupture by glycine still lost mitochondrial membrane potential and ATP.
Glycine → Energy viability in pyroptotic human macrophages source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Glycine did not protect primary human macrophages from the tested zVAD/BV6/TNF-induced necroptotic rupture.
Glycine → Necroptotic rupture in human macrophages source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
GARS1 catalyzes glycyl-tRNA formation for glycine incorporation into cytosolic and mitochondrial proteins.
Human glycyl-tRNA synthetase / GARS1 → Human glycyl-tRNA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
A patient with compound GARS variants had tissue respiratory-chain deficiencies and reduced GARS/complex-IV protein in fibroblasts.
Human compound GARS1 T268I/R412C genotype → Human GARS1-associated respiratory-chain dysfunction source_derived_draftungraded
Experimental context and source evidence
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.
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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
Complete structured claim and evidence
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.
Glycine → Type-II collagen production by bovine articular chondrocytes source_derived_draftungraded
Experimental context and source evidence
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
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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
Complete structured claim and evidence
Glycine increased cutaneous blood flow and promoted sleep in the rat experiments; SCN ablation abolished the reported sleep-promoting and hypothermic responses.
Glycine → SCN-dependent heat loss and sleep response in rats source_derived_draftungraded
Experimental context and source evidence
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
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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
Complete structured claim and evidence
NMDA-receptor antagonists blocked glycine-associated cutaneous blood-flow responses in the rat experiments, whereas strychnine did not.
NMDA-receptor signaling in the rat SCN → SCN-dependent heat loss and sleep response in rats source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
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.
Glycine → Performance after partial sleep restriction in the glycine study source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT1 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT2 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified chicken glycine decarboxylase contained approximately one PLP molecule per subunit.
PLP → Chicken glycine decarboxylase source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified chicken liver mitochondrial P-protein
limitations
Chicken enzyme; not a direct assay of human GLDC.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Gallus gallus
plain_language
This avian glycine-cleaving enzyme carries active B6.
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 648–657
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-plp Purified chicken glycine decarboxylase contained approximately one PLP molecule per subunit. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This avian glycine-cleaving enzyme carries active B6. organism: Gallus gallus tissue_or_cell_type: Chicken liver mitochondrial protein experimental_model: Purified chicken liver mitochondrial P-protein limitations: Chicken enzyme; not a direct assay of human GLDC. [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
Complete structured claim and evidence
Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold.
Chicken glycine decarboxylase → Glycine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein.
Human aminomethyltransferase / glycine-cleavage T-protein → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry.
experimental_model
Purified human AMT structures and mutational analyses
limitations
AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step.
primary_references
[b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 682–692
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human AMT structures and mutational analyses · source_derived_draft · unverified_draft
### b6-met-amt-onecarbon Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human AMT structures and mutational analyses limitations: AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux. cross_nutrient: B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry. [b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
Complete structured claim and evidence
Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.
DLD → Protein-bound reduced dihydrolipoyl-lysine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.
evidence
[{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
experimental_model
Human DLD crystallography with NAD+ and NADH.
limitations
Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.
nutrient
Thiamine (vitamin B1) · Thiamine (vitamin B1)
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.
primary_references
[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
tissue_or_cell_type
Purified enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft
### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
Complete structured claim and evidence
LIAS installs sulfur at carbon 6 and carbon 8 of an octanoyl-lysyl residue on GCSH.
Lipoic acid synthetase / LIAS → LIAS sulfur insertion into octanoyl-GCSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"}
experimental_model
X-ray structures of catalytic stages with human lipoyl synthase
exposure
Structural trapping of sulfur-insertion intermediates
limitations
Structural snapshots establish reaction intermediates, not clinical nutrient requirements.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human recombinant proteins
plain_language
LIAS turns the attached precursor into a sulfur-bearing working cofactor.
primary_references
[ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
tissue_or_cell_type
LIAS and H-protein substrate
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 260–271
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of catalytic stages with human lipoyl synthase · source_derived_draft · unverified_draft
### ala-lias-sulfur-installation LIAS installs sulfur at carbon 6 and carbon 8 of an octanoyl-lysyl residue on GCSH. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: LIAS turns the attached precursor into a sulfur-bearing working cofactor. organism: Human recombinant proteins tissue_or_cell_type: LIAS and H-protein substrate experimental_model: X-ray structures of catalytic stages with human lipoyl synthase limitations: Structural snapshots establish reaction intermediates, not clinical nutrient requirements. exposure: Structural trapping of sulfur-insertion intermediates evidence_span: {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"} [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
Complete structured claim and evidence
GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine.
Human mitochondrial glutaredoxin 5 / GLRX5 → Glycine accumulation in lipoylation disorders source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"}
experimental_model
Variant nonketotic hyperglycinemia cohort and cell complementation
exposure
LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells
limitations
Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves.
primary_references
[ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
tissue_or_cell_type
Eight genetically explained patients within an eleven-person group
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 533–544
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Variant nonketotic hyperglycinemia cohort and cell complementation · source_derived_draft · unverified_draft
### ala-glrx5-glycine-failure GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves. organism: Human tissue_or_cell_type: Eight genetically explained patients within an eleven-person group experimental_model: Variant nonketotic hyperglycinemia cohort and cell complementation limitations: Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders. exposure: LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells evidence_span: {"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"} [ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
Complete structured claim and evidence
Despite LIPT1 deficiency, H-protein lipoylation, glycine-cleavage activity and glycine concentrations were normal in this case.
Human lipoyl amidotransferase / LIPT1 → Glycine cleavage flux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"}
experimental_model
Affected patient, biochemical testing and complementation
exposure
Compound-heterozygous LIPT1 variants
limitations
Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
The glycine pathway can keep working when a later transfer step fails.
primary_references
[ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
tissue_or_cell_type
Patient-derived cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 468–479
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected patient, biochemical testing and complementation · source_derived_draft · unverified_draft
### ala-lipt1-glycine-spared Despite LIPT1 deficiency, H-protein lipoylation, glycine-cleavage activity and glycine concentrations were normal in this case. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glycine pathway can keep working when a later transfer step fails. organism: Human tissue_or_cell_type: Patient-derived cells experimental_model: Affected patient, biochemical testing and complementation limitations: Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency. exposure: Compound-heterozygous LIPT1 variants evidence_span: {"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"} [ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
Complete structured claim and evidence
Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide.
Human erythroid aminolevulinate synthase 2 / ALAS2 → 5-Aminolevulinate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
At 10 nM extracellular PN, SLC25A38-null K562 mitochondria had about 3.9-fold lower PLP despite no whole-cell depletion.
Human SLC25A38 knockout genotype → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Supplementary Figure 3E-F
experimental_model
Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.
exposure
10 nM PN culture condition.
limitations
Not proof that SLC25A38 directly transports PLP.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A normal whole-cell pool can hide mitochondrial depletion.
primary_references
[pena2025] 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
tissue_or_cell_type
K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 452–463
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. · source_derived_draft · unverified_draft
### b6-transport-slc25a38-pools At 10 nM extracellular PN, SLC25A38-null K562 mitochondria had about 3.9-fold lower PLP despite no whole-cell depletion. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal whole-cell pool can hide mitochondrial depletion. organism: Homo sapiens tissue_or_cell_type: K562 cells experimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. limitations: Not proof that SLC25A38 directly transports PLP. exposure: 10 nM PN culture condition. evidence_location: Supplementary Figure 3E-F [pena2025] 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
Complete structured claim and evidence
After a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria.
Human SLC25A38 knockout genotype → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figure 4A-B
experimental_model
Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.
exposure
100 nM D3-PN, one-hour tracing after 10 nM PN conditioning.
limitations
Import, retention and indirect regulation remain alternatives.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Synthesis persisted while mitochondrial accumulation failed.
primary_references
[pena2025] 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
tissue_or_cell_type
K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 465–476
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. · source_derived_draft · unverified_draft
### b6-transport-slc25a38-tracer After a 100 nM D3-PN pulse, labeled PLP appeared in whole cells but scarcely in SLC25A38-null mitochondria. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Synthesis persisted while mitochondrial accumulation failed. organism: Homo sapiens tissue_or_cell_type: K562 cells experimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. limitations: Import, retention and indirect regulation remain alternatives. exposure: 100 nM D3-PN, one-hour tracing after 10 nM PN conditioning. evidence_location: Figure 4A-B [pena2025] 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
Complete structured claim and evidence
R134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back.
Human SLC25A38 Arg134Cys → PLP source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_location
Figures 3F and 4C-D
experimental_model
Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing.
exposure
Variant versus wild-type expression.
limitations
No direct PLP transport conclusion.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A disease-associated variant failed the cellular rescue test.
primary_references
[pena2025] 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
tissue_or_cell_type
K562 cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 478–489
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. · source_derived_draft · unverified_draft
### b6-transport-slc25a38-r134c R134C add-back failed to restore mitochondrial PLP accumulation in SLC25A38-null cells, unlike wild-type add-back. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A disease-associated variant failed the cellular rescue test. organism: Homo sapiens tissue_or_cell_type: K562 cells experimental_model: Human K562 knockout cells, Mito-IP, LC-MS and isotope tracing. limitations: No direct PLP transport conclusion. exposure: Variant versus wild-type expression. evidence_location: Figures 3F and 4C-D [pena2025] 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
Complete structured claim and evidence
Isolated Slc25a32-null embryo mitochondria produced about 10.6% of control labeled formate from [13C2]-glycine over 24 hours.
Slc25a32-null mouse genotype → Mitochondrial glycine-derived formate production source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Mitochondrial-only FPGS expression relieved the glycine supplementation requirement of AUXB1 cells.
Human mitochondrial FPGS isoform → Glycine biosynthesis source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Isolated mouse embryonic mitochondria converted labeled glycine carbon into formate.
Glycine → Formate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Rat GNMT activity assays measured SAM-dependent glycine methylation to sarcosine.
Glycine N-methyltransferase (Rattus norvegicus) → Sarcosine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Folate pentaglutamate produced 50% inhibition of native rat GNMT at 1.3 micromolar.
5-Methyltetrahydrofolate pentaglutamate → Glycine N-methyltransferase (Rattus norvegicus) source_derived_draftungraded
Experimental context and source evidence
experimental_model
Native rat liver and bacterially expressed rat GNMT.
limitations
Not a human circulating threshold.
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
A folate form restrains SAM use by GNMT.
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
Purified liver enzyme
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–776
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-folate-inhibition Folate pentaglutamate produced 50% inhibition of native rat GNMT at 1.3 micromolar. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A folate form restrains SAM use by GNMT. organism: Rattus norvegicus tissue_or_cell_type: Purified liver enzyme experimental_model: Native rat liver and bacterially expressed rat GNMT. limitations: Not a human circulating threshold. [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
Complete structured claim and evidence
Non-acetylated recombinant GNMT required 590 micromolar folate pentaglutamate for 50% inhibition, versus 1.3 micromolar for native acetylated GNMT.
5-Methyltetrahydrofolate pentaglutamate → Glycine N-methyltransferase (Rattus norvegicus) source_derived_draftungraded
Experimental context and source evidence
experimental_model
Native rat liver and bacterially expressed rat GNMT.
limitations
Recombinant potency cannot be directly transferred to liver.
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
Protein modification changed inhibitory sensitivity.
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 versus recombinant rat enzyme
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 778–787
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-acetylation Non-acetylated recombinant GNMT required 590 micromolar folate pentaglutamate for 50% inhibition, versus 1.3 micromolar for native acetylated GNMT. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protein modification changed inhibitory sensitivity. organism: Rattus norvegicus tissue_or_cell_type: Native versus recombinant rat enzyme experimental_model: Native rat liver and bacterially expressed rat GNMT. limitations: Recombinant potency cannot be directly transferred to liver. [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
Complete structured claim and evidence
AGAT catalyzes transfer of an amidino group from arginine to glycine, forming guanidinoacetate and ornithine.
Human glycine amidinotransferase AGAT / GATM → Guanidinoacetate source_derived_draftungraded
Experimental context and source evidence
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"}
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
Complete structured claim and evidence
GAMT transfers a methyl group from S-adenosylmethionine to guanidinoacetate, producing creatine and S-adenosylhomocysteine.
Rat guanidinoacetate methyltransferase / Gamt → Guanidinoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/12079381.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6", "start_char": 0, "end_char": 1161, "text_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6"}
experimental_model
SAH-bound crystal structure and mutagenesis
exposure
SAH-bound structure at 2.5 angstrom resolution
limitations
The crystallized construct lacks 36 N-terminal residues; its dimer arrangement is not assigned universally to native human GAMT.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rat GAMT
plain_language
The second synthesis step spends one SAM methyl group to finish each creatine molecule.
primary_references
[creatine-p12079381] Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12079381/ DOI: 10.1016/s0022-2836(02)00448-5 [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
tissue_or_cell_type
Purified, N-terminally truncated enzyme
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 203–215
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · SAH-bound crystal structure and mutagenesis · source_derived_draft · unverified_draft
### creatine-gamt-methyl-transfer GAMT transfers a methyl group from S-adenosylmethionine to guanidinoacetate, producing creatine and S-adenosylhomocysteine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second synthesis step spends one SAM methyl group to finish each creatine molecule. organism: Rat GAMT tissue_or_cell_type: Purified, N-terminally truncated enzyme experimental_model: SAH-bound crystal structure and mutagenesis limitations: The crystallized construct lacks 36 N-terminal residues; its dimer arrangement is not assigned universally to native human GAMT. exposure: SAH-bound structure at 2.5 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12079381.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6", "start_char": 0, "end_char": 1161, "text_sha256": "4f63981cbaa4b7614a24f0a637893d05f9eff2c2143991404b0a7af1ea6667c6"} [creatine-p12079381] Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase. (2002). https://pubmed.ncbi.nlm.nih.gov/12079381/ DOI: 10.1016/s0022-2836(02)00448-5 [creatine-p11595668] Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate. (2001). https://pubmed.ncbi.nlm.nih.gov/11595668/ DOI: 10.1152/ajpendo.2001.281.5.e1095
Complete structured claim and evidence
Creatine feeding reduced renal AGAT and circulating guanidinoacetate without reducing hepatic GAMT activity or capacity to synthesize creatine from guanidinoacetate.
Creatine → Rat guanidinoacetate methyltransferase / Gamt source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"}
experimental_model
Rat feeding, isolated hepatocytes and in-vivo hepatic balance
exposure
Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments
limitations
Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Rats
plain_language
Feedback mainly limited precursor supply in this rat experiment; it did not switch off every synthesis step.
primary_references
[creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
tissue_or_cell_type
Kidney, liver, plasma and isolated hepatocytes
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 295–306
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat feeding, isolated hepatocytes and in-vivo hepatic balance · source_derived_draft · unverified_draft
### creatine-feedback-spares-gamt-capacity Creatine feeding reduced renal AGAT and circulating guanidinoacetate without reducing hepatic GAMT activity or capacity to synthesize creatine from guanidinoacetate. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Feedback mainly limited precursor supply in this rat experiment; it did not switch off every synthesis step. organism: Rats tissue_or_cell_type: Kidney, liver, plasma and isolated hepatocytes experimental_model: Rat feeding, isolated hepatocytes and in-vivo hepatic balance limitations: Interorgan division of synthesis is established here in rats; this is not proof that human tissues never synthesize both steps locally. exposure: Creatine-fed versus creatine-free conditions; guanidinoacetate and methionine substrate experiments evidence_span: {"source_cache": "artifacts/creatine-research/19017728.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee", "start_char": 0, "end_char": 1599, "text_sha256": "8394bd0e01991356b47a2e57593a5054e565b4020d50226b1331dbb290fc0cee"} [creatine-p19017728] Creatine synthesis: hepatic metabolism of guanidinoacetate and creatine in the rat in vitro and in vivo. (2009). https://pubmed.ncbi.nlm.nih.gov/19017728/ DOI: 10.1152/ajpendo.90547.2008
Complete structured claim and evidence
Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione.
Human glutathione synthetase / GSS → GSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 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
Complete structured claim and evidence
After supplementation, older participants had a 78.8% higher fractional GSH synthesis rate.
Glycine plus cysteine-precursor supplementation in the 2011 tracer study → Human erythrocyte glutathione synthesis rate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The primary total-GSH endpoint was not significantly increased; high-dose versus placebo p=0.278.
Glycine plus N-acetylcysteine in the 114-participant two-week trial → Total blood glutathione in the 114-participant GlyNAC trial source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
GlyNAC did not significantly improve the GSH:GSSG ratio; high-dose versus placebo p=0.739.
Glycine plus N-acetylcysteine in the 114-participant two-week trial → Blood reduced-to-oxidized glutathione ratio in the 114-participant GlyNAC trial source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The older GlyNAC group improved measured GSH deficiency relative to the placebo pattern.
Glycine plus N-acetylcysteine in the 24-older-adult sixteen-week trial → Measured glutathione concentrations in the 24-older-adult GlyNAC trial source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
The same expressed human BAAT also catalyzed glycine conjugation of cholic acid.
Human bile acid-CoA:amino acid N-acyltransferase / BAAT → Glycocholate source_derived_draftungraded
Experimental context and source evidence
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/
Complete structured claim and evidence
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.
Human bile acid-CoA:amino acid N-acyltransferase / BAAT → Human hepatic bile acid amidation source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Taurine-depleted cultured cells accumulated mitochondrial tRNA cmnm5U, whose glycine-derived group replaces the taurine-derived group of tau-m5U.
Glycine → Mitochondrial tRNA 5-carboxymethylaminomethyluridine / cmnm5U34 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine.
(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified untagged human AGXT catalyzed the PLP-dependent reaction alanine + glyoxylate ⇌ pyruvate + glycine; forward and reverse kinetic parameters were measured.
Human peroxisomal alanine:glyoxylate aminotransferase / AGXT → Glyoxylate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Glycine increased opening frequency of NMDA-activated channels in cultured mouse brain neurons, with potentiation detected at 10 nM.
Glycine → Mouse NMDA-type receptors, subunits unresolved source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse cultured neurons and outside-out patch recordings.
limitations
The effect was distinct from strychnine-sensitive glycine receptors; it does not define an oral glycine or glutamate response.
nutrient_topic
L-Glutamate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Glutamate
plain_language
An amino acid usually associated with inhibition can assist an excitatory receptor.
primary_references
Glycine potentiates the NMDA response in cultured mouse brain neurons. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2433595/ · DOI 10.1038/325529a0
L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 234–240
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cultured neurons and outside-out patch recordings. · source_derived_draft · unverified_draft
## glutamate-nmda-glycine An amino acid usually associated with inhibition can assist an excitatory receptor. Glycine increased opening frequency of NMDA-activated channels in cultured mouse brain neurons, with potentiation detected at 10 nM. Model: Mouse cultured neurons and outside-out patch recordings. Limitations: The effect was distinct from strychnine-sensitive glycine receptors; it does not define an oral glycine or glutamate response. Evidence access: Primary abstract Glycine potentiates the NMDA response in cultured mouse brain neurons. · 1987 · https://pubmed.ncbi.nlm.nih.gov/2433595/ · DOI 10.1038/325529a0
Complete structured claim and evidence
Applied taurine activated recombinant human alpha1 homomeric glycine receptors in oocytes and HEK293 cells; its potency and efficacy varied with the experimental receptor response.
Taurine → Human alpha1 homomeric glycine receptor source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Applied taurine also activated human alpha2 homomeric glycine receptors, with efficacy varying from weak to full agonism across tested conditions.
Taurine → Human alpha2 homomeric glycine receptor source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Kynurenic-acid NMDA-blocking IC50 shifted from about 15 to 235 micromolar when 10 micromolar glycine was present.
Glycine → Rat NMDA-type glutamate receptors, subunits unresolved source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Spermidine uptake through the tested NMDA receptors required glycine and glutamate.
Glycine → GluN1/GluN2A or GluN1/GluN2B NMDA receptor permeation assay; construct species unresolved source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified bovine pituitary PAL catalyzed amidation of N-acetyl-Tyr-Val-alpha-hydroxyglycine, with reported Km 38 micromolar and turnover 220/s for this synthetic intermediate.
Bovine PAM peptidyl-alpha-hydroxyglycine alpha-amidating lyase domain → N-acetyl-Tyr-Val-alpha-hydroxyglycine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Purified bovine pituitary PAL and bovine-domain expression constructs in HEK293 cells
exposure
Purified PAL with N-acetyl-Tyr-Val-alpha-hydroxyglycine; PHM or PAL-containing constructs expressed in HEK293.
limitations
Kinetics belong to this substrate and preparation. PAL is not another ascorbate-consuming hydroxylase; metal inhibition/reactivation in this paper does not establish physiological metal occupancy.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Bos taurus (protein); Homo sapiens (expression host)
plain_language
After hydroxylation, a second enzyme domain releases the finished peptide amide.
primary_references
[pal1991] Peptidyl-alpha-hydroxyglycine alpha-amidating lyase. Purification, characterization, and expression. (1991). https://pubmed.ncbi.nlm.nih.gov/1902227/ DOI: 10.1016/s0021-9258(20)89524-6
tissue_or_cell_type
Bovine neurointermediate pituitary; heterologous HEK293
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 898–909
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified bovine pituitary PAL and bovine-domain expression constructs in HEK293 cells · source_derived_draft · unverified_draft
### vc-enzyme-pal-intermediate-cleavage Purified bovine pituitary PAL catalyzed amidation of N-acetyl-Tyr-Val-alpha-hydroxyglycine, with reported Km 38 micromolar and turnover 220/s for this synthetic intermediate. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: After hydroxylation, a second enzyme domain releases the finished peptide amide. organism: Bos taurus (protein); Homo sapiens (expression host) tissue_or_cell_type: Bovine neurointermediate pituitary; heterologous HEK293 experimental_model: Purified bovine pituitary PAL and bovine-domain expression constructs in HEK293 cells limitations: Kinetics belong to this substrate and preparation. PAL is not another ascorbate-consuming hydroxylase; metal inhibition/reactivation in this paper does not establish physiological metal occupancy. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Purified PAL with N-acetyl-Tyr-Val-alpha-hydroxyglycine; PHM or PAL-containing constructs expressed in HEK293. [pal1991] Peptidyl-alpha-hydroxyglycine alpha-amidating lyase. Purification, characterization, and expression. (1991). https://pubmed.ncbi.nlm.nih.gov/1902227/ DOI: 10.1016/s0021-9258(20)89524-6
Complete structured claim and evidence
Under conditions that inactivated hydroxylase-dependent rat PAM amidation, ascorbate did not impair conversion of the pre-hydroxylated dansyl-Tyr-Val-alpha-hydroxyglycine intermediate to its amide.
L-Ascorbate → Recombinant rat type-A 75-kDa peptidylglycine amidating enzyme source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
experimental_model
Recombinant rat type-A 75-kDa PAM, purified enzyme assays
exposure
Time/concentration series of ascorbate, DHA or H2O2; fluorescent peptide substrate or pre-hydroxylated intermediate.
limitations
Distinct-substrate assay localizes the defect; no claim that all PAM domains share the same redox/cofactor dependence.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Rattus norvegicus (protein)
plain_language
Bypassing the damaged hydroxylation step showed that the finishing lyase step still worked.
primary_references
[pam1992] Selective inactivation of the hydroxylase activity of bifunctional rat peptidylglycine alpha-amidating enzyme. (1992). https://pubmed.ncbi.nlm.nih.gov/1567215/ DOI: 10.1016/0003-9861(92)90730-k
tissue_or_cell_type
Cell-free recombinant rat protein
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 924–935
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant rat type-A 75-kDa PAM, purified enzyme assays · source_derived_draft · unverified_draft
### vc-enzyme-pam-lyase-spared Under conditions that inactivated hydroxylase-dependent rat PAM amidation, ascorbate did not impair conversion of the pre-hydroxylated dansyl-Tyr-Val-alpha-hydroxyglycine intermediate to its amide. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bypassing the damaged hydroxylation step showed that the finishing lyase step still worked. organism: Rattus norvegicus (protein) tissue_or_cell_type: Cell-free recombinant rat protein experimental_model: Recombinant rat type-A 75-kDa PAM, purified enzyme assays limitations: Distinct-substrate assay localizes the defect; no claim that all PAM domains share the same redox/cofactor dependence. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Time/concentration series of ascorbate, DHA or H2O2; fluorescent peptide substrate or pre-hydroxylated intermediate. [pam1992] Selective inactivation of the hydroxylase activity of bifunctional rat peptidylglycine alpha-amidating enzyme. (1992). https://pubmed.ncbi.nlm.nih.gov/1567215/ DOI: 10.1016/0003-9861(92)90730-k
Complete structured claim and evidence
Removing the terminal glycine from MOCS2A or URM1 abolished the measured interaction with MOCS3.
Human molybdopterin synthase sulfur carrier / MOCS2A → Human adenylyltransferase and sulfurtransferase / MOCS3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/22453920.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "700833295a22a72be9d0ee74144bfe9249d6266c7fcba7b48330a4b2f2bf9c64", "start_char": 0, "end_char": 1267, "text_sha256": "700833295a22a72be9d0ee74144bfe9249d6266c7fcba7b48330a4b2f2bf9c64"}
experimental_model
Human-cell interaction/localization and purified-protein adenylation/sulfuration
exposure
MOCS2A and URM1 terminal glycine variants
limitations
Shared enzyme does not prove competition for sulfur in ordinary nutrient deficiency.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Homo sapiens
plain_language
The sulfur handoff depends on the receiving protein having the right end.
primary_references
[mo-p22453920] Dual role of the molybdenum cofactor biosynthesis protein MOCS3 in tRNA thiolation and molybdenum cofactor biosynthesis in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/22453920/ DOI: 10.1074/jbc.m112.351429
tissue_or_cell_type
Cytosolic sulfur-transfer pathways
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 469–480
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human-cell interaction/localization and purified-protein adenylation/sulfuration · source_derived_draft · unverified_draft
### mo-mocs3-terminal-glycine Removing the terminal glycine from MOCS2A or URM1 abolished the measured interaction with MOCS3. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sulfur handoff depends on the receiving protein having the right end. organism: Homo sapiens tissue_or_cell_type: Cytosolic sulfur-transfer pathways experimental_model: Human-cell interaction/localization and purified-protein adenylation/sulfuration limitations: Shared enzyme does not prove competition for sulfur in ordinary nutrient deficiency. exposure: MOCS2A and URM1 terminal glycine variants evidence_span: {"source_cache": "artifacts/molybdenum-research/22453920.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "700833295a22a72be9d0ee74144bfe9249d6266c7fcba7b48330a4b2f2bf9c64", "start_char": 0, "end_char": 1267, "text_sha256": "700833295a22a72be9d0ee74144bfe9249d6266c7fcba7b48330a4b2f2bf9c64"} [mo-p22453920] Dual role of the molybdenum cofactor biosynthesis protein MOCS3 in tRNA thiolation and molybdenum cofactor biosynthesis in humans. (2012). https://pubmed.ncbi.nlm.nih.gov/22453920/ DOI: 10.1074/jbc.m112.351429
Complete structured claim and evidence

Availability and dependencies

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

Transmitter supply fails when its recycling transporter is lost

Condition: machinery_impairment · Mouse Slc6a5 is deleted.