Nutrient chapter

L-Serine

L-Serine Independently recorded entity or measured process. Linked claims specify compartment, assay and experimental scope.

76 recorded mechanisms · 13 availability situations · 9 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 PHGDH catalyzes the NAD+-dependent oxidation of 3-phosphoglycerate to phosphohydroxypyruvate, the first step of phosphorylated serine biosynthesis.
Human phosphoglycerate dehydrogenase / PHGDH → 3-Phosphohydroxypyruvate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human PHGDH catalytic-domain structure and enzyme assays.
limitations
The truncated dimeric structure does not define the complete native oligomer.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A glycolysis intermediate can be diverted into serine production.
primary_references
Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). · 2017 · https://pubmed.ncbi.nlm.nih.gov/29262655/ · DOI 10.18632/oncotarget.22327
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 14–20
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human PHGDH catalytic-domain structure and enzyme assays. · source_derived_draft · unverified_draft
## l-serine-phgdh-reaction A glycolysis intermediate can be diverted into serine production. Human PHGDH catalyzes the NAD+-dependent oxidation of 3-phosphoglycerate to phosphohydroxypyruvate, the first step of phosphorylated serine biosynthesis. Model: Recombinant human PHGDH catalytic-domain structure and enzyme assays. Limitations: The truncated dimeric structure does not define the complete native oligomer. Evidence access: Primary abstract Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). · 2017 · https://pubmed.ncbi.nlm.nih.gov/29262655/ · DOI 10.18632/oncotarget.22327
Complete structured claim and evidence
Alanine substitutions at the predicted human PHGDH tetramer interface disrupted assembly, stability and activity for several tested ACT-domain residues.
Human phosphoglycerate dehydrogenase / PHGDH → Human PHGDH folding and catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human recombinant variants; solution biochemistry with AlphaFold and molecular-dynamics model refinement.
limitations
The complete tetramer model is computationally derived; it is not an experimentally solved full-length crystal structure.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The enzyme must fold and assemble correctly as well as receive its cofactor.
primary_references
On the quaternary structure of human D-3-phosphoglycerate dehydrogenase. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39012001/ · DOI 10.1002/pro.5089
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 22–28
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant variants; solution biochemistry with AlphaFold and molecular-dynamics model refinement. · source_derived_draft · unverified_draft
## l-serine-phgdh-assembly The enzyme must fold and assemble correctly as well as receive its cofactor. Alanine substitutions at the predicted human PHGDH tetramer interface disrupted assembly, stability and activity for several tested ACT-domain residues. Model: Human recombinant variants; solution biochemistry with AlphaFold and molecular-dynamics model refinement. Limitations: The complete tetramer model is computationally derived; it is not an experimentally solved full-length crystal structure. Evidence access: Primary abstract On the quaternary structure of human D-3-phosphoglycerate dehydrogenase. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39012001/ · DOI 10.1002/pro.5089
Complete structured claim and evidence
Human PSAT1 transfers nitrogen from glutamate to phosphohydroxypyruvate, producing O-phosphoserine and 2-oxoglutarate in a reversible PLP-dependent reaction.
Human phosphoserine aminotransferase / PSAT1 → O-Phospho-L-serine, free metabolite source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Recombinant human PSAT kinetics and substrate-bound crystal structures.
limitations
This is an enzyme reaction, not evidence that dietary glutamate or B6 is limiting in a particular person.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Glutamate supplies nitrogen while active B6 enables the transfer.
primary_references
L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 30–36
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human PSAT kinetics and substrate-bound crystal structures. · source_derived_draft · unverified_draft
## l-serine-psat-nitrogen Glutamate supplies nitrogen while active B6 enables the transfer. Human PSAT1 transfers nitrogen from glutamate to phosphohydroxypyruvate, producing O-phosphoserine and 2-oxoglutarate in a reversible PLP-dependent reaction. Model: Recombinant human PSAT kinetics and substrate-bound crystal structures. Limitations: This is an enzyme reaction, not evidence that dietary glutamate or B6 is limiting in a particular person. Evidence access: Primary full text L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609
Complete structured claim and evidence
Human PSAT contained a PLP internal aldimine associated with Lys200; glutamate converted the cofactor toward its pyridoxamine-phosphate state during the first half-reaction.
PLP → Human phosphoserine aminotransferase / PSAT1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified human PSAT spectroscopy, substrate addition and crystallography.
limitations
PLP is recycled in catalysis; the experiment does not show one dietary B6 molecule is consumed for each serine made.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The B6 cofactor cycles between forms as it carries amino-group chemistry.
primary_references
L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 38–44
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human PSAT spectroscopy, substrate addition and crystallography. · source_derived_draft · unverified_draft
## l-serine-psat-plp The B6 cofactor cycles between forms as it carries amino-group chemistry. Human PSAT contained a PLP internal aldimine associated with Lys200; glutamate converted the cofactor toward its pyridoxamine-phosphate state during the first half-reaction. Model: Purified human PSAT spectroscopy, substrate addition and crystallography. Limitations: PLP is recycled in catalysis; the experiment does not show one dietary B6 molecule is consumed for each serine made. Evidence access: Primary full text L-serine biosynthesis in the human central nervous system: Structure and function of phosphoserine aminotransferase. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36851825/ · DOI 10.1002/pro.4609
Complete structured claim and evidence
Human phosphoserine phosphatase catalyzes the final, effectively irreversible dephosphorylation step of the phosphorylated serine synthesis pathway.
Human phosphoserine phosphatase / PSPH → L-Serine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human PSPH functional analysis.
limitations
Free phosphoserine is distinct from a phosphorylated serine residue in a protein.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The last enzyme releases free serine from its phosphorylated precursor.
primary_references
Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 46–52
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human PSPH functional analysis. · source_derived_draft · unverified_draft
## l-serine-psph-final-step The last enzyme releases free serine from its phosphorylated precursor. Human phosphoserine phosphatase catalyzes the final, effectively irreversible dephosphorylation step of the phosphorylated serine synthesis pathway. Model: Recombinant human PSPH functional analysis. Limitations: Free phosphoserine is distinct from a phosphorylated serine residue in a protein. Evidence access: Primary abstract Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
Complete structured claim and evidence
Human PSPH uses an active-site Mg2+ ion; replacing it with Ca2+ changes coordination of catalytic Asp20 in a way that impedes nucleophilic attack.
Mg2+ → Human phosphoserine phosphatase / PSPH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human enzyme crystallography; the calcium-bound structure used 0.7 M CaCl2 crystallization conditions.
limitations
The high-calcium structure does not establish inhibition by normal dietary calcium.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Two minerals can bind differently to the same enzyme.
primary_references
How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15291819/ · DOI 10.1111/j.0014-2956.2004.04277.x
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 54–60
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme crystallography; the calcium-bound structure used 0.7 M CaCl2 crystallization conditions. · source_derived_draft · unverified_draft
## l-serine-psph-metal Two minerals can bind differently to the same enzyme. Human PSPH uses an active-site Mg2+ ion; replacing it with Ca2+ changes coordination of catalytic Asp20 in a way that impedes nucleophilic attack. Model: Human enzyme crystallography; the calcium-bound structure used 0.7 M CaCl2 crystallization conditions. Limitations: The high-calcium structure does not establish inhibition by normal dietary calcium. Evidence access: Primary abstract How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase. · 2004 · https://pubmed.ncbi.nlm.nih.gov/15291819/ · DOI 10.1111/j.0014-2956.2004.04277.x
Complete structured claim and evidence
The 2024 human PSPH study found near-saturation with Mg2+ under physiological conditions and judged ordinary Mg2+/Ca2+ fluctuations unlikely to regulate activity substantially.
Human phosphoserine phosphatase / PSPH → Mg2+ source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified human wild-type and variant PSPH; kinetic interpretation of physiological ion ranges.
limitations
This qualifies physiological extrapolation from binding assays; it does not deny the earlier calcium-bound structure.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A required mineral need not be the rate-limiting input when its binding site is already occupied.
primary_references
Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 62–68
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human wild-type and variant PSPH; kinetic interpretation of physiological ion ranges. · source_derived_draft · unverified_draft
## l-serine-psph-physiology A required mineral need not be the rate-limiting input when its binding site is already occupied. The 2024 human PSPH study found near-saturation with Mg2+ under physiological conditions and judged ordinary Mg2+/Ca2+ fluctuations unlikely to regulate activity substantially. Model: Purified human wild-type and variant PSPH; kinetic interpretation of physiological ion ranges. Limitations: This qualifies physiological extrapolation from binding assays; it does not deny the earlier calcium-bound structure. Evidence access: Primary abstract Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
Complete structured claim and evidence
Serine inhibited isolated PSPH, but this inhibition did not control flux through the reconstructed phosphorylated pathway unless PSPH activity was severely impaired.
L-Serine → Human phosphoserine phosphatase / PSPH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human enzyme assays and pathway-flux analysis.
limitations
Pathway reconstruction is not a measurement of all tissues in vivo.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Feedback measured on one enzyme need not control the whole pathway.
primary_references
Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 70–76
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme assays and pathway-flux analysis. · source_derived_draft · unverified_draft
## l-serine-psph-feedback Feedback measured on one enzyme need not control the whole pathway. Serine inhibited isolated PSPH, but this inhibition did not control flux through the reconstructed phosphorylated pathway unless PSPH activity was severely impaired. Model: Human enzyme assays and pathway-flux analysis. Limitations: Pathway reconstruction is not a measurement of all tissues in vivo. Evidence access: Primary abstract Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
Complete structured claim and evidence
The A35T PSPH substitution reduced catalytic efficiency about fiftyfold and lowered thermal stability; M52T had milder effects and D32N behaved like wild type in these assays.
Human phosphoserine phosphatase / PSPH → Human PSPH A35T catalytic function source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Recombinant human natural variants.
limitations
Assay behavior does not independently resolve the clinical pathogenicity of every variant.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Different variants in the same gene can have very different biochemical effects.
primary_references
Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 78–84
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human natural variants. · source_derived_draft · unverified_draft
## l-serine-psph-variant Different variants in the same gene can have very different biochemical effects. The A35T PSPH substitution reduced catalytic efficiency about fiftyfold and lowered thermal stability; M52T had milder effects and D32N behaved like wild type in these assays. Model: Recombinant human natural variants. Limitations: Assay behavior does not independently resolve the clinical pathogenicity of every variant. Evidence access: Primary abstract Effect of l-serine and magnesium ions on the functional properties of human phosphoserine phosphatase and its pathogenetic variants. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38278334/ · DOI 10.1016/j.bbadis.2024.167034
Complete structured claim and evidence
Patients with inherited PHGDH deficiency had low plasma and cerebrospinal-fluid serine, variably low glycine, microcephaly, seizures and severe developmental impairment.
Human phosphoglycerate dehydrogenase / PHGDH → L-Serine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Five-patient treatment follow-up in a rare inherited disorder.
limitations
This is not evidence that ordinary low dietary intake causes the same syndrome.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
An internal synthesis defect can create a clinically important shortage.
primary_references
Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 86–92
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Five-patient treatment follow-up in a rare inherited disorder. · source_derived_draft · unverified_draft
## l-serine-phgdh-deficiency An internal synthesis defect can create a clinically important shortage. Patients with inherited PHGDH deficiency had low plasma and cerebrospinal-fluid serine, variably low glycine, microcephaly, seizures and severe developmental impairment. Model: Five-patient treatment follow-up in a rare inherited disorder. Limitations: This is not evidence that ordinary low dietary intake causes the same syndrome. Evidence access: Primary abstract Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
Complete structured claim and evidence
Amino-acid therapy over 3–7.5 years reduced seizure frequency in all five reported patients, with two becoming seizure-free; developmental progress was reported in only one early-treated patient.
L-Serine → Seizure outcomes during amino-acid treatment of PHGDH deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Uncontrolled follow-up using different serine/glycine treatment regimens.
limitations
Small heterogeneous case series; no general supplement dose or guaranteed developmental rescue follows.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Restoring supply can help some outcomes without reversing every consequence.
primary_references
Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 94–100
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Uncontrolled follow-up using different serine/glycine treatment regimens. · source_derived_draft · unverified_draft
## l-serine-phgdh-treatment Restoring supply can help some outcomes without reversing every consequence. Amino-acid therapy over 3–7.5 years reduced seizure frequency in all five reported patients, with two becoming seizure-free; developmental progress was reported in only one early-treated patient. Model: Uncontrolled follow-up using different serine/glycine treatment regimens. Limitations: Small heterogeneous case series; no general supplement dose or guaranteed developmental rescue follows. Evidence access: Primary abstract Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
Complete structured claim and evidence
Recombinant PSAT1 Asp100Ala retained only about 15% of wild-type maximal activity in the study of two affected siblings.
Human phosphoserine aminotransferase / PSAT1 → Human PSAT1 Asp100Ala catalytic activity 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 and recombinant mutant expression.
limitations
Fibroblast enzyme testing was inconclusive; the recombinant result is the direct functional measurement.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The amino-group transfer step can become a synthesis bottleneck.
primary_references
Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17436247/ · DOI 10.1086/517888
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 102–108
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human family genetics and recombinant mutant expression. · source_derived_draft · unverified_draft
## l-serine-psat-genetic The amino-group transfer step can become a synthesis bottleneck. Recombinant PSAT1 Asp100Ala retained only about 15% of wild-type maximal activity in the study of two affected siblings. Model: Human family genetics and recombinant mutant expression. Limitations: Fibroblast enzyme testing was inconclusive; the recombinant result is the direct functional measurement. Evidence access: Primary abstract Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17436247/ · DOI 10.1086/517888
Complete structured claim and evidence
Two siblings received serine plus glycine at different ages: the index child treated from 11 weeks died at seven months, whereas the sibling treated from birth had a normal reported outcome at age three.
L-Serine → Clinical outcomes with different treatment timing in PSAT1 deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Two siblings; reported regimens included serine 500 mg/kg/day and glycine 200 mg/kg/day.
limitations
Case comparison is not randomized proof, a universal rescue, or a dosing recommendation.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Timing may matter when early development depends on local amino-acid supply.
primary_references
Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17436247/ · DOI 10.1086/517888
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 110–116
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two siblings; reported regimens included serine 500 mg/kg/day and glycine 200 mg/kg/day. · source_derived_draft · unverified_draft
## l-serine-psat-early-treatment Timing may matter when early development depends on local amino-acid supply. Two siblings received serine plus glycine at different ages: the index child treated from 11 weeks died at seven months, whereas the sibling treated from birth had a normal reported outcome at age three. Model: Two siblings; reported regimens included serine 500 mg/kg/day and glycine 200 mg/kg/day. Limitations: Case comparison is not randomized proof, a universal rescue, or a dosing recommendation. Evidence access: Primary abstract Phosphoserine aminotransferase deficiency: a novel disorder of the serine biosynthesis pathway. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17436247/ · DOI 10.1086/517888
Complete structured claim and evidence
NAXD loss caused NADHX accumulation and impaired de novo serine synthesis in human HAP1 cells under galactose stress and in patient-derived fibroblasts.
Human NAD(P)HX dehydratase / NAXD → Hydrated NADH / NADHX source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human knockout cells, patient fibroblasts and isotope tracing.
limitations
The impairment depended on culture conditions and was more pronounced under galactose stress.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Damaged cofactor can block a pathway even when the enzyme is still present.
primary_references
Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 118–124
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human knockout cells, patient fibroblasts and isotope tracing. · source_derived_draft · unverified_draft
## l-serine-naxd-block Damaged cofactor can block a pathway even when the enzyme is still present. NAXD loss caused NADHX accumulation and impaired de novo serine synthesis in human HAP1 cells under galactose stress and in patient-derived fibroblasts. Model: Human knockout cells, patient fibroblasts and isotope tracing. Limitations: The impairment depended on culture conditions and was more pronounced under galactose stress. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
Complete structured claim and evidence
Purified NADHX species inhibited recombinant human PHGDH, supporting direct inhibition as an explanation for the serine-synthesis defect in NAXD-deficient cells.
Hydrated NADH / NADHX → Human phosphoglycerate dehydrogenase / PHGDH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate.
limitations
NADHX is chemically damaged NADH, not simply a low NAD+ concentration.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Repair of a niacin-derived cofactor protects a separate amino-acid pathway.
primary_references
Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 126–132
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate. · source_derived_draft · unverified_draft
## l-serine-nadhx-inhibition Repair of a niacin-derived cofactor protects a separate amino-acid pathway. Purified NADHX species inhibited recombinant human PHGDH, supporting direct inhibition as an explanation for the serine-synthesis defect in NAXD-deficient cells. Model: Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate. Limitations: NADHX is chemically damaged NADH, not simply a low NAD+ concentration. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
Complete structured claim and evidence
Nicotinamide riboside and inosine partly improved viability of galactose-grown NAXD-null HAP1 cells, with metabolomics suggesting different mechanisms involving serine synthesis.
Nicotinamide riboside → Growth of human NAXD-null HAP1 cells under galactose stress source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human cell add-back experiments.
limitations
Cell rescue is not established treatment for inherited NAXD disease.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Two metabolic inputs partly bypassed a specific cellular vulnerability.
primary_references
Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 134–140
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell add-back experiments. · source_derived_draft · unverified_draft
## l-serine-naxd-small-molecule-rescue Two metabolic inputs partly bypassed a specific cellular vulnerability. Nicotinamide riboside and inosine partly improved viability of galactose-grown NAXD-null HAP1 cells, with metabolomics suggesting different mechanisms involving serine synthesis. Model: Human cell add-back experiments. Limitations: Cell rescue is not established treatment for inherited NAXD disease. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
Complete structured claim and evidence
Purified SFXN1 transported serine in vitro, and human-cell genetic experiments identified it as an inner-mitochondrial-membrane serine transporter.
Human sideroflexin 1 / SFXN1 → L-Serine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human CRISPR screens, localization and purified-protein transport experiments.
limitations
This does not imply SFXN1 is the only transporter or that all cellular serine is mitochondrial.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Serine must cross a compartment boundary before mitochondrial enzymes can use it.
primary_references
SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528
transport_effect
raises Identified as an inner-mitochondrial-membrane serine importer.
transport_pool
the mitochondrial matrix Identified as an inner-mitochondrial-membrane serine importer.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 142–148
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CRISPR screens, localization and purified-protein transport experiments. · source_derived_draft · unverified_draft
## l-serine-sfxn1-import Serine must cross a compartment boundary before mitochondrial enzymes can use it. Purified SFXN1 transported serine in vitro, and human-cell genetic experiments identified it as an inner-mitochondrial-membrane serine transporter. Model: Human CRISPR screens, localization and purified-protein transport experiments. Limitations: This does not imply SFXN1 is the only transporter or that all cellular serine is mitochondrial. Evidence access: Primary abstract SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528
Complete structured claim and evidence
SFXN1-null human cells had impaired glycine and purine synthesis; loss of both SFXN1 and SFXN3 caused stronger defects, including dependence on exogenous glycine.
Human sideroflexin 1 / SFXN1 → Glycine and purine synthesis in human SFXN1-deficient cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cell single and double knockout comparisons.
limitations
Related transporters provide redundancy; this is not a demonstrated dietary serine deficiency.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Transport capacity can limit another amino acid and nucleotide production.
primary_references
SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 150–156
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell single and double knockout comparisons. · source_derived_draft · unverified_draft
## l-serine-sfxn1-loss Transport capacity can limit another amino acid and nucleotide production. SFXN1-null human cells had impaired glycine and purine synthesis; loss of both SFXN1 and SFXN3 caused stronger defects, including dependence on exogenous glycine. Model: Human cell single and double knockout comparisons. Limitations: Related transporters provide redundancy; this is not a demonstrated dietary serine deficiency. Evidence access: Primary abstract SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528
Complete structured claim and evidence
SFXN1 deficiency impaired complex III biogenesis, assembly and activity and compromised coenzyme Q levels.
Human sideroflexin 1 / SFXN1 → Human mitochondrial complex III integrity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cultured-cell mitochondrial carrier characterization.
limitations
This is a transporter-loss experiment, not evidence that serine supplements raise CoQ.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A transport defect can affect the respiratory chain as well as one-carbon metabolism.
primary_references
The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33730581/ · DOI 10.1016/j.celrep.2021.108869
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 158–164
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cultured-cell mitochondrial carrier characterization. · source_derived_draft · unverified_draft
## l-serine-sfxn1-respiration A transport defect can affect the respiratory chain as well as one-carbon metabolism. SFXN1 deficiency impaired complex III biogenesis, assembly and activity and compromised coenzyme Q levels. Model: Human cultured-cell mitochondrial carrier characterization. Limitations: This is a transporter-loss experiment, not evidence that serine supplements raise CoQ. Evidence access: Primary abstract The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33730581/ · DOI 10.1016/j.celrep.2021.108869
Complete structured claim and evidence
The study attributed SFXN1-dependent complex III support to heme and 2-oxoglutarate metabolism rather than to its one-carbon-metabolism role alone.
Human sideroflexin 1 / SFXN1 → Heme and 2-oxoglutarate support of SFXN1-dependent complex III function source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cell metabolic and respiratory-chain experiments.
limitations
This does not reduce all SFXN1 phenotypes to one folate bottleneck.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Two effects of the same transporter can run through different downstream routes.
primary_references
The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33730581/ · DOI 10.1016/j.celrep.2021.108869
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 166–172
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell metabolic and respiratory-chain experiments. · source_derived_draft · unverified_draft
## l-serine-sfxn1-rescue-boundary Two effects of the same transporter can run through different downstream routes. The study attributed SFXN1-dependent complex III support to heme and 2-oxoglutarate metabolism rather than to its one-carbon-metabolism role alone. Model: Human cell metabolic and respiratory-chain experiments. Limitations: This does not reduce all SFXN1 phenotypes to one folate bottleneck. Evidence access: Primary abstract The mitochondrial carrier SFXN1 is critical for complex III integrity and cellular metabolism. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33730581/ · DOI 10.1016/j.celrep.2021.108869
Complete structured claim and evidence
Catalytic SHMT2 loss in human cells impaired mitochondrial tRNA modification and caused preferential ribosome stalling at AAG lysine and UUG leucine codons.
SHMT2 → Human mitochondrial translation at lysine and leucine codons source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human SHMT2 knockout and mitochondrial ribosome profiling.
limitations
The methyl-donor route was mechanistically inferred alongside measured modification and translation defects.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Serine-linked folate chemistry helps mitochondria read particular codons.
primary_references
Mitochondrial translation requires folate-dependent tRNA methylation. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29364879/ · DOI 10.1038/nature25460
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 174–180
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SHMT2 knockout and mitochondrial ribosome profiling. · source_derived_draft · unverified_draft
## l-serine-shmt2-translation Serine-linked folate chemistry helps mitochondria read particular codons. Catalytic SHMT2 loss in human cells impaired mitochondrial tRNA modification and caused preferential ribosome stalling at AAG lysine and UUG leucine codons. Model: Human SHMT2 knockout and mitochondrial ribosome profiling. Limitations: The methyl-donor route was mechanistically inferred alongside measured modification and translation defects. Evidence access: Primary abstract Mitochondrial translation requires folate-dependent tRNA methylation. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29364879/ · DOI 10.1038/nature25460
Complete structured claim and evidence
Serine metabolism supported the methionine cycle through de novo ATP synthesis both with and without extracellular methionine in the tested cancer cells.
L-Serine → Methionine-cycle function in studied human cancer cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cancer-cell metabolic tracing and nutrient manipulation.
limitations
This is not proof that adding serine increases methylation in every tissue.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Methylation needs the ATP-making side of serine metabolism as well as one-carbon donation.
primary_references
Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26774282/ · DOI 10.1016/j.molcel.2015.12.014
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 182–188
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell metabolic tracing and nutrient manipulation. · source_derived_draft · unverified_draft
## l-serine-serine-atp-methylation Methylation needs the ATP-making side of serine metabolism as well as one-carbon donation. Serine metabolism supported the methionine cycle through de novo ATP synthesis both with and without extracellular methionine in the tested cancer cells. Model: Human cancer-cell metabolic tracing and nutrient manipulation. Limitations: This is not proof that adding serine increases methylation in every tissue. Evidence access: Primary abstract Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26774282/ · DOI 10.1016/j.molcel.2015.12.014
Complete structured claim and evidence
Serine starvation increased the methionine/SAM ratio and reduced methyl-group transfer to DNA and RNA; ATP and AMP fell without AMPK activation.
L-Serine → DNA/RNA methyl transfer during serine starvation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cancer-cell starvation experiments.
limitations
No universal oncogene activation, whole-body methylation collapse or dietary threshold is established.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A shortage can alter methylation without a simple energy-sensor response.
primary_references
Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26774282/ · DOI 10.1016/j.molcel.2015.12.014
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 190–196
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell starvation experiments. · source_derived_draft · unverified_draft
## l-serine-serine-starvation-methylation A shortage can alter methylation without a simple energy-sensor response. Serine starvation increased the methionine/SAM ratio and reduced methyl-group transfer to DNA and RNA; ATP and AMP fell without AMPK activation. Model: Human cancer-cell starvation experiments. Limitations: No universal oncogene activation, whole-body methylation collapse or dietary threshold is established. Evidence access: Primary abstract Serine Metabolism Supports the Methionine Cycle and DNA/RNA Methylation through De Novo ATP Synthesis in Cancer Cells. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26774282/ · DOI 10.1016/j.molcel.2015.12.014
Complete structured claim and evidence
Serine withdrawal induced a transient p53–p21 arrest that redirected limited serine toward glutathione synthesis and preserved antioxidant capacity in the tested human cancer cells.
L-Serine → p53-dependent adaptation to serine starvation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cancer-cell starvation with p53 comparisons.
limitations
The response depends on genotype and experimental conditions, not a universal ranking of serine uses.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Cells can reallocate scarce substrate to survival rather than proliferation.
primary_references
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 198–204
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell starvation with p53 comparisons. · source_derived_draft · unverified_draft
## l-serine-starvation-p53 Cells can reallocate scarce substrate to survival rather than proliferation. Serine withdrawal induced a transient p53–p21 arrest that redirected limited serine toward glutathione synthesis and preserved antioxidant capacity in the tested human cancer cells. Model: Human cancer-cell starvation with p53 comparisons. Limitations: The response depends on genotype and experimental conditions, not a universal ranking of serine uses. Evidence access: Primary abstract Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743
Complete structured claim and evidence
p53-deficient cells failed to complete the adaptive response to serine withdrawal and developed oxidative stress, lower viability and impaired proliferation.
Serine starvation in p53-deficient human cancer cells → Oxidative stress during serine starvation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cancer-cell p53 comparison, with an additional in-vivo tumor model.
limitations
This is not a proven dietary cancer therapy.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The same shortage can have a different outcome when stress-response machinery is missing.
primary_references
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 206–212
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell p53 comparison, with an additional in-vivo tumor model. · source_derived_draft · unverified_draft
## l-serine-starvation-p53-loss The same shortage can have a different outcome when stress-response machinery is missing. p53-deficient cells failed to complete the adaptive response to serine withdrawal and developed oxidative stress, lower viability and impaired proliferation. Model: Human cancer-cell p53 comparison, with an additional in-vivo tumor model. Limitations: This is not a proven dietary cancer therapy. Evidence access: Primary abstract Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23242140/ · DOI 10.1038/nature11743
Complete structured claim and evidence
Extracellular serine supported optimal activated T-cell expansion by providing glycine and one-carbon units for nucleotide biosynthesis; adequate glucose alone did not substitute.
L-Serine → Serine-dependent expansion of activated mouse T cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Primary study of activated T cells with in-vivo pathogen-driven expansion experiments in mice.
limitations
Species and activation context limit translation to human supplementation. Correction record: PubMed indexes a published erratum, PMID 28178570 / DOI 10.1016/j.cmet.2017.01.014. The notice body was not accessible during this curation, so its specific scope and impact remain unverified. Do not treat the original study as having received comprehensive integrity clearance. https://pubmed.ncbi.nlm.nih.gov/28178570/
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Fuel availability alone does not meet every requirement for immune-cell division.
primary_references
Serine Is an Essential Metabolite for Effector T Cell Expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28111214/ · DOI 10.1016/j.cmet.2016.12.011
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 214–220
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary study of activated T cells with in-vivo pathogen-driven expansion experiments in mice. · source_derived_draft · unverified_draft
## l-serine-tcell-expansion Fuel availability alone does not meet every requirement for immune-cell division. Extracellular serine supported optimal activated T-cell expansion by providing glycine and one-carbon units for nucleotide biosynthesis; adequate glucose alone did not substitute. Model: Primary study of activated T cells with in-vivo pathogen-driven expansion experiments in mice. Limitations: Species and activation context limit translation to human supplementation. Correction record: PubMed indexes a published erratum, PMID 28178570 / DOI 10.1016/j.cmet.2017.01.014. The notice body was not accessible during this curation, so its specific scope and impact remain unverified. Do not treat the original study as having received comprehensive integrity clearance. https://pubmed.ncbi.nlm.nih.gov/28178570/ Evidence access: Primary abstract Serine Is an Essential Metabolite for Effector T Cell Expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28111214/ · DOI 10.1016/j.cmet.2016.12.011
Complete structured claim and evidence
Dietary serine restriction impaired pathogen-driven T-cell expansion in the mouse experiments without disrupting overall immune-cell homeostasis; formate rescued serine-deprived T cells in culture.
L-Serine → Serine-dependent expansion of activated mouse T cells source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse dietary restriction and separate activated-cell formate add-back.
limitations
The culture rescue is not an in-vivo dietary rescue or a human treatment dose. Correction record: PubMed indexes a published erratum, PMID 28178570 / DOI 10.1016/j.cmet.2017.01.014. The notice body was not accessible during this curation, so its specific scope and impact remain unverified. Do not treat the original study as having received comprehensive integrity clearance. https://pubmed.ncbi.nlm.nih.gov/28178570/
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Shortage can impair an induced response without eliminating resting immune cells.
primary_references
Serine Is an Essential Metabolite for Effector T Cell Expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28111214/ · DOI 10.1016/j.cmet.2016.12.011
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 222–228
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse dietary restriction and separate activated-cell formate add-back. · source_derived_draft · unverified_draft
## l-serine-tcell-restriction Shortage can impair an induced response without eliminating resting immune cells. Dietary serine restriction impaired pathogen-driven T-cell expansion in the mouse experiments without disrupting overall immune-cell homeostasis; formate rescued serine-deprived T cells in culture. Model: Mouse dietary restriction and separate activated-cell formate add-back. Limitations: The culture rescue is not an in-vivo dietary rescue or a human treatment dose. Correction record: PubMed indexes a published erratum, PMID 28178570 / DOI 10.1016/j.cmet.2017.01.014. The notice body was not accessible during this curation, so its specific scope and impact remain unverified. Do not treat the original study as having received comprehensive integrity clearance. https://pubmed.ncbi.nlm.nih.gov/28178570/ Evidence access: Primary abstract Serine Is an Essential Metabolite for Effector T Cell Expansion. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28111214/ · DOI 10.1016/j.cmet.2016.12.011
Complete structured claim and evidence
Serine-derived glycine supported glutathione synthesis required for optimal LPS-induced IL-1beta mRNA expression; inflammasome activation was not the affected step.
L-Serine → Glutathione-dependent IL-1beta transcription in mouse macrophages source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse macrophage metabolic manipulation and LPS stimulation.
limitations
IL-1beta transcription and inflammasome-mediated processing are different endpoints.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
An antioxidant-building pathway can support inflammatory gene expression.
primary_references
Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 230–236
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophage metabolic manipulation and LPS stimulation. · source_derived_draft · unverified_draft
## l-serine-macrophage-gsh An antioxidant-building pathway can support inflammatory gene expression. Serine-derived glycine supported glutathione synthesis required for optimal LPS-induced IL-1beta mRNA expression; inflammasome activation was not the affected step. Model: Mouse macrophage metabolic manipulation and LPS stimulation. Limitations: IL-1beta transcription and inflammasome-mediated processing are different endpoints. Evidence access: Primary abstract Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014
Complete structured claim and evidence
Cell-permeable glutathione, but not formate, rescued IL-1beta mRNA expression under serine restriction in the macrophage experiments.
GSH → Glutathione-dependent IL-1beta transcription in mouse macrophages source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Macrophage culture with serine restriction and metabolite add-back.
limitations
The delivered compound was cell-permeable GSH, not an assumed effect of oral glutathione.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The limiting branch differs from the nucleotide requirement in dividing T cells.
primary_references
Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 238–244
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Macrophage culture with serine restriction and metabolite add-back. · source_derived_draft · unverified_draft
## l-serine-macrophage-rescue The limiting branch differs from the nucleotide requirement in dividing T cells. Cell-permeable glutathione, but not formate, rescued IL-1beta mRNA expression under serine restriction in the macrophage experiments. Model: Macrophage culture with serine restriction and metabolite add-back. Limitations: The delivered compound was cell-permeable GSH, not an assumed effect of oral glutathione. Evidence access: Primary abstract Serine Metabolism Supports Macrophage IL-1β Production. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30773464/ · DOI 10.1016/j.cmet.2019.01.014
Complete structured claim and evidence
Purified human PSS1 reconstituted with phosphatidylcholine showed serine base-exchange activity producing phosphatidylserine.
Human phosphatidylserine synthase 1 / PTDSS1 → Phosphatidylserine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human PSS1 proteoliposomes with POPC and radioactive serine assays.
limitations
The bound endogenous lipid density could not conclusively distinguish PC from PE; no universal exclusion of PE is asserted.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Serine can replace a phospholipid headgroup to make a different membrane lipid.
primary_references
Structural basis for catalytic mechanism of human phosphatidylserine synthase 1. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40044636/ · DOI 10.1038/s41421-025-00775-3
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 246–252
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PSS1 proteoliposomes with POPC and radioactive serine assays. · source_derived_draft · unverified_draft
## l-serine-pss1-exchange Serine can replace a phospholipid headgroup to make a different membrane lipid. Purified human PSS1 reconstituted with phosphatidylcholine showed serine base-exchange activity producing phosphatidylserine. Model: Human PSS1 proteoliposomes with POPC and radioactive serine assays. Limitations: The bound endogenous lipid density could not conclusively distinguish PC from PE; no universal exclusion of PE is asserted. Evidence access: Primary full text Structural basis for catalytic mechanism of human phosphatidylserine synthase 1. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40044636/ · DOI 10.1038/s41421-025-00775-3
Complete structured claim and evidence
Human PSS1 structures positioned calcium and serine in the catalytic pocket; structural and mutational analysis implicated His172 in the base-exchange mechanism.
Calcium ion → Human phosphatidylserine synthase 1 / PTDSS1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Full-length human PSS1 cryo-EM in apo, calcium-bound and calcium/serine-bound states.
limitations
The proposed chemical mechanism combines structure and mutagenesis; it is not a clinical calcium-response experiment.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Calcium has a constructive catalytic role in this lipid-building enzyme.
primary_references
Structural basis for catalytic mechanism of human phosphatidylserine synthase 1. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40044636/ · DOI 10.1038/s41421-025-00775-3
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 254–260
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Full-length human PSS1 cryo-EM in apo, calcium-bound and calcium/serine-bound states. · source_derived_draft · unverified_draft
## l-serine-pss1-calcium Calcium has a constructive catalytic role in this lipid-building enzyme. Human PSS1 structures positioned calcium and serine in the catalytic pocket; structural and mutational analysis implicated His172 in the base-exchange mechanism. Model: Full-length human PSS1 cryo-EM in apo, calcium-bound and calcium/serine-bound states. Limitations: The proposed chemical mechanism combines structure and mutagenesis; it is not a clinical calcium-response experiment. Evidence access: Primary full text Structural basis for catalytic mechanism of human phosphatidylserine synthase 1. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40044636/ · DOI 10.1038/s41421-025-00775-3
Complete structured claim and evidence
PTDSS1 variants from Lenz-Majewski syndrome markedly reduced product inhibition by phosphatidylserine and increased phosphatidylserine synthesis in patient fibroblasts.
Phosphatidylserine → Human phosphatidylserine synthase 1 / PTDSS1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human genetics and patient fibroblast synthesis assays.
limitations
These gain-of-function variants are not serine shortage or proof of an effect from phosphatidylserine supplements.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Failure of a feedback brake can increase lipid production.
primary_references
Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24241535/ · DOI 10.1038/ng.2829
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 262–268
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human genetics and patient fibroblast synthesis assays. · source_derived_draft · unverified_draft
## l-serine-pss1-feedback Failure of a feedback brake can increase lipid production. PTDSS1 variants from Lenz-Majewski syndrome markedly reduced product inhibition by phosphatidylserine and increased phosphatidylserine synthesis in patient fibroblasts. Model: Human genetics and patient fibroblast synthesis assays. Limitations: These gain-of-function variants are not serine shortage or proof of an effect from phosphatidylserine supplements. Evidence access: Primary abstract Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24241535/ · DOI 10.1038/ng.2829
Complete structured claim and evidence
Among 125 MacTel type 2 patients without pathogenic SPT variants and 94 controls, circulating serine was lower and deoxysphingolipids higher in the patient group.
L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human case-control metabolomics; serine 20.6% lower and deoxysphingolipids 84.2% higher.
limitations
Association does not establish a dietary cause, universal threshold or supplementation benefit.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A low measured amino-acid pool was associated with an abnormal lipid signature.
primary_references
Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 270–276
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human case-control metabolomics; serine 20.6% lower and deoxysphingolipids 84.2% higher. · source_derived_draft · unverified_draft
## l-serine-mac-tel-association A low measured amino-acid pool was associated with an abnormal lipid signature. Among 125 MacTel type 2 patients without pathogenic SPT variants and 94 controls, circulating serine was lower and deoxysphingolipids higher in the patient group. Model: Human case-control metabolomics; serine 20.6% lower and deoxysphingolipids 84.2% higher. Limitations: Association does not establish a dietary cause, universal threshold or supplementation benefit. Evidence access: Primary abstract Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
Complete structured claim and evidence
Experimentally lowering serine in mice increased retinal deoxysphingolipids and compromised visual function.
L-Serine → Retinal deoxysphingolipid accumulation in low-serine mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse low-serine model in the MacTel study.
limitations
Mouse manipulation is distinct from the observational human plasma comparison.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Reduced availability can change the products of lipid synthesis.
primary_references
Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 278–284
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse low-serine model in the MacTel study. · source_derived_draft · unverified_draft
## l-serine-mouse-low-serine-retina Reduced availability can change the products of lipid synthesis. Experimentally lowering serine in mice increased retinal deoxysphingolipids and compromised visual function. Model: Mouse low-serine model in the MacTel study. Limitations: Mouse manipulation is distinct from the observational human plasma comparison. Evidence access: Primary abstract Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
Complete structured claim and evidence
Deoxysphingolipid exposure caused photoreceptor-cell death in human retinal organoids, which was prevented by tested regulators of lipid metabolism.
1-Deoxysphingolipids → Photoreceptor survival in human retinal organoids source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human retinal organoid exposure experiment.
limitations
The result does not establish effective serine treatment for people with MacTel.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The abnormal lipid can itself damage cells in an experimental retinal model.
primary_references
Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 286–292
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human retinal organoid exposure experiment. · source_derived_draft · unverified_draft
## l-serine-organoid-lipid-toxicity The abnormal lipid can itself damage cells in an experimental retinal model. Deoxysphingolipid exposure caused photoreceptor-cell death in human retinal organoids, which was prevented by tested regulators of lipid metabolism. Model: Human retinal organoid exposure experiment. Limitations: The result does not establish effective serine treatment for people with MacTel. Evidence access: Primary abstract Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31509666/ · DOI 10.1056/NEJMoa1815111
Complete structured claim and evidence
In the randomized HSAN1 trial, oral L-serine reduced deoxysphinganine by 59% versus an 11% increase with placebo after one year.
L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
18 randomized adults; 16 completed; 400 mg/kg/day versus placebo for one year followed by open-label treatment.
limitations
High-dose disease-specific research regimen, not a general supplement recommendation.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Changing substrate supply changed the abnormal lipid product in this inherited disorder.
primary_references
Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30626650/ · DOI 10.1212/WNL.0000000000006811
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 294–300
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 18 randomized adults; 16 completed; 400 mg/kg/day versus placebo for one year followed by open-label treatment. · source_derived_draft · unverified_draft
## l-serine-hsan-trial-lipids Changing substrate supply changed the abnormal lipid product in this inherited disorder. In the randomized HSAN1 trial, oral L-serine reduced deoxysphinganine by 59% versus an 11% increase with placebo after one year. Model: 18 randomized adults; 16 completed; 400 mg/kg/day versus placebo for one year followed by open-label treatment. Limitations: High-dose disease-specific research regimen, not a general supplement recommendation. Evidence access: Primary abstract Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30626650/ · DOI 10.1212/WNL.0000000000006811
Complete structured claim and evidence
At one year, the L-serine group improved by 1.5 CMTNS units relative to placebo; the 95% confidence interval was -2.8 to -0.1 units.
L-Serine → HSAN1 trial neuropathy score source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same HSAN1 randomized trial as the lipid result; not independent participants.
limitations
Small rare-disease trial; benefit cannot be transferred to other neuropathies or ALS.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A small controlled trial also measured a clinical outcome.
primary_references
Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30626650/ · DOI 10.1212/WNL.0000000000006811
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 302–308
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same HSAN1 randomized trial as the lipid result; not independent participants. · source_derived_draft · unverified_draft
## l-serine-hsan-trial-neuropathy A small controlled trial also measured a clinical outcome. At one year, the L-serine group improved by 1.5 CMTNS units relative to placebo; the 95% confidence interval was -2.8 to -0.1 units. Model: Same HSAN1 randomized trial as the lipid result; not independent participants. Limitations: Small rare-disease trial; benefit cannot be transferred to other neuropathies or ALS. Evidence access: Primary abstract Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30626650/ · DOI 10.1212/WNL.0000000000006811
Complete structured claim and evidence
Four dominantly acting SPTLC1 variants in childhood-onset ALS families disrupted ORMDL-mediated feedback, increasing canonical sphingolipid synthesis.
Human serine palmitoyltransferase long-chain base subunit 1 → ORMDL restraint of human serine palmitoyltransferase source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human families and engineered cellular lipid-synthesis experiments.
limitations
This molecular subtype differs from HSAN1-associated substrate-switching variants.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Some variants remove the brake rather than change the preferred amino-acid substrate.
primary_references
Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34059824/ · DOI 10.1038/s41591-021-01346-1
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 310–316
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human families and engineered cellular lipid-synthesis experiments. · source_derived_draft · unverified_draft
## l-serine-als-spt-feedback Some variants remove the brake rather than change the preferred amino-acid substrate. Four dominantly acting SPTLC1 variants in childhood-onset ALS families disrupted ORMDL-mediated feedback, increasing canonical sphingolipid synthesis. Model: Human families and engineered cellular lipid-synthesis experiments. Limitations: This molecular subtype differs from HSAN1-associated substrate-switching variants. Evidence access: Primary abstract Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34059824/ · DOI 10.1038/s41591-021-01346-1
Complete structured claim and evidence
Adding excess serine further increased already elevated sphingolipid levels in mutant-SPTLC1 human iPSC-derived motor-neuron-like cells.
L-Serine → Sphingolipid excess in SPTLC1-ALS motor-neuron models source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full-text results section: serine supplementation and ALS-associated SPTLC1 variants
experimental_model
Primary full-text experiment in engineered human motor-neuron-like cells.
limitations
Measured biochemical worsening is distinct from a clinical outcome trial; this finding cannot be generalized to all ALS.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Extra substrate can feed an overactive pathway.
primary_references
Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34059824/ · DOI 10.1038/s41591-021-01346-1
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 318–324
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary full-text experiment in engineered human motor-neuron-like cells. · source_derived_draft · unverified_draft
## l-serine-als-serine-addition Extra substrate can feed an overactive pathway. Adding excess serine further increased already elevated sphingolipid levels in mutant-SPTLC1 human iPSC-derived motor-neuron-like cells. Model: Primary full-text experiment in engineered human motor-neuron-like cells. Limitations: Measured biochemical worsening is distinct from a clinical outcome trial; this finding cannot be generalized to all ALS. Evidence access: Primary full-text results section: serine supplementation and ALS-associated SPTLC1 variants Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34059824/ · DOI 10.1038/s41591-021-01346-1
Complete structured claim and evidence
Limiting serine in cells expressing SPTLC1-ALS variants increased deoxysphingolipids and shifted the lipid profile toward an HSAN1-like signature.
L-Serine → Substrate-dependent lipid signature in human SPTLC1-ALS models source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context.
limitations
Neither unrestricted supplementation nor restriction is shown to be a universal remedy.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Restricting substrate can trade one abnormal lipid pattern for another.
primary_references
SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35900868/ · DOI 10.1172/JCI161908
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 326–332
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context. · source_derived_draft · unverified_draft
## l-serine-spt-low-serine-switch Restricting substrate can trade one abnormal lipid pattern for another. Limiting serine in cells expressing SPTLC1-ALS variants increased deoxysphingolipids and shifted the lipid profile toward an HSAN1-like signature. Model: Cellular substrate manipulation, with a low-serine individual in an SPTLC1-ALS pedigree providing corroborating context. Limitations: Neither unrestricted supplementation nor restriction is shown to be a universal remedy. Evidence access: Primary abstract SPTLC1 variants associated with ALS produce distinct sphingolipid signatures through impaired interaction with ORMDL proteins. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35900868/ · DOI 10.1172/JCI161908
Complete structured claim and evidence
Two unrelated individuals with biallelic SLC1A4 variants had severe developmental delay, progressive microcephaly, seizures, spasticity and thin corpus callosum.
Human neutral amino acid exchanger ASCT1 / SLC1A4 → Neurodevelopmental disease associated with SLC1A4 variants source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human trio-exome analysis and structural prediction.
limitations
The proposed astrocyte-to-neuron transport mechanism was not directly measured in these two patients.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A transport defect can matter even when amino-acid synthesis is present.
primary_references
SLC1A4 mutations cause a novel disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26138499/ · DOI 10.1111/cge.12637
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 334–340
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human trio-exome analysis and structural prediction. · source_derived_draft · unverified_draft
## l-serine-asct1-genetic A transport defect can matter even when amino-acid synthesis is present. Two unrelated individuals with biallelic SLC1A4 variants had severe developmental delay, progressive microcephaly, seizures, spasticity and thin corpus callosum. Model: Human trio-exome analysis and structural prediction. Limitations: The proposed astrocyte-to-neuron transport mechanism was not directly measured in these two patients. Evidence access: Primary abstract SLC1A4 mutations cause a novel disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26138499/ · DOI 10.1111/cge.12637
Complete structured claim and evidence
Astrocytic Phgdh inhibition reduced newly synthesized L- and D-serine; neuronal serine-racemase deletion reduced D-serine synthesis to a similar extent.
Mouse phosphoglycerate dehydrogenase / Phgdh → New D-serine synthesis in mouse neurons source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse genetic and hippocampal experiments with synthesis measurements.
limitations
This does not establish exclusive cell-type localization under every developmental or disease condition.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Support cells can supply precursor while neurons perform the final conversion.
primary_references
The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 342–348
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic and hippocampal experiments with synthesis measurements. · source_derived_draft · unverified_draft
## l-serine-astrocyte-shuttle Support cells can supply precursor while neurons perform the final conversion. Astrocytic Phgdh inhibition reduced newly synthesized L- and D-serine; neuronal serine-racemase deletion reduced D-serine synthesis to a similar extent. Model: Mouse genetic and hippocampal experiments with synthesis measurements. Limitations: This does not establish exclusive cell-type localization under every developmental or disease condition. Evidence access: Primary abstract The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116
Complete structured claim and evidence
Enzymatic removal of extracellular L-serine impaired hippocampal long-term potentiation, supporting a role for an intercellular serine supply route.
L-Serine → Mouse hippocampal serine-shuttle-dependent plasticity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse hippocampal synaptic experiments.
limitations
L-serine supplies D-serine; this is not evidence that L-serine directly substitutes at the NMDAR coagonist site.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Removing extracellular precursor can disrupt a downstream signaling response.
primary_references
The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 350–356
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse hippocampal synaptic experiments. · source_derived_draft · unverified_draft
## l-serine-shuttle-ltp Removing extracellular precursor can disrupt a downstream signaling response. Enzymatic removal of extracellular L-serine impaired hippocampal long-term potentiation, supporting a role for an intercellular serine supply route. Model: Mouse hippocampal synaptic experiments. Limitations: L-serine supplies D-serine; this is not evidence that L-serine directly substitutes at the NMDAR coagonist site. Evidence access: Primary abstract The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116
Complete structured claim and evidence
Intracellular glycine tonically inhibited serine racemase in the study, while glycine exposure could transiently promote D-serine release through Asc-1.
Glycine → Mouse serine racemase / Srr source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Biochemical assays, primary cultures and mouse microdialysis; Asc-1 knockout abolished the release response.
limitations
Inhibition of synthesis and stimulation of release are distinct endpoints, not contradictory directions for one reaction.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The same neighboring amino acid can affect both production and release in different ways.
primary_references
The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 358–364
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Biochemical assays, primary cultures and mouse microdialysis; Asc-1 knockout abolished the release response. · source_derived_draft · unverified_draft
## l-serine-glycine-racemase The same neighboring amino acid can affect both production and release in different ways. Intracellular glycine tonically inhibited serine racemase in the study, while glycine exposure could transiently promote D-serine release through Asc-1. Model: Biochemical assays, primary cultures and mouse microdialysis; Asc-1 knockout abolished the release response. Limitations: Inhibition of synthesis and stimulation of release are distinct endpoints, not contradictory directions for one reaction. Evidence access: Primary abstract The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31548413/ · DOI 10.1073/pnas.1909458116
Complete structured claim and evidence
Human liver serine dehydratase uses PLP to convert L-serine to pyruvate and ammonia; its active holoenzyme was structurally characterized.
Human hepatic serine dehydratase / SDS → Pyruvate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure.
limitations
Enzyme capacity does not quantify its share of whole-body serine disposal.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Serine carbon can enter central metabolism through a B6-dependent breakdown step.
primary_references
Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15689518/ · DOI 10.1110/ps.041179105
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 366–372
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure. · source_derived_draft · unverified_draft
## l-serine-sds-catabolism Serine carbon can enter central metabolism through a B6-dependent breakdown step. Human liver serine dehydratase uses PLP to convert L-serine to pyruvate and ammonia; its active holoenzyme was structurally characterized. Model: Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure. Limitations: Enzyme capacity does not quantify its share of whole-body serine disposal. Evidence access: Primary abstract Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15689518/ · DOI 10.1110/ps.041179105
Complete structured claim and evidence
Human serine dehydratase-like protein had lower activity than the hepatic enzyme; structures and complementary mutations implicated active-site differences, including Gly72.
Human serine dehydratase-like protein / SDSL → Human hepatic serine dehydratase / SDS source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human enzymes, 2.8-angstrom SDSL structure and site-directed mutagenesis.
limitations
This is a comparison of enzyme constructs, not clinical evidence of a dietary shortage.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Related enzymes are not interchangeable just because they use the same substrate.
primary_references
A catalytic mechanism that explains a low catalytic activity of serine dehydratase like-1 from human cancer cells: crystal structure and site-directed mutagenesis studies. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18342636/ · DOI 10.1016/j.bbagen.2008.01.020
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 374–380
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzymes, 2.8-angstrom SDSL structure and site-directed mutagenesis. · source_derived_draft · unverified_draft
## l-serine-sdsl-distinction Related enzymes are not interchangeable just because they use the same substrate. Human serine dehydratase-like protein had lower activity than the hepatic enzyme; structures and complementary mutations implicated active-site differences, including Gly72. Model: Recombinant human enzymes, 2.8-angstrom SDSL structure and site-directed mutagenesis. Limitations: This is a comparison of enzyme constructs, not clinical evidence of a dietary shortage. Evidence access: Primary abstract A catalytic mechanism that explains a low catalytic activity of serine dehydratase like-1 from human cancer cells: crystal structure and site-directed mutagenesis studies. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18342636/ · DOI 10.1016/j.bbagen.2008.01.020
Complete structured claim and evidence
Human PSTK phosphorylates serine attached to tRNA Sec as part of the specialized selenocysteine synthesis pathway.
Human phosphoseryl-tRNA kinase / PSTK → Seryl-tRNA Sec source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified human PSTK with tRNA substrates; comparison with KTI12.
limitations
This is tRNA-bound serine chemistry, not direct conversion of free serine into free selenocysteine.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A serine molecule already loaded onto a tRNA is processed into a selenium-containing amino-acid precursor.
primary_references
Same but different - Molecular comparison of human KTI12 and PSTK. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33417976/ · DOI 10.1016/j.bbamcr.2020.118945
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 382–388
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human PSTK with tRNA substrates; comparison with KTI12. · source_derived_draft · unverified_draft
## l-serine-pstk-serine A serine molecule already loaded onto a tRNA is processed into a selenium-containing amino-acid precursor. Human PSTK phosphorylates serine attached to tRNA Sec as part of the specialized selenocysteine synthesis pathway. Model: Purified human PSTK with tRNA substrates; comparison with KTI12. Limitations: This is tRNA-bound serine chemistry, not direct conversion of free serine into free selenocysteine. Evidence access: Primary abstract Same but different - Molecular comparison of human KTI12 and PSTK. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33417976/ · DOI 10.1016/j.bbamcr.2020.118945
Complete structured claim and evidence
Human SepSecS structural and functional analysis supported correct positioning of tRNA-bound phosphoserine, but not free phosphoserine, for PLP-dependent selenocysteine formation.
SEPSECS / SepSecS → O-phosphoseryl-tRNA Sec source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human SepSecS–tRNA complex structure with enzyme assays.
limitations
Free phosphoserine and a phosphoserine residue on this specialized tRNA are not interchangeable substrates.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The carrier and the cofactor are part of the reaction, not optional packaging.
primary_references
The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19608919/ · DOI 10.1126/science.1173755
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 390–396
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SepSecS–tRNA complex structure with enzyme assays. · source_derived_draft · unverified_draft
## l-serine-sepsecs-substrate The carrier and the cofactor are part of the reaction, not optional packaging. Human SepSecS structural and functional analysis supported correct positioning of tRNA-bound phosphoserine, but not free phosphoserine, for PLP-dependent selenocysteine formation. Model: Human SepSecS–tRNA complex structure with enzyme assays. Limitations: Free phosphoserine and a phosphoserine residue on this specialized tRNA are not interchangeable substrates. Evidence access: Primary abstract The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19608919/ · DOI 10.1126/science.1173755
Complete structured claim and evidence
Purified BMAA was not a substrate for human seryl-tRNA synthetase in the study; human alanyl-tRNA synthetase instead activated it and formed BMAA-tRNA Ala.
Human cytosolic seryl-tRNA synthetase / SARS1 → Beta-N-methylamino-L-alanine / BMAA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified-substrate amino-acid activation and tRNA-charging assays.
limitations
Aminoacylation is not direct proof of the frequency of proteome misincorporation in humans.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Chemical similarity to serine does not establish entry through the serine-loading enzyme.
primary_references
The mechanism of β-N-methylamino-l-alanine inhibition of tRNA aminoacylation and its impact on misincorporation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31862734/ · DOI 10.1074/jbc.RA119.011714
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 398–404
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-substrate amino-acid activation and tRNA-charging assays. · source_derived_draft · unverified_draft
## l-serine-serrs-bmaa-boundary Chemical similarity to serine does not establish entry through the serine-loading enzyme. Purified BMAA was not a substrate for human seryl-tRNA synthetase in the study; human alanyl-tRNA synthetase instead activated it and formed BMAA-tRNA Ala. Model: Purified-substrate amino-acid activation and tRNA-charging assays. Limitations: Aminoacylation is not direct proof of the frequency of proteome misincorporation in humans. Evidence access: Primary abstract The mechanism of β-N-methylamino-l-alanine inhibition of tRNA aminoacylation and its impact on misincorporation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31862734/ · DOI 10.1074/jbc.RA119.011714
Complete structured claim and evidence
Human serine racemase catalyzes the PLP-dependent formation of D-serine from L-serine; replacing Ser84 with alanine shifted its behavior toward serine dehydratase activity.
Human serine racemase / SRR → D-Serine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human serine racemase and serine dehydratase mutants with functional comparisons.
limitations
Engineered reaction switching does not mean the native enzymes have identical functions.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
One enzyme creates the D-form used in a distinct signaling pathway.
primary_references
Modulating the function of human serine racemase and human serine dehydratase by protein engineering. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23112234/ · DOI 10.1093/protein/gzs078
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 406–412
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human serine racemase and serine dehydratase mutants with functional comparisons. · source_derived_draft · unverified_draft
## l-serine-srr-racemization One enzyme creates the D-form used in a distinct signaling pathway. Human serine racemase catalyzes the PLP-dependent formation of D-serine from L-serine; replacing Ser84 with alanine shifted its behavior toward serine dehydratase activity. Model: Recombinant human serine racemase and serine dehydratase mutants with functional comparisons. Limitations: Engineered reaction switching does not mean the native enzymes have identical functions. Evidence access: Primary abstract Modulating the function of human serine racemase and human serine dehydratase by protein engineering. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23112234/ · DOI 10.1093/protein/gzs078
Complete structured claim and evidence
Purified human PSS2 converted phosphatidylethanolamine, but not phosphatidylcholine, into phosphatidylserine; added phosphatidylserine inhibited purified PSS2.
Human phosphatidylserine synthase 2 / PTDSS2 → Phosphatidylserine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified epitope-tagged human PSS1/PSS2 substrate and feedback assays.
limitations
In this preparation PSS1 used both PC and PE and was not inhibited by added PS; purified-enzyme feedback cannot be assumed identical across preparations or intact cells.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A second enzyme uses a different membrane-lipid starting material.
primary_references
Purification and characterization of human phosphatidylserine synthases 1 and 2. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19014349/ · DOI 10.1042/BJ20081597
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 414–420
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified epitope-tagged human PSS1/PSS2 substrate and feedback assays. · source_derived_draft · unverified_draft
## l-serine-pss2-exchange A second enzyme uses a different membrane-lipid starting material. Purified human PSS2 converted phosphatidylethanolamine, but not phosphatidylcholine, into phosphatidylserine; added phosphatidylserine inhibited purified PSS2. Model: Purified epitope-tagged human PSS1/PSS2 substrate and feedback assays. Limitations: In this preparation PSS1 used both PC and PE and was not inhibited by added PS; purified-enzyme feedback cannot be assumed identical across preparations or intact cells. Evidence access: Primary abstract Purification and characterization of human phosphatidylserine synthases 1 and 2. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19014349/ · DOI 10.1042/BJ20081597
Complete structured claim and evidence
Human PISD converts phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane; patient fibroblasts with PISD variants showed reduced conversion.
Human phosphatidylserine decarboxylase / PISD → Phosphatidylethanolamine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human family genetics and fibroblast lipid-conversion measurements.
limitations
This pathway uses membrane-bound phosphatidylserine, not free serine as the direct PISD substrate.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A serine-derived lipid feeds another lipid needed inside mitochondria.
primary_references
PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30858161/ · DOI 10.26508/lsa.201900353
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 422–428
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human family genetics and fibroblast lipid-conversion measurements. · source_derived_draft · unverified_draft
## l-serine-pisd-decarboxylation A serine-derived lipid feeds another lipid needed inside mitochondria. Human PISD converts phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane; patient fibroblasts with PISD variants showed reduced conversion. Model: Human family genetics and fibroblast lipid-conversion measurements. Limitations: This pathway uses membrane-bound phosphatidylserine, not free serine as the direct PISD substrate. Evidence access: Primary abstract PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30858161/ · DOI 10.26508/lsa.201900353
Complete structured claim and evidence
PISD patient fibroblasts had fragmented mitochondria, enlarged lysosomes and reduced maximal oxygen consumption; one variant impaired the enzyme autocatalytic processing required for activity.
Human phosphatidylserine decarboxylase / PISD → Mitochondrial function in PISD patient fibroblasts source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Two affected sisters, patient fibroblasts and functional variant characterization.
limitations
The other allele produced an alternative splice product; different molecular defects remain distinct.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
A downstream processing defect can persist despite precursor availability.
primary_references
PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30858161/ · DOI 10.26508/lsa.201900353
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 430–436
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two affected sisters, patient fibroblasts and functional variant characterization. · source_derived_draft · unverified_draft
## l-serine-pisd-failure A downstream processing defect can persist despite precursor availability. PISD patient fibroblasts had fragmented mitochondria, enlarged lysosomes and reduced maximal oxygen consumption; one variant impaired the enzyme autocatalytic processing required for activity. Model: Two affected sisters, patient fibroblasts and functional variant characterization. Limitations: The other allele produced an alternative splice product; different molecular defects remain distinct. Evidence access: Primary abstract PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30858161/ · DOI 10.26508/lsa.201900353
Complete structured claim and evidence
Lyso-PE treatment and genetic complementation restored mitochondrial and lysosomal morphology in PISD patient fibroblasts.
Lysophosphatidylethanolamine → Organelle morphology in PISD patient fibroblasts source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human patient fibroblast rescue experiments.
limitations
This is not evidence that oral serine or phosphatidylserine corrects PISD disease.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Supplying a downstream lipid can bypass a specific defect in culture.
primary_references
PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30858161/ · DOI 10.26508/lsa.201900353
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 438–444
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human patient fibroblast rescue experiments. · source_derived_draft · unverified_draft
## l-serine-pisd-lipid-rescue Supplying a downstream lipid can bypass a specific defect in culture. Lyso-PE treatment and genetic complementation restored mitochondrial and lysosomal morphology in PISD patient fibroblasts. Model: Human patient fibroblast rescue experiments. Limitations: This is not evidence that oral serine or phosphatidylserine corrects PISD disease. Evidence access: Primary abstract PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30858161/ · DOI 10.26508/lsa.201900353
Complete structured claim and evidence
Human cytosolic SerRS attached L-serine to tRNA Ser and showed only a modest preference for it over tRNA Sec in the tested binding and serylation experiments.
Human cytosolic seryl-tRNA synthetase / SARS1 → Human cytosolic tRNA Ser source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human SerRS with two tRNA species and ten mutant/chimeric constructs.
limitations
Carrier recognition is distinct from ordinary amino-acid transport or downstream protein phosphorylation.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
Serine must be attached to a tRNA before it can enter a growing protein.
primary_references
Insights into substrate promiscuity of human seryl-tRNA synthetase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28808125/ · DOI 10.1261/rna.061069.117
L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 446–452
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SerRS with two tRNA species and ten mutant/chimeric constructs. · source_derived_draft · unverified_draft
## l-serine-serrs-protein-route Serine must be attached to a tRNA before it can enter a growing protein. Human cytosolic SerRS attached L-serine to tRNA Ser and showed only a modest preference for it over tRNA Sec in the tested binding and serylation experiments. Model: Human SerRS with two tRNA species and ten mutant/chimeric constructs. Limitations: Carrier recognition is distinct from ordinary amino-acid transport or downstream protein phosphorylation. Evidence access: Primary abstract Insights into substrate promiscuity of human seryl-tRNA synthetase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28808125/ · DOI 10.1261/rna.061069.117
Complete structured claim and evidence
Human SerRS also attached L-serine to tRNA Sec, initiating the specialized pathway that later converts its attached amino acid into selenocysteine.
Human cytosolic seryl-tRNA synthetase / SARS1 → Seryl-tRNA Sec source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cytosolic SerRS substrate-recognition and aminoacylation experiments.
limitations
Serylation does not itself add selenium; PSTK and SEPSECS act in later steps.
nutrient_topic
L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
plain_language
The same loading enzyme feeds both ordinary protein synthesis and selenium-dependent decoding.
primary_references
Insights into substrate promiscuity of human seryl-tRNA synthetase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28808125/ · DOI 10.1261/rna.061069.117
L-Serine: synthesis, one-carbon metabolism, lipids 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 · Human cytosolic SerRS substrate-recognition and aminoacylation experiments. · source_derived_draft · unverified_draft
## l-serine-serrs-selenium-route The same loading enzyme feeds both ordinary protein synthesis and selenium-dependent decoding. Human SerRS also attached L-serine to tRNA Sec, initiating the specialized pathway that later converts its attached amino acid into selenocysteine. Model: Human cytosolic SerRS substrate-recognition and aminoacylation experiments. Limitations: Serylation does not itself add selenium; PSTK and SEPSECS act in later steps. Evidence access: Primary abstract Insights into substrate promiscuity of human seryl-tRNA synthetase. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28808125/ · DOI 10.1261/rna.061069.117
Complete structured claim and evidence
Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction.
Human cystathionine gamma-lyase / CTH → Cystathionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes.
experimental_model
Purified human CTH apo/holo crystal structures and assays
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This step releases cysteine for downstream metabolism.
primary_references
[b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 554–564
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CTH apo/holo crystal structures and assays · source_derived_draft · unverified_draft
### b6-met-cth-cleavage Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This step releases cysteine for downstream metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human CTH apo/holo crystal structures and assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes. [b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
Complete structured claim and evidence
PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine.
Human cystathionine beta-synthase / CBS → Cystathionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Methionine-derived sulfur enters cysteine synthesis.
experimental_model
Recombinant truncated human CBS crystallography
limitations
Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency.
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 channels homocysteine into transsulfuration.
primary_references
[b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 517–527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant truncated human CBS crystallography · source_derived_draft · unverified_draft
### b6-met-cbs-condensation PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine. 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 channels homocysteine into transsulfuration. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant truncated human CBS crystallography limitations: Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency. cross_nutrient: Methionine-derived sulfur enters cysteine synthesis. [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
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
PLP-dependent human SPT condenses serine and palmitoyl-CoA into 3-ketosphinganine; the product-bound structure locates its headgroup and acyl chain.
Human SPTLC1-SPTLC2-SPTSSA complex → 3-Ketosphinganine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent use of the amino acid serine and a fatty-acyl-CoA substrate.
experimental_model
Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays
exposure
Product-bound cryo-EM and functional enzyme assays.
limitations
Does not show that B6 supplementation repairs myelin.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
B6 supports entry into sphingolipid synthesis.
primary_references
[wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1120–1131
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays · source_derived_draft · unverified_draft
### b6-neuro-spt-sphingolipid-entry PLP-dependent human SPT condenses serine and palmitoyl-CoA into 3-ketosphinganine; the product-bound structure locates its headgroup and acyl chain. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 supports entry into sphingolipid synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SPT complexes; cryo-EM and cell/microsome activity assays limitations: Does not show that B6 supplementation repairs myelin. exposure: Product-bound cryo-EM and functional enzyme assays. cross_nutrient: B6-dependent use of the amino acid serine and a fatty-acyl-CoA substrate. [wang-2021-spt] Structural insights into the regulation of human serine palmitoyltransferase complexes (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC9812531/ DOI: 10.1038/s41594-020-00551-9
Complete structured claim and evidence
In nutrient-replete HEK293T and HCT116 cells, isotope tracing showed net SHMT1 flux toward serine synthesis.
SHMT1 → L-Serine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Links existing B6-dependent SHMT chemistry to folate flux direction.
experimental_model
Stable-isotope tracing
exposure
Assay conditions described in the linked primary study.
limitations
Not a universal direction across tissues or nutrition states.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
SHMT1 can consume one-carbon units instead of producing them.
primary_references
[ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016
tissue_or_cell_type
HEK293T and HCT116 cells
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 923–934
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracing · source_derived_draft · unverified_draft
### shmt1-reverse-flux-replete In nutrient-replete HEK293T and HCT116 cells, isotope tracing showed net SHMT1 flux toward serine synthesis. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: SHMT1 can consume one-carbon units instead of producing them. organism: Homo sapiens tissue_or_cell_type: HEK293T and HCT116 cells experimental_model: Stable-isotope tracing limitations: Not a universal direction across tissues or nutrition states. exposure: Assay conditions described in the linked primary study. cross_nutrient: Links existing B6-dependent SHMT chemistry to folate flux direction. [ducker-2016] Reversal of Cytosolic One-Carbon Flux Compensates for Loss of the Mitochondrial Folate Pathway (2016). https://pubmed.ncbi.nlm.nih.gov/27211901/ DOI: 10.1016/j.cmet.2016.04.016
Complete structured claim and evidence
Tested cancer cells and IMR90 fibroblasts released most serine-derived one-carbon units as formate rather than retaining them for biosynthesis.
L-Serine → Cellular formate release source_derived_draftungraded
Experimental context and source evidence
experimental_model
Stable-isotope and exchange-rate measurements
exposure
Assay conditions described in the linked primary study.
limitations
Fractions depend on culture conditions.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Cells can make more one-carbon units than they use locally.
primary_references
[meiser-2016] Serine one-carbon catabolism with formate overflow (2016). https://pubmed.ncbi.nlm.nih.gov/27819051/ DOI: 10.1126/sciadv.1601273
tissue_or_cell_type
Cultured cancer cells and lung fibroblasts
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1206–1216
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope and exchange-rate measurements · source_derived_draft · unverified_draft
### serine-formate-overflow Tested cancer cells and IMR90 fibroblasts released most serine-derived one-carbon units as formate rather than retaining them for biosynthesis. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells can make more one-carbon units than they use locally. organism: Homo sapiens tissue_or_cell_type: Cultured cancer cells and lung fibroblasts experimental_model: Stable-isotope and exchange-rate measurements limitations: Fractions depend on culture conditions. exposure: Assay conditions described in the linked primary study. [meiser-2016] Serine one-carbon catabolism with formate overflow (2016). https://pubmed.ncbi.nlm.nih.gov/27819051/ DOI: 10.1126/sciadv.1601273
Complete structured claim and evidence
Isotope tracing supported the beta-carbon of serine entering the methylene group of mitochondrial taurine-modified uridine through 5,10-methylene-THF.
5,10-Methylenetetrahydrofolate → Mitochondrial tRNA 5-taurinomethyluridine / tau-m5U34 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, Figure 1 and metabolic-labeling experiments
experimental_model
Human HeLa metabolic labeling plus biochemical reconstitution.
limitations
A folate connection is not evidence for a benefit from folic acid supplementation in replete people.
nutrient_topic
Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine
plain_language
Folate chemistry contributes part of the RNA mark; taurine supplies a different part.
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
Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 209–215
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HeLa metabolic labeling plus biochemical reconstitution. · source_derived_draft · unverified_draft
## taurine-folate-carbon-donor Folate chemistry contributes part of the RNA mark; taurine supplies a different part. Isotope tracing supported the beta-carbon of serine entering the methylene group of mitochondrial taurine-modified uridine through 5,10-methylene-THF. Model: Human HeLa metabolic labeling plus biochemical reconstitution. Limitations: A folate connection is not evidence for a benefit from folic acid supplementation in replete people. Evidence access: Primary full text, Figure 1 and metabolic-labeling experiments 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
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
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
The 1.89-angstrom human serine-racemase holoenzyme structure included its bound pyridoxal-phosphate cofactor.
PLP → Human serine racemase / SRR source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified human SRR crystal structure.
limitations
Structural cofactor binding does not establish dietary B6 control of human D-aspartate or an effective supplementation threshold.
nutrient_topic
D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
plain_language
Vitamin B6-derived PLP is part of the shared racemase machinery.
primary_references
Conformational flexibility within the small domain of human serine racemase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32039887/ · DOI 10.1107/S2053230X20001193
D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 56–62
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human SRR crystal structure. · source_derived_draft · unverified_draft
## d-aspartate-srr-plp Vitamin B6-derived PLP is part of the shared racemase machinery. The 1.89-angstrom human serine-racemase holoenzyme structure included its bound pyridoxal-phosphate cofactor. Model: Purified human SRR crystal structure. Limitations: Structural cofactor binding does not establish dietary B6 control of human D-aspartate or an effective supplementation threshold. Evidence access: Primary abstract Conformational flexibility within the small domain of human serine racemase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32039887/ · DOI 10.1107/S2053230X20001193
Complete structured claim and evidence
Mg2+ and ATP increased recombinant serine-racemase serine racemization and pyruvate production by approximately five- to ten-fold in the study assay.
Serine-racemase cofactor assay, construct species unresolved here → Magnesium/ATP stimulation of serine-racemase activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant enzyme and cell-extract experiments; construct species not resolved in accessed abstract.
limitations
This is a shared-machinery connection, not a demonstrated magnesium effect on D-aspartate flux.
nutrient_topic
D-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · D-Aspartate
plain_language
Mineral and energy cofactors affect this enzyme, but the measured substrate was serine.
primary_references
Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12393813/ · DOI 10.1073/pnas.222421299
D-Aspartate: synthesis, clearance, neural and endocrine mechanisms (2026-09-19) · lines 64–70
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant enzyme and cell-extract experiments; construct species not resolved in accessed abstract. · source_derived_draft · unverified_draft
## d-aspartate-srr-mg-atp Mineral and energy cofactors affect this enzyme, but the measured substrate was serine. Mg2+ and ATP increased recombinant serine-racemase serine racemization and pyruvate production by approximately five- to ten-fold in the study assay. Model: Recombinant enzyme and cell-extract experiments; construct species not resolved in accessed abstract. Limitations: This is a shared-machinery connection, not a demonstrated magnesium effect on D-aspartate flux. Evidence access: Primary abstract Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12393813/ · DOI 10.1073/pnas.222421299
Complete structured claim and evidence
A 10% serine-enriched diet reduced deoxysphingolipids and improved selected motor and sensory outcomes in C133W SPTLC1 transgenic mice.
L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
HSAN1 transgenic mouse dietary intervention.
limitations
Mouse neurological outcomes do not establish human clinical benefit.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Restoring the competing normal substrate changed the abnormal lipid output.
primary_references
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 440–446
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HSAN1 transgenic mouse dietary intervention. · source_derived_draft · unverified_draft
## alanine-spt-serine-rescue Restoring the competing normal substrate changed the abnormal lipid output. A 10% serine-enriched diet reduced deoxysphingolipids and improved selected motor and sensory outcomes in C133W SPTLC1 transgenic mice. Model: HSAN1 transgenic mouse dietary intervention. Limitations: Mouse neurological outcomes do not establish human clinical benefit. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
Complete structured claim and evidence
A pilot study in 14 HSAN1 patients found reduced deoxysphingolipid levels during oral serine supplementation.
L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Small human HSAN1 serine-supplementation pilot.
limitations
Biomarker lowering alone does not establish neurological recovery, and the intervention was serine rather than alanine.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The human pilot measured a biochemical response.
primary_references
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 448–454
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small human HSAN1 serine-supplementation pilot. · source_derived_draft · unverified_draft
## alanine-spt-human-serine The human pilot measured a biochemical response. A pilot study in 14 HSAN1 patients found reduced deoxysphingolipid levels during oral serine supplementation. Model: Small human HSAN1 serine-supplementation pilot. Limitations: Biomarker lowering alone does not establish neurological recovery, and the intervention was serine rather than alanine. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
Complete structured claim and evidence
Serine/glycine restriction increased alanine-derived deoxysphingolipid synthesis in the tested colorectal cancer models and constrained growth.
Serine/glycine restriction in human colorectal cancer models → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts.
limitations
Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting.
primary_references
Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 456–462
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. · source_derived_draft · unverified_draft
## alanine-serine-restriction-lipids The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting. Serine/glycine restriction increased alanine-derived deoxysphingolipid synthesis in the tested colorectal cancer models and constrained growth. Model: Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. Limitations: Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine. Evidence access: Primary full text Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
Complete structured claim and evidence
SEPSECS uses selenium from the donor to finish the tRNA-bound amino acid.
PLP-dependent SEPSECS converts phosphoseryl-tRNA Sec to Sec-tRNA through phosphate elimination and selenium donation from selenophosphate, not incorporation of intact selenophosphate.
SEPSECS / SepSecS → Sec-tRNA[Ser]Sec source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
Purified enzyme/tRNA
experimental_model
Human enzyme/tRNA crystallography and biochemical assays
limitations
Not a measurement of dietary intake effects.
organism
Homo sapiens
Selenium: literature corrections and mechanism additions · lines 1154–1164
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Human enzyme/tRNA crystallography and biochemical assays · secondary_verified · secondary_verified
## sepsecs-chemistry SEPSECS uses selenium from the donor to finish the tRNA-bound amino acid. PLP-dependent SEPSECS converts phosphoseryl-tRNA Sec to Sec-tRNA through phosphate elimination and selenium donation from selenophosphate, not incorporation of intact selenophosphate. Organism: Homo sapiens Cell type: Purified enzyme/tRNA Experimental model: Human enzyme/tRNA crystallography and biochemical assays Limitations: Not a measurement of dietary intake effects. Primary reference: [The human SepSecS–tRNASec complex reveals mechanism of selenocysteine formation](https://pubmed.ncbi.nlm.nih.gov/19608919/)
Complete structured claim and evidence
Proline supported de novo serine synthesis and reductive carboxylation in cultured human RPE.
L-Proline → De novo serine synthesis in human RPE source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Primary human RPE culture and isotope tracing.
limitations
This is not a direct one-step conversion or a clinical serine-repletion trial.
nutrient_topic
L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
plain_language
Using one amino acid can support production of another.
primary_references
Proline mediates metabolic communication between retinal pigment epithelial cells and the retina. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31110046/ · DOI 10.1074/jbc.RA119.007983
L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 310–316
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary human RPE culture and isotope tracing. · source_derived_draft · unverified_draft
## l-proline-rpe-serine Using one amino acid can support production of another. Proline supported de novo serine synthesis and reductive carboxylation in cultured human RPE. Model: Primary human RPE culture and isotope tracing. Limitations: This is not a direct one-step conversion or a clinical serine-repletion trial. Evidence access: Primary abstract Proline mediates metabolic communication between retinal pigment epithelial cells and the retina. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31110046/ · DOI 10.1074/jbc.RA119.007983
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.

A synthesis defect can create an internal shortage

Condition: machinery_impairment · Inherited or engineered impairment of PHGDH, PSAT1 or PSPH.

Normal role: Cells synthesize or import serine and allocate it to protein, lipid, one-carbon and signaling pathways through distinct enzymes.

Recorded consequence: Enzyme dysfunction or low serine; clinical responses vary by outcome and timing.