L-Threonine

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full-text Figure 3 results excerpt

experimental_model

Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation.

limitations

Not a human supplementation trial or evidence that serum MMA exclusively reports B12 status.

nutrient_topic

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

plain_language

More substrate affected a blocked metabolic setting differently from controls.

primary_references

An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 410–416

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation. · source_derived_draft · unverified_draft

## l-threonine-acsf3-threonine-addition More substrate affected a blocked metabolic setting differently from controls. Threonine in drinking water increased serum methylmalonic acid in Acsf3-null mice on a ketogenic diet, but not significantly in controls. Model: Mouse genotype-by-diet experiment; ketogenic diet with amino-acid supplementation. Limitations: Not a human supplementation trial or evidence that serum MMA exclusively reports B12 status. Evidence access: Primary full-text Figure 3 results excerpt An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse dietary essential-amino-acid restriction and FGF21-dependency experiments.

limitations

Mouse metabolic responses are not evidence that restriction is appropriate for humans or developing animals.

nutrient_topic

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

plain_language

A liver hormone mediates part of the organism-level response to restricted supply.

primary_references

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32518324/ · DOI 10.1038/s41467-020-16568-z

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 346–352

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse dietary essential-amino-acid restriction and FGF21-dependency experiments. · source_derived_draft · unverified_draft

## l-threonine-fgf21-restriction A liver hormone mediates part of the organism-level response to restricted supply. Dietary threonine restriction produced systemic metabolic remodeling in mice that required liver-derived FGF21. Model: Mouse dietary essential-amino-acid restriction and FGF21-dependency experiments. Limitations: Mouse metabolic responses are not evidence that restriction is appropriate for humans or developing animals. Evidence access: Primary abstract Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32518324/ · DOI 10.1038/s41467-020-16568-z

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Two-day-old piglets; intragastric adequate versus deficient diets.

limitations

Acidic mucin subtypes decreased in small intestine but increased in colon; these different sites must not be collapsed into one uniform response.

nutrient_topic

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

plain_language

A severe shortfall changed both mucus quantity and its distribution.

primary_references

Adequate oral threonine is critical for mucin production and gut function in neonatal piglets. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234895/ · DOI 10.1152/ajpgi.00221.2006

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 218–224

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two-day-old piglets; intragastric adequate versus deficient diets. · source_derived_draft · unverified_draft

## l-threonine-gut-deficiency-mucin A severe shortfall changed both mucus quantity and its distribution. Feeding neonatal piglets 0.1 rather than 0.6 g threonine/kg/day for eight days reduced colonic mucosal mass and mucin content and altered acidic mucin-producing goblet cells. Model: Two-day-old piglets; intragastric adequate versus deficient diets. Limitations: Acidic mucin subtypes decreased in small intestine but increased in colon; these different sites must not be collapsed into one uniform response. Evidence access: Primary abstract Adequate oral threonine is critical for mucin production and gut function in neonatal piglets. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234895/ · DOI 10.1152/ajpgi.00221.2006

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Same eight-day piglet intervention, not an independent cohort.

limitations

The experiment did not establish a human threshold for threonine-limited protein retention.

nutrient_topic

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

plain_language

Shortage of one amino acid can make other dietary nitrogen less efficiently retained.

primary_references

Adequate oral threonine is critical for mucin production and gut function in neonatal piglets. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234895/ · DOI 10.1152/ajpgi.00221.2006

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same eight-day piglet intervention, not an independent cohort. · source_derived_draft · unverified_draft

## l-threonine-gut-deficiency-nitrogen Shortage of one amino acid can make other dietary nitrogen less efficiently retained. The threonine-deficient piglets excreted more nitrogen and had higher plasma urea than adequate groups. Model: Same eight-day piglet intervention, not an independent cohort. Limitations: The experiment did not establish a human threshold for threonine-limited protein retention. Evidence access: Primary abstract Adequate oral threonine is critical for mucin production and gut function in neonatal piglets. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234895/ · DOI 10.1152/ajpgi.00221.2006

evidence_access

Primary abstract

experimental_model

Six pigs; isolated loops perfused for 120 minutes with an amino-acid mixture and labeled phenylalanine incorporation.

limitations

An acute local dose response is distinct from chronic whole-diet excess.

nutrient_topic

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

plain_language

The local amino-acid supply can change how quickly mucus protein is made.

primary_references

Luminal threonine concentration acutely affects intestinal mucosal protein and mucin synthesis in piglets. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18567751/ · DOI 10.1093/jn/138.7.1298

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 210–216

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Six pigs; isolated loops perfused for 120 minutes with an amino-acid mixture and labeled phenylalanine incorporation. · source_derived_draft · unverified_draft

## l-threonine-gut-local-synthesis The local amino-acid supply can change how quickly mucus protein is made. Increasing luminal threonine across 0, 21 and 56 mg/g total amino acids raised measured mucin synthesis in perfused intestinal loops. Model: Six pigs; isolated loops perfused for 120 minutes with an amino-acid mixture and labeled phenylalanine incorporation. Limitations: An acute local dose response is distinct from chronic whole-diet excess. Evidence access: Primary abstract Luminal threonine concentration acutely affects intestinal mucosal protein and mucin synthesis in piglets. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18567751/ · DOI 10.1093/jn/138.7.1298

evidence_access

Primary abstract

experimental_model

Four groups of eight pigs; 0.37%, 0.74%, 0.89% or 1.11% true ileal digestible threonine.

limitations

Pig diet percentages do not establish human doses. Different duration, preparation and endpoint explain why this need not oppose the acute loop experiment.

nutrient_topic

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

plain_language

More was not always better in a chronic feeding experiment.

primary_references

Optimal dietary true ileal digestible threonine for supporting the mucosal barrier in small intestine of weanling pigs. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20335627/ · DOI 10.3945/jn.109.118497

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 242–248

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four groups of eight pigs; 0.37%, 0.74%, 0.89% or 1.11% true ileal digestible threonine. · source_derived_draft · unverified_draft

## l-threonine-gut-nonlinearity More was not always better in a chronic feeding experiment. In weanling pigs, both 0.37% and 1.11% dietary digestible threonine reduced duodenal mucin and MUC2 expression relative to 0.89% during fourteen-day feeding. Model: Four groups of eight pigs; 0.37%, 0.74%, 0.89% or 1.11% true ileal digestible threonine. Limitations: Pig diet percentages do not establish human doses. Different duration, preparation and endpoint explain why this need not oppose the acute loop experiment. Evidence access: Primary abstract Optimal dietary true ileal digestible threonine for supporting the mucosal barrier in small intestine of weanling pigs. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20335627/ · DOI 10.3945/jn.109.118497

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Parenteral add-back during otherwise intragastric piglet feeding.

limitations

This is not an oral supplement trial; the same animals contribute several outcomes.

nutrient_topic

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

plain_language

Circulating supply compensated for much, but not every feature, of low luminal supply.

primary_references

Adequate oral threonine is critical for mucin production and gut function in neonatal piglets. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234895/ · DOI 10.1152/ajpgi.00221.2006

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 234–240

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Parenteral add-back during otherwise intragastric piglet feeding. · source_derived_draft · unverified_draft

## l-threonine-gut-parenteral-rescue Circulating supply compensated for much, but not every feature, of low luminal supply. Adding 0.5 g/kg/day intravenous threonine to the 0.1 g/kg/day oral supply maintained most measured outcomes, but colonic goblet-cell and mucin differences remained. Model: Parenteral add-back during otherwise intragastric piglet feeding. Limitations: This is not an oral supplement trial; the same animals contribute several outcomes. Evidence access: Primary abstract Adequate oral threonine is critical for mucin production and gut function in neonatal piglets. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17234895/ · DOI 10.1152/ajpgi.00221.2006

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

Detecting carbon transfer does not identify the enzyme responsible.

primary_references

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

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 290–296

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four-hour labeled-threonine/glycine infusions under control and high-threonine diets. · source_derived_draft · unverified_draft

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

evidence_access

Primary abstract

experimental_model

Same six men; control intake 50 versus 126 micromol/kg/hour in the two high-intake conditions.

limitations

Short controlled feeding/tracer study; not a long-term benefit or safety threshold.

nutrient_topic

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

plain_language

Extra intake can increase disposal rather than being retained unchanged.

primary_references

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

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 298–304

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same six men; control intake 50 versus 126 micromol/kg/hour in the two high-intake conditions. · source_derived_draft · unverified_draft

## l-threonine-human-oxidation-response Extra intake can increase disposal rather than being retained unchanged. High threonine intake supplied either as free amino acid or protein increased measured threonine oxidation to CO2 approximately threefold. Model: Same six men; control intake 50 versus 126 micromol/kg/hour in the two high-intake conditions. Limitations: Short controlled feeding/tracer study; not a long-term benefit or safety threshold. Evidence access: Primary abstract Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10780944/ · DOI 10.1152/ajpendo.2000.278.5.E877

evidence_access

Primary abstract

experimental_model

18 piglets, normal or protein-restricted isocaloric feeding; stable-isotope tracing after seven hours of enteral feeding.

limitations

Reported 91% versus 85% dietary utilization is specific to this model and feeding interval, not a human universal fraction.

nutrient_topic

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

plain_language

The gut uses much of the incoming amino acid before it reaches other tissues.

primary_references

Threonine utilization is high in the intestine of piglets. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795432/ · DOI 10.1093/jn/135.4.765

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 202–208

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 18 piglets, normal or protein-restricted isocaloric feeding; stable-isotope tracing after seven hours of enteral feeding. · source_derived_draft · unverified_draft

## l-threonine-intestinal-allocation The gut uses much of the incoming amino acid before it reaches other tissues. Piglet portal-drained viscera used a large fraction of dietary threonine, mainly through incorporation into mucosal proteins; dietary supply was preferentially used over systemic supply under normal-protein feeding. Model: 18 piglets, normal or protein-restricted isocaloric feeding; stable-isotope tracing after seven hours of enteral feeding. Limitations: Reported 91% versus 85% dietary utilization is specific to this model and feeding interval, not a human universal fraction. Evidence access: Primary abstract Threonine utilization is high in the intestine of piglets. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15795432/ · DOI 10.1093/jn/135.4.765

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Engineered mouse hepatocyte threonine synthesis during dietary restriction.

limitations

This experimentally installed pathway is not a normal mammalian threonine-synthesis route.

nutrient_topic

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

plain_language

Restoring supply in one organ changed a whole-body nutritional signal.

primary_references

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32518324/ · DOI 10.1038/s41467-020-16568-z

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 354–360

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Engineered mouse hepatocyte threonine synthesis during dietary restriction. · source_derived_draft · unverified_draft

## l-threonine-liver-supply-rescue Restoring supply in one organ changed a whole-body nutritional signal. Engineering threonine biosynthetic capacity selectively in hepatocytes reversed the systemic response to dietary threonine restriction. Model: Engineered mouse hepatocyte threonine synthesis during dietary restriction. Limitations: This experimentally installed pathway is not a normal mammalian threonine-synthesis route. Evidence access: Primary abstract Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32518324/ · DOI 10.1038/s41467-020-16568-z

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 330–336

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse stem-cell isotope tracing and culture-medium withdrawal. · source_derived_draft · unverified_draft

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

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

trigger_kind

biomarker_context Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 418–424

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 61 genetically confirmed patients versus reference data from 274 controls; stereoselective serine analysis in a smaller subset. · source_derived_draft · unverified_draft

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

evidence_access

Primary full-text Table 5, publisher PDF

experimental_model

Table 5: three observations per transporter; heterologous human-transporter HEK cell assays.

limitations

An inhibition concentration in culture is not a dietary threshold or proof of reduced brain serine.

nutrient_topic

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

plain_language

Threonine can compete with serine in a defined transporter assay.

primary_references

D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27272177/ · DOI 10.1371/journal.pone.0156551

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 26–32

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Table 5: three observations per transporter; heterologous human-transporter HEK cell assays. · source_derived_draft · unverified_draft

## l-threonine-serine-competition-slc1a4 Threonine can compete with serine in a defined transporter assay. L-threonine inhibited radiolabeled L-serine uptake in HEK cells expressing human ASCT1, with an IC50 of 181 ± 75 micromolar. Model: Table 5: three observations per transporter; heterologous human-transporter HEK cell assays. Limitations: An inhibition concentration in culture is not a dietary threshold or proof of reduced brain serine. Evidence access: Primary full-text Table 5, publisher PDF D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27272177/ · DOI 10.1371/journal.pone.0156551

evidence_access

Primary full-text Table 5, publisher PDF

experimental_model

Table 5: three observations per transporter; heterologous human-transporter HEK cell assays.

limitations

An inhibition concentration in culture is not a dietary threshold or proof of reduced brain serine.

nutrient_topic

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

plain_language

Threonine can compete with serine in a defined transporter assay.

primary_references

D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27272177/ · DOI 10.1371/journal.pone.0156551

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 34–40

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Table 5: three observations per transporter; heterologous human-transporter HEK cell assays. · source_derived_draft · unverified_draft

## l-threonine-serine-competition-slc1a5 Threonine can compete with serine in a defined transporter assay. L-threonine inhibited radiolabeled L-serine uptake in HEK cells expressing human ASCT2, with an IC50 of 228 ± 83 micromolar. Model: Table 5: three observations per transporter; heterologous human-transporter HEK cell assays. Limitations: An inhibition concentration in culture is not a dietary threshold or proof of reduced brain serine. Evidence access: Primary full-text Table 5, publisher PDF D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27272177/ · DOI 10.1371/journal.pone.0156551

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse xenografts linked to human glioblastoma stem-cell experiments.

limitations

This study does not establish a safe or effective threonine-restricted diet for patients. Exact dietary protocol and drug schedules require full-text clinical translation review.

nutrient_topic

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

plain_language

Tumor dependency led to an experimental dietary intervention in animals.

primary_references

Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38519786/ · DOI 10.1038/s43018-024-00748-7

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 370–376

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse xenografts linked to human glioblastoma stem-cell experiments. · source_derived_draft · unverified_draft

## l-threonine-tumor-threonine-restriction Tumor dependency led to an experimental dietary intervention in animals. Dietary threonine restriction reduced tumor t6A and slowed glioblastoma xenograft growth, augmenting tested chemotherapy and anti-mitotic therapy. Model: Mouse xenografts linked to human glioblastoma stem-cell experiments. Limitations: This study does not establish a safe or effective threonine-restricted diet for patients. Exact dietary protocol and drug schedules require full-text clinical translation review. Evidence access: Primary abstract Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38519786/ · DOI 10.1038/s43018-024-00748-7

evidence_access

Primary abstract

experimental_model

Human cDNA cloning and transporter characterization.

limitations

Substrate overlap alone does not quantify competition during ordinary dietary intake.

nutrient_topic

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

plain_language

Several amino acids share a cellular entry and exchange route.

primary_references

Human neutral amino acid transporter ASCT1: structure of the gene (SLC1A4) and localization to chromosome 2p13-p15. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7896285/ · DOI 10.1006/geno.1994.1577

transport_effect

depends A substrate-selectivity record. ASCT1 is an obligatory exchanger and no direction is stated.

transport_pool

the cytosol across the plasma membrane A substrate-selectivity record. ASCT1 is an obligatory exchanger and no direction is stated.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 18–24

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cDNA cloning and transporter characterization. · source_derived_draft · unverified_draft

## l-threonine-asct1-substrate Several amino acids share a cellular entry and exchange route. Cloned human ASCT1 transported alanine, serine, cysteine and threonine rather than glutamate or aspartate. Model: Human cDNA cloning and transporter characterization. Limitations: Substrate overlap alone does not quantify competition during ordinary dietary intake. Evidence access: Primary abstract Human neutral amino acid transporter ASCT1: structure of the gene (SLC1A4) and localization to chromosome 2p13-p15. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7896285/ · DOI 10.1006/geno.1994.1577

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full-text Figure 3 results excerpt

experimental_model

Primary-paper Figure 3 isotope tracing and Acsf3-deficient mouse hepatocytes.

limitations

This mouse experiment must not be summarized as proven human threonine depletion or a clinical treatment.

nutrient_topic

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

plain_language

A downstream metabolic defect changed how threonine carbon accumulated.

primary_references

An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 402–408

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary-paper Figure 3 isotope tracing and Acsf3-deficient mouse hepatocytes. · source_derived_draft · unverified_draft

## l-threonine-acsf3-methylmalonate A downstream metabolic defect changed how threonine carbon accumulated. Acsf3 depletion increased labeled-threonine conversion to methylmalonic acid in mouse primary hepatocytes. Model: Primary-paper Figure 3 isotope tracing and Acsf3-deficient mouse hepatocytes. Limitations: This mouse experiment must not be summarized as proven human threonine depletion or a clinical treatment. Evidence access: Primary full-text Figure 3 results excerpt An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40403731/ · DOI 10.1016/j.xgen.2025.100855

evidence_access

Primary abstract

experimental_model

Reconstituted enzyme kinetics and bicarbonate-deprived human cell culture.

limitations

The culture manipulation is not a bicarbonate supplementation trial or a clinical intracellular threshold.

nutrient_topic

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

plain_language

An additional substrate can limit the threonine-dependent reaction.

primary_references

CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 138–144

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Reconstituted enzyme kinetics and bicarbonate-deprived human cell culture. · source_derived_draft · unverified_draft

## l-threonine-bicarbonate-limitation An additional substrate can limit the threonine-dependent reaction. The measured bicarbonate/CO2 Km for t6A37 formation was 31 millimolar; human cells cultured without bicarbonate had less t6A37 in mitochondrial tRNAs. Model: Reconstituted enzyme kinetics and bicarbonate-deprived human cell culture. Limitations: The culture manipulation is not a bicarbonate supplementation trial or a clinical intracellular threshold. Evidence access: Primary abstract CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

evidence_access

Primary abstract

experimental_model

Enzyme biochemistry, structures, cellular assays and zebrafish work.

limitations

Anti-angiogenic action could be separated from toxicity with selected derivatives; these are experimental agents, not routine nutrient interactions.

nutrient_topic

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

plain_language

Blocking amino-acid processing can mimic inadequate supply inside a cell.

primary_references

Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26271225/ · DOI 10.1038/srep13160

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 394–400

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Enzyme biochemistry, structures, cellular assays and zebrafish work. · source_derived_draft · unverified_draft

## l-threonine-borrelidin-competition Blocking amino-acid processing can mimic inadequate supply inside a cell. Borrelidin-class inhibitor toxicity was linked to competition with threonine at TARS, provoking amino-acid-starvation responses and apoptosis in the studied systems. Model: Enzyme biochemistry, structures, cellular assays and zebrafish work. Limitations: Anti-angiogenic action could be separated from toxicity with selected derivatives; these are experimental agents, not routine nutrient interactions. Evidence access: Primary abstract Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26271225/ · DOI 10.1038/srep13160

evidence_access

Primary abstract

experimental_model

Primary human genetics and structural study of the t6A pathway.

limitations

OSGEP and mitochondrial OSGEPL1 are distinct proteins; threonyl-tRNA loading is a separate reaction.

nutrient_topic

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

plain_language

The cytosol uses a different downstream machine from the mitochondrial pathway.

primary_references

Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 442–448

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary human genetics and structural study of the t6A pathway. · source_derived_draft · unverified_draft

## l-threonine-cytosolic-keops The cytosol uses a different downstream machine from the mitochondrial pathway. Cytosolic t6A formation uses sequential YRDC and OSGEP activities, with OSGEP operating within the KEOPS complex. Model: Primary human genetics and structural study of the t6A pathway. Limitations: OSGEP and mitochondrial OSGEPL1 are distinct proteins; threonyl-tRNA loading is a separate reaction. Evidence access: Primary abstract Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human mutant crystal structure, NMR and molecular-dynamics analysis.

limitations

No correction of this defect by threonine supplementation was demonstrated.

nutrient_topic

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

plain_language

A sugar donor and amino-acid-containing protein are insufficient if the modifying enzyme cannot bind correctly.

primary_references

Structural Analysis of a GalNAc-T2 Mutant Reveals an Induced-Fit Catalytic Mechanism for GalNAc-Ts. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29601100/ · DOI 10.1002/chem.201800701

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 194–200

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human mutant crystal structure, NMR and molecular-dynamics analysis. · source_derived_draft · unverified_draft

## l-threonine-galnt2-f104s A sugar donor and amino-acid-containing protein are insufficient if the modifying enzyme cannot bind correctly. GALNT2 F104S disrupted the UDP-GalNAc-dependent active conformation and peptide-substrate binding. Model: Human mutant crystal structure, NMR and molecular-dynamics analysis. Limitations: No correction of this defect by threonine supplementation was demonstrated. Evidence access: Primary abstract Structural Analysis of a GalNAc-T2 Mutant Reveals an Induced-Fit Catalytic Mechanism for GalNAc-Ts. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29601100/ · DOI 10.1002/chem.201800701

evidence_access

Primary abstract

experimental_model

Human GalNAc-T2 structural and NMR enzymology.

limitations

Free dietary threonine is not the glycosyltransferase acceptor used in this protein-modification reaction.

nutrient_topic

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

plain_language

A threonine residue already built into a protein can carry a sugar.

primary_references

Structural Analysis of a GalNAc-T2 Mutant Reveals an Induced-Fit Catalytic Mechanism for GalNAc-Ts. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29601100/ · DOI 10.1002/chem.201800701

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 186–192

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human GalNAc-T2 structural and NMR enzymology. · source_derived_draft · unverified_draft

## l-threonine-galnt2-sugar A threonine residue already built into a protein can carry a sugar. GalNAc-T2 initiates mucin-type O-glycosylation by transferring GalNAc from UDP-GalNAc to serine or threonine residues within proteins. Model: Human GalNAc-T2 structural and NMR enzymology. Limitations: Free dietary threonine is not the glycosyltransferase acceptor used in this protein-modification reaction. Evidence access: Primary abstract Structural Analysis of a GalNAc-T2 Mutant Reveals an Induced-Fit Catalytic Mechanism for GalNAc-Ts. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29601100/ · DOI 10.1002/chem.201800701

evidence_access

Primary abstract

experimental_model

Crystal structure and cellular characterization of human KEOPS components.

limitations

The structural observation supports a stabilizing role; it does not establish that extra threonine repairs a subunit defect.

nutrient_topic

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

plain_language

An organizing subunit helps assemble the RNA-modifying machine.

primary_references

Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 450–456

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Crystal structure and cellular characterization of human KEOPS components. · source_derived_draft · unverified_draft

## l-threonine-gon7-complex An organizing subunit helps assemble the RNA-modifying machine. Human GON7 became partly structured upon binding LAGE3 in the GON7/LAGE3/OSGEP subcomplex, supporting its proposed role in KEOPS stability and organization. Model: Crystal structure and cellular characterization of human KEOPS components. Limitations: The structural observation supports a stabilizing role; it does not establish that extra threonine repairs a subunit defect. Evidence access: Primary abstract Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x

evidence_access

Primary abstract

experimental_model

Comparative human and mouse gene characterization.

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 282–288

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Comparative human and mouse gene characterization. · source_derived_draft · unverified_draft

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

evidence_access

Primary abstract

experimental_model

Human recombinant enzymes expressed in E. coli and compared biochemically.

limitations

Activity in a purified system does not quantify whole-body human threonine flux. The threonine product is alpha-ketobutyrate, distinct from the serine product pyruvate.

nutrient_topic

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

plain_language

Threonine can enter carbon metabolism through an enzyme it shares with serine.

primary_references

Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 250–256

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant enzymes expressed in E. coli and compared biochemically. · source_derived_draft · unverified_draft

## l-threonine-human-sds-catabolism Threonine can enter carbon metabolism through an enzyme it shares with serine. Purified human hepatic serine dehydratase showed L-threonine dehydratase activity in comparison with the human SDH-like isoform. Model: Human recombinant enzymes expressed in E. coli and compared biochemically. Limitations: Activity in a purified system does not quantify whole-body human threonine flux. The threonine product is alpha-ketobutyrate, distinct from the serine product pyruvate. Evidence access: Primary abstract Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

evidence_access

Primary abstract

experimental_model

Purified wild-type and engineered human enzymes.

limitations

This manipulation does not show that additional B6 restores a mutant enzyme or that ordinary dietary B6 is limiting.

nutrient_topic

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

plain_language

B6-dependent chemistry also depends on the enzyme structure that binds its cofactor.

primary_references

Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 266–272

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified wild-type and engineered human enzymes. · source_derived_draft · unverified_draft

## l-threonine-human-sds-plp B6-dependent chemistry also depends on the enzyme structure that binds its cofactor. Deleting Pro128 from human hepatic SDS changed substrate kinetic constants and affinity for pyridoxal phosphate. Model: Purified wild-type and engineered human enzymes. Limitations: This manipulation does not show that additional B6 restores a mutant enzyme or that ordinary dietary B6 is limiting. Evidence access: Primary abstract Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

evidence_access

Primary abstract

experimental_model

Comparative human enzyme kinetics and PLP-binding measurements.

limitations

Isoform abundance in cultured cells was low; catalytic capacity does not establish its dominant tissue role.

nutrient_topic

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

plain_language

Closely related enzymes can process the same substrate at different rates.

primary_references

Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 258–264

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Comparative human enzyme kinetics and PLP-binding measurements. · source_derived_draft · unverified_draft

## l-threonine-human-sdsl-catabolism Closely related enzymes can process the same substrate at different rates. The recombinant human SDH-like protein also had threonine dehydratase activity, with kinetic constants differing substantially from hepatic SDS. Model: Comparative human enzyme kinetics and PLP-binding measurements. Limitations: Isoform abundance in cultured cells was low; catalytic capacity does not establish its dominant tissue role. Evidence access: Primary abstract Enzymatic and biochemical properties of a novel human serine dehydratase isoform. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16580895/ · DOI 10.1016/j.bbapap.2006.02.010

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

An expressed gene is not necessarily a functioning metabolic route.

primary_references

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

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 274–280

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cDNA/genomic analysis; exon-6 splice-site loss in all 23 genotyped individuals. · source_derived_draft · unverified_draft

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

evidence_access

Primary abstract

experimental_model

Purified kinase and isolated-adipocyte assays; species unverified from abstract.

limitations

This does not prove that a threonine supplement changes BCAA oxidation in humans. Correction record: PubMed indexes an erratum in Biochemical Journal 1987;242(3):935. The notice text was inaccessible during this curation; its specific scope and impact remain unverified. The purified-enzyme findings are retained provisionally with this flag, and the abstract does not identify the source species. https://pubmed.ncbi.nlm.nih.gov/3800905/

nutrient_topic

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

plain_language

A catabolic intermediate can influence the regulatory brake on its disposal machinery.

primary_references

Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3800905/ · DOI 10.1042/bj2370621

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 314–320

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified kinase and isolated-adipocyte assays; species unverified from abstract. · source_derived_draft · unverified_draft

## l-threonine-ketoacid-feedback A catabolic intermediate can influence the regulatory brake on its disposal machinery. 2-Oxobutyrate inhibited BCOADC kinase, and reduced BCOADC phosphorylation was observed in isolated adipocytes. Model: Purified kinase and isolated-adipocyte assays; species unverified from abstract. Limitations: This does not prove that a threonine supplement changes BCAA oxidation in humans. Correction record: PubMed indexes an erratum in Biochemical Journal 1987;242(3):935. The notice text was inaccessible during this curation; its specific scope and impact remain unverified. The purified-enzyme findings are retained provisionally with this flag, and the abstract does not identify the source species. https://pubmed.ncbi.nlm.nih.gov/3800905/ Evidence access: Primary abstract Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3800905/ · DOI 10.1042/bj2370621

evidence_access

Primary abstract

experimental_model

Purified-enzyme comparison; source species is not specified in the accessible abstract.

limitations

This is not recorded as direct human enzyme evidence or an exclusive BCKDH route. Correction record: PubMed indexes an erratum in Biochemical Journal 1987;242(3):935. The notice text was inaccessible during this curation; its specific scope and impact remain unverified. The purified-enzyme findings are retained provisionally with this flag, and the abstract does not identify the source species. https://pubmed.ncbi.nlm.nih.gov/3800905/

nutrient_topic

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

plain_language

More than one ketoacid complex can handle this carbon skeleton in vitro.

primary_references

Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3800905/ · DOI 10.1042/bj2370621

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 306–312

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-enzyme comparison; source species is not specified in the accessible abstract. · source_derived_draft · unverified_draft

## l-threonine-ketoacid-oxidation More than one ketoacid complex can handle this carbon skeleton in vitro. Purified BCOADC oxidized 2-oxobutyrate with a reported Km of 18 micromolar; purified PDC also accepted it, whereas OGDH did not. Model: Purified-enzyme comparison; source species is not specified in the accessible abstract. Limitations: This is not recorded as direct human enzyme evidence or an exclusive BCKDH route. Correction record: PubMed indexes an erratum in Biochemical Journal 1987;242(3):935. The notice text was inaccessible during this curation; its specific scope and impact remain unverified. The purified-enzyme findings are retained provisionally with this flag, and the abstract does not identify the source species. https://pubmed.ncbi.nlm.nih.gov/3800905/ Evidence access: Primary abstract Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3800905/ · DOI 10.1042/bj2370621

evidence_access

Primary abstract

experimental_model

Ex vivo pig tissue; amino-acid uptake inhibition experiment.

limitations

This does not show that normal methionine intake causes human threonine deficiency.

nutrient_topic

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

plain_language

A different essential amino acid can compete at the intestinal transport step.

primary_references

Transport of Neutral Amino Acids in the Jejunum of Pigs with Special Consideration of L-Methionine. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39408384/ · DOI 10.3390/nu16193418

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 50–56

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ex vivo pig tissue; amino-acid uptake inhibition experiment. · source_derived_draft · unverified_draft

## l-threonine-methionine-competition A different essential amino acid can compete at the intestinal transport step. Mucosal L-methionine inhibited threonine uptake in the pig jejunal transport experiments. Model: Ex vivo pig tissue; amino-acid uptake inhibition experiment. Limitations: This does not show that normal methionine intake causes human threonine deficiency. Evidence access: Primary abstract Transport of Neutral Amino Acids in the Jejunum of Pigs with Special Consideration of L-Methionine. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39408384/ · DOI 10.3390/nu16193418

evidence_access

Primary abstract

experimental_model

Mutant pathway analysis and enzyme characterization.

limitations

Whether this pathway changes human host exposure depends on community, substrate supply and environmental conditions.

nutrient_topic

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

plain_language

A microbial fermentation step releases energy as well as a short-chain fatty acid.

primary_references

Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9484901/ · DOI 10.1046/j.1365-2958.1998.00696.x

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 434–440

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mutant pathway analysis and enzyme characterization. · source_derived_draft · unverified_draft

## l-threonine-microbial-atp A microbial fermentation step releases energy as well as a short-chain fatty acid. E. coli TdcD or AckA converted propionyl phosphate to propionate with ATP generation in the anaerobic threonine-degradation pathway. Model: Mutant pathway analysis and enzyme characterization. Limitations: Whether this pathway changes human host exposure depends on community, substrate supply and environmental conditions. Evidence access: Primary abstract Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9484901/ · DOI 10.1046/j.1365-2958.1998.00696.x

evidence_access

Primary abstract

experimental_model

E. coli operon analysis, mutants, enzyme assays and culture-supernatant NMR.

limitations

This is not a human enzyme reaction or a measurement of net propionate production in the human gut.

nutrient_topic

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

plain_language

Microbes have a separate route for fermenting threonine carbon.

primary_references

Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9484901/ · DOI 10.1046/j.1365-2958.1998.00696.x

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 426–432

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · E. coli operon analysis, mutants, enzyme assays and culture-supernatant NMR. · source_derived_draft · unverified_draft

## l-threonine-microbial-ketoacid Microbes have a separate route for fermenting threonine carbon. E. coli mutant and enzyme studies showed TdcE conversion of threonine-derived 2-ketobutyrate into propionyl-CoA during anaerobic growth. Model: E. coli operon analysis, mutants, enzyme assays and culture-supernatant NMR. Limitations: This is not a human enzyme reaction or a measurement of net propionate production in the human gut. Evidence access: Primary abstract Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9484901/ · DOI 10.1046/j.1365-2958.1998.00696.x

evidence_access

Primary abstract

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 322–328

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic stem-cell metabolism and amino-acid withdrawal experiments. · source_derived_draft · unverified_draft

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Mouse embryonic stem-cell Tdh depletion, alongside dietary-substrate tracing in the same study.

limitations

The experiment and threonine withdrawal are complementary tests from one paper, not independent laboratories.

nutrient_topic

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

plain_language

The precursor requires an active metabolic pathway to affect the downstream mark.

primary_references

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

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 338–344

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse embryonic stem-cell Tdh depletion, alongside dietary-substrate tracing in the same study. · source_derived_draft · unverified_draft

## l-threonine-mouse-tdh-methylation The precursor requires an active metabolic pathway to affect the downstream mark. Depleting Tdh also lowered SAM and H3K4 trimethylation in the mouse stem-cell experiments. Model: Mouse embryonic stem-cell Tdh depletion, alongside dietary-substrate tracing in the same study. Limitations: The experiment and threonine withdrawal are complementary tests from one paper, not independent laboratories. Evidence access: Primary abstract Influence of threonine metabolism on S-adenosylmethionine and histone methylation. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23118012/ · DOI 10.1126/science.1226603

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human HEK293T knockout and tRNA modification/aminoacylation measurements.

limitations

The result identifies a tRNA-modification requirement, not a dietary lysine shortage.

nutrient_topic

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

plain_language

Threonine-derived chemistry supports the handling of another amino acid too.

primary_references

Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 154–160

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T knockout and tRNA modification/aminoacylation measurements. · source_derived_draft · unverified_draft

## l-threonine-osgepl1-charging Threonine-derived chemistry supports the handling of another amino acid too. OSGEPL1 deletion in HEK293T cells reduced aminoacylation of mitochondrial tRNA Thr and tRNA Lys and altered other tRNA modifications. Model: Human HEK293T knockout and tRNA modification/aminoacylation measurements. Limitations: The result identifies a tRNA-modification requirement, not a dietary lysine shortage. Evidence access: Primary abstract Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human HEK293T knockout; mitochondrial protein and translation analyses.

limitations

Knockout cells remained viable; physiological consequences cannot be inferred from mistranslation alone.

nutrient_topic

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

plain_language

Loss of an RNA mark can change translation accuracy as well as speed.

primary_references

Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 162–168

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T knockout; mitochondrial protein and translation analyses. · source_derived_draft · unverified_draft

## l-threonine-osgepl1-fidelity Loss of an RNA mark can change translation accuracy as well as speed. Mitochondrial t6A37 hypomodification after OSGEPL1 deletion caused near-cognate codon misreading and amino-acid misincorporation. Model: Human HEK293T knockout; mitochondrial protein and translation analyses. Limitations: Knockout cells remained viable; physiological consequences cannot be inferred from mistranslation alone. Evidence access: Primary abstract Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human knockout cell experiments.

limitations

Loss of the enzyme is not equivalent to inadequate dietary threonine.

nutrient_topic

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

plain_language

An amino-acid-derived RNA mark depends on its own installing enzyme.

primary_references

CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 146–152

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

## l-threonine-osgepl1-loss An amino-acid-derived RNA mark depends on its own installing enzyme. OSGEPL1 knockout reduced mitochondrial translation and impaired respiration in human cells. Model: Human knockout cell experiments. Limitations: Loss of the enzyme is not equivalent to inadequate dietary threonine. Evidence access: Primary abstract CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Genetic complementation of knockout cells.

limitations

The same study observed translation disruption without overt baseline heart deficiency in Osgepl1-deleted mice; tissue and challenge matter.

nutrient_topic

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

plain_language

Restoring a protein helps only if it retains the required molecular function.

primary_references

Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism 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 · Genetic complementation of knockout cells. · source_derived_draft · unverified_draft

## l-threonine-osgepl1-rescue Restoring a protein helps only if it retains the required molecular function. Wild-type OSGEPL1 restored mitochondrial function, whereas a tRNA-binding-defective OSGEPL1 construct did not. Model: Genetic complementation of knockout cells. Limitations: The same study observed translation disruption without overt baseline heart deficiency in Osgepl1-deleted mice; tissue and challenge matter. Evidence access: Primary abstract Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

evidence_access

Primary abstract

experimental_model

Jejunum from male castrated Pietrain × Danbred pigs receiving different methionine supplements.

limitations

Tissue flux integrates several transporters; it does not identify one exclusive threonine carrier.

nutrient_topic

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

plain_language

An ion gradient contributes to intestinal amino-acid movement.

primary_references

Transport of Neutral Amino Acids in the Jejunum of Pigs with Special Consideration of L-Methionine. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39408384/ · DOI 10.3390/nu16193418

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 42–48

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Jejunum from male castrated Pietrain × Danbred pigs receiving different methionine supplements. · source_derived_draft · unverified_draft

## l-threonine-pig-sodium-uptake An ion gradient contributes to intestinal amino-acid movement. Ex vivo pig jejunal L-threonine flux was sodium dependent in assays using 50 micromolar and 5 millimolar amino-acid concentrations. Model: Jejunum from male castrated Pietrain × Danbred pigs receiving different methionine supplements. Limitations: Tissue flux integrates several transporters; it does not identify one exclusive threonine carrier. Evidence access: Primary abstract Transport of Neutral Amino Acids in the Jejunum of Pigs with Special Consideration of L-Methionine. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39408384/ · DOI 10.3390/nu16193418

evidence_access

Primary abstract

experimental_model

Human enzyme biochemistry alongside inhibitor structures and cellular studies.

limitations

The charging reaction and extracellular signaling by the enzyme are separate functions.

nutrient_topic

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

plain_language

The amino acid must be attached to its matching tRNA before translation.

primary_references

Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26271225/ · DOI 10.1038/srep13160

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 58–64

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme biochemistry alongside inhibitor structures and cellular studies. · source_derived_draft · unverified_draft

## l-threonine-tars1-charging The amino acid must be attached to its matching tRNA before translation. Human cytosolic TARS aminoacylation assays measured threonine loading onto tRNA and competitive inhibition by borrelidin-class compounds. Model: Human enzyme biochemistry alongside inhibitor structures and cellular studies. Limitations: The charging reaction and extracellular signaling by the enzyme are separate functions. Evidence access: Primary abstract Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26271225/ · DOI 10.1038/srep13160

evidence_access

Primary abstract

experimental_model

Human endothelial assays and chick membrane model.

limitations

Enzyme exposure is not amino-acid supplementation; no claim of dietary cancer causation is made.

nutrient_topic

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

plain_language

The same enzyme has an extracellular signaling role.

primary_references

Secreted Threonyl-tRNA synthetase stimulates endothelial cell migration and angiogenesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23425968/ · DOI 10.1038/srep01317

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 386–392

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human endothelial assays and chick membrane model. · source_derived_draft · unverified_draft

## l-threonine-tars1-extracellular The same enzyme has an extracellular signaling role. Exogenous TARS promoted endothelial migration and angiogenesis in culture and chick chorioallantoic membrane assays. Model: Human endothelial assays and chick membrane model. Limitations: Enzyme exposure is not amino-acid supplementation; no claim of dietary cancer causation is made. Evidence access: Primary abstract Secreted Threonyl-tRNA synthetase stimulates endothelial cell migration and angiogenesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23425968/ · DOI 10.1038/srep01317

evidence_access

Primary abstract

experimental_model

Human vascular endothelial cell culture.

limitations

This is secretion of the enzyme, not secretion of threonine or proof that dietary threonine triggers the process.

nutrient_topic

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

plain_language

A protein that loads threonine can also leave the cell under signaling conditions.

primary_references

Secreted Threonyl-tRNA synthetase stimulates endothelial cell migration and angiogenesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23425968/ · DOI 10.1038/srep01317

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 378–384

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human vascular endothelial cell culture. · source_derived_draft · unverified_draft

## l-threonine-tars1-secretion A protein that loads threonine can also leave the cell under signaling conditions. Human endothelial cells secreted TARS after TNF-alpha or VEGF exposure. Model: Human vascular endothelial cell culture. Limitations: This is secretion of the enzyme, not secretion of threonine or proof that dietary threonine triggers the process. Evidence access: Primary abstract Secreted Threonyl-tRNA synthetase stimulates endothelial cell migration and angiogenesis. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23425968/ · DOI 10.1038/srep01317

evidence_access

Primary abstract

experimental_model

Biochemical interaction and RNA immunoprecipitation/sequencing analyses in vertebrate models.

limitations

This scaffold function is not evidence that adding free threonine increases translation of the same targets.

nutrient_topic

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

plain_language

A tRNA-loading enzyme can also help organize translation initiation.

primary_references

A threonyl-tRNA synthetase-mediated translation initiation machinery. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30902983/ · DOI 10.1038/s41467-019-09086-0

L-Threonine: translation, intestinal barrier, metabolism 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 · Biochemical interaction and RNA immunoprecipitation/sequencing analyses in vertebrate models. · source_derived_draft · unverified_draft

## l-threonine-tars1-translation-scaffold A tRNA-loading enzyme can also help organize translation initiation. Threonyl-tRNA synthetase interacted with 4EHP and recruited initiation components into a translation-initiation machinery that selected target mRNAs. Model: Biochemical interaction and RNA immunoprecipitation/sequencing analyses in vertebrate models. Limitations: This scaffold function is not evidence that adding free threonine increases translation of the same targets. Evidence access: Primary abstract A threonyl-tRNA synthetase-mediated translation initiation machinery. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30902983/ · DOI 10.1038/s41467-019-09086-0

evidence_access

Primary abstract

experimental_model

Human TARS2 functional characterization and disease-variant assays.

limitations

Cytosolic TARS1 does not replace this mitochondrial record.

nutrient_topic

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

plain_language

Mitochondria have their own threonine-loading enzyme.

primary_references

Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 66–72

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TARS2 functional characterization and disease-variant assays. · source_derived_draft · unverified_draft

## l-threonine-tars2-charging Mitochondria have their own threonine-loading enzyme. Human TARS2 generates mitochondrial Thr-tRNA Thr for mitochondrial translation. Model: Human TARS2 functional characterization and disease-variant assays. Limitations: Cytosolic TARS1 does not replace this mitochondrial record. Evidence access: Primary abstract Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

evidence_access

Primary abstract

experimental_model

Human mitochondrial aminoacyl-tRNA synthetase biochemistry.

limitations

This is tRNA-bound substrate discrimination, not evidence that serine supplements cause mistranslation.

nutrient_topic

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

plain_language

Proofreading removes serine accidentally attached to threonine tRNA.

primary_references

Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 74–80

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human mitochondrial aminoacyl-tRNA synthetase biochemistry. · source_derived_draft · unverified_draft

## l-threonine-tars2-editing Proofreading removes serine accidentally attached to threonine tRNA. Human TARS2 clears mischarged Ser-tRNA Thr during mitochondrial translation. Model: Human mitochondrial aminoacyl-tRNA synthetase biochemistry. Limitations: This is tRNA-bound substrate discrimination, not evidence that serine supplements cause mistranslation. Evidence access: Primary abstract Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues.

limitations

GSNO is not reduced glutathione; this exposure does not predict effects of oral glutathione. H2O2 resistance and GSNO sensitivity were distinct in this study.

nutrient_topic

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

plain_language

Chemical modification of the enzyme can disrupt loading and proofreading.

primary_references

Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32484546/ · DOI 10.1093/nar/gkaa471

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 90–96

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues. · source_derived_draft · unverified_draft

## l-threonine-tars2-nitrosation Chemical modification of the enzyme can disrupt loading and proofreading. GSNO treatment S-nitrosated human mitochondrial ThrRS and reduced both aminoacylation and editing activity in vitro. Model: Purified human enzyme; four modified cysteine residues; corroborating S-nitrosation detection in human cells and mouse tissues. Limitations: GSNO is not reduced glutathione; this exposure does not predict effects of oral glutathione. H2O2 resistance and GSNO sensitivity were distinct in this study. Evidence access: Primary abstract Nitrosative stress inhibits aminoacylation and editing activities of mitochondrial threonyl-tRNA synthetase by S-nitrosation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32484546/ · DOI 10.1093/nar/gkaa471

evidence_access

Primary abstract

experimental_model

Cellular interaction and mTORC1 signaling experiments.

limitations

GTP-bound RagC here belongs to the inactive Rag configuration; GTP status has different implications for RagA and RagC.

nutrient_topic

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

plain_language

A threonine-processing protein also links nutrient availability to a growth-control switch.

primary_references

Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 98–104

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cellular interaction and mTORC1 signaling experiments. · source_derived_draft · unverified_draft

## l-threonine-tars2-rag A threonine-processing protein also links nutrient availability to a growth-control switch. TARS2 interacted with inactive Rag complexes, especially GTP-bound RagC, and promoted RagA GTP loading. Model: Cellular interaction and mTORC1 signaling experiments. Limitations: GTP-bound RagC here belongs to the inactive Rag configuration; GTP status has different implications for RagA and RagC. Evidence access: Primary abstract Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

18 newly reported individuals from 15 families, prior cases reviewed, in vitro assays and zebrafish modeling.

limitations

Likely mechanistic contribution, not proof that this pathway explains every patient feature.

nutrient_topic

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

plain_language

Some variants can affect signaling as well as the usual translation function.

primary_references

Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37454282/ · DOI 10.1016/j.gim.2023.100938

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism 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 · 18 newly reported individuals from 15 families, prior cases reviewed, in vitro assays and zebrafish modeling. · source_derived_draft · unverified_draft

## l-threonine-tars2-rag-variants Some variants can affect signaling as well as the usual translation function. Disease-associated variants within TARS2 residues 301–381 reduced Rag binding in vitro; the associated mTORC1 mechanism was also investigated in zebrafish. Model: 18 newly reported individuals from 15 families, prior cases reviewed, in vitro assays and zebrafish modeling. Limitations: Likely mechanistic contribution, not proof that this pathway explains every patient feature. Evidence access: Primary abstract Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37454282/ · DOI 10.1016/j.gim.2023.100938

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

TARS2 loss and threonine repletion in cultured cells.

limitations

This is a signaling endpoint, not a clinical threonine-repletion trial.

nutrient_topic

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

plain_language

Restoring the nutrient did not restore the signal when its machinery was missing.

primary_references

Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 106–112

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · TARS2 loss and threonine repletion in cultured cells. · source_derived_draft · unverified_draft

## l-threonine-tars2-repletion-failure Restoring the nutrient did not restore the signal when its machinery was missing. Cells lacking TARS2 failed to restore mTORC1 activation in response to threonine repletion; cytosolic TARS was not required for this signaling effect. Model: TARS2 loss and threonine repletion in cultured cells. Limitations: This is a signaling endpoint, not a clinical threonine-repletion trial. Evidence access: Primary abstract Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33340489/ · DOI 10.1016/j.molcel.2020.11.036

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis.

limitations

Disease mechanisms differ by variant; response to threonine supplementation was not established.

nutrient_topic

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

plain_language

Enough amino acid cannot by itself guarantee a working loading enzyme.

primary_references

Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 82–88

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis. · source_derived_draft · unverified_draft

## l-threonine-tars2-variants Enough amino acid cannot by itself guarantee a working loading enzyme. Seven newly reported TARS2 variants were linked to mitochondrial disease, with functional studies demonstrating impaired protein stability or function. Model: Five unrelated patients; one nonsense and six missense variants; biochemical and functional analysis. Limitations: Disease mechanisms differ by variant; response to threonine supplementation was not established. Evidence access: Primary abstract Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34508595/ · DOI 10.1093/hmg/ddab257

evidence_access

Primary abstract and accessible primary-paper pathway description

experimental_model

Primary paper pathway description supporting human mitochondrial experiments.

limitations

The reaction sequence is described in the primary paper introduction; the 2024 study primarily tests loss of the downstream enzyme.

nutrient_topic

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

plain_language

An activated intermediate links nutrient supply to an RNA modification.

primary_references

Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 130–136

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary paper pathway description supporting human mitochondrial experiments. · source_derived_draft · unverified_draft

## l-threonine-trna-intermediate An activated intermediate links nutrient supply to an RNA modification. The t6A pathway first forms threonylcarbamoyladenylate from threonine, bicarbonate and ATP; OSGEPL1 then transfers the threonylcarbamoyl group to mitochondrial tRNA A37. Model: Primary paper pathway description supporting human mitochondrial experiments. Limitations: The reaction sequence is described in the primary paper introduction; the 2024 study primarily tests loss of the downstream enzyme. Evidence access: Primary abstract and accessible primary-paper pathway description Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38227555/ · DOI 10.1093/nar/gkae013

evidence_access

Primary abstract

experimental_model

Human mitochondrial tRNA-modification reconstitution and cellular experiments.

limitations

The mark occurs on multiple tRNAs; it is not restricted to the tRNA that carries threonine.

nutrient_topic

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

plain_language

Threonine helps make a decoding mark on tRNA, separate from being loaded for protein synthesis.

primary_references

CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

L-Threonine: translation, intestinal barrier, metabolism 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 mitochondrial tRNA-modification reconstitution and cellular experiments. · source_derived_draft · unverified_draft

## l-threonine-trna-mark-substrates Threonine helps make a decoding mark on tRNA, separate from being loaded for protein synthesis. Human YRDC and OSGEPL1 supported mitochondrial t6A37 formation using L-threonine, ATP and CO2/bicarbonate as substrates. Model: Human mitochondrial tRNA-modification reconstitution and cellular experiments. Limitations: The mark occurs on multiple tRNAs; it is not restricted to the tRNA that carries threonine. Evidence access: Primary abstract CO2-sensitive tRNA modification associated with human mitochondrial disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29760464/ · DOI 10.1038/s41467-018-04250-4

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

CRISPR screen, cultured glioblastoma stem cells and xenografts.

limitations

Genetic targeting of YRDC is distinct from nutritional restriction and from a demonstrated human cancer treatment.

nutrient_topic

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

plain_language

A tumor model depended on the machinery that uses threonine to modify tRNA.

primary_references

Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38519786/ · DOI 10.1038/s43018-024-00748-7

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 362–368

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · CRISPR screen, cultured glioblastoma stem cells and xenografts. · source_derived_draft · unverified_draft

## l-threonine-yrdc-glioblastoma A tumor model depended on the machinery that uses threonine to modify tRNA. Targeting YRDC reduced t6A, translation and tumor growth in glioblastoma stem-cell cultures and in vivo tumor models. Model: CRISPR screen, cultured glioblastoma stem cells and xenografts. Limitations: Genetic targeting of YRDC is distinct from nutritional restriction and from a demonstrated human cancer treatment. Evidence access: Primary abstract Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38519786/ · DOI 10.1038/s43018-024-00748-7

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human genetic disease study with functional analyses; GON7-associated cases were milder in the reported series.

limitations

This is an inherited machinery disorder, not demonstrated dietary threonine deficiency or a proven supplementation-responsive syndrome.

nutrient_topic

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

plain_language

A threonine-using RNA pathway matters in human brain and kidney development.

primary_references

Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 458–464

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human genetic disease study with functional analyses; GON7-associated cases were milder in the reported series. · source_derived_draft · unverified_draft

## l-threonine-yrdc-inherited-disease A threonine-using RNA pathway matters in human brain and kidney development. Inherited YRDC mutations were associated with severe Galloway–Mowat syndrome, linking t6A machinery impairment with microcephaly and early-onset nephrotic disease. Model: Human genetic disease study with functional analyses; GON7-associated cases were milder in the reported series. Limitations: This is an inherited machinery disorder, not demonstrated dietary threonine deficiency or a proven supplementation-responsive syndrome. Evidence access: Primary abstract Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31481669/ · DOI 10.1038/s41467-019-11951-x