L-Lysine

experimental_model

Recombinant human AASS and isolated reductase domain

limitations

Reaction reversibility in vitro does not imply appreciable human lysine biosynthesis.

organism

Homo sapiens

plain_language

AASS starts the main lysine breakdown route.

primary_references

[leandro2022] Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1 (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9490328/ DOI: 10.1098/rsob.220179

tissue_or_cell_type

Mitochondrial matrix

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human AASS and isolated reductase domain · source_derived_draft · unverified_draft

### aass-reductase The AASS reductase domain condenses lysine with 2-oxoglutarate using NADPH to form saccharopine. Plain language: AASS starts the main lysine breakdown route. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human AASS and isolated reductase domain limitations: Reaction reversibility in vitro does not imply appreciable human lysine biosynthesis. [leandro2022] Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1 (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9490328/ DOI: 10.1098/rsob.220179

experimental_model

Six-day randomized crossover feeding study in 14 women

limitations

Combined amino acids; small sample; specifically low-protein background diet; no long-term skeletal endpoint.

organism

Homo sapiens

plain_language

The trial did not establish a statistically significant absorption benefit.

primary_references

[bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009

tissue_or_cell_type

Intestine

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-day randomized crossover feeding study in 14 women · source_derived_draft · unverified_draft

### dibasic-calcium-absorption-trend Adding lysine plus arginine to a low-protein diet produced only a nonsignificant calcium-absorption trend: 25.2% versus 22.3% with control, P=0.094. Plain language: The trial did not establish a statistically significant absorption benefit. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Intestine experimental_model: Six-day randomized crossover feeding study in 14 women limitations: Combined amino acids; small sample; specifically low-protein background diet; no long-term skeletal endpoint. [bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009

experimental_model

Randomized crossover feeding trial in 14 women

limitations

No lysine-only arm or demonstrated long-term calcium-balance effect.

organism

Homo sapiens

plain_language

More urinary calcium accompanied the mixture; it cannot by itself be read as either bone loss or better bone health.

primary_references

[bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009

tissue_or_cell_type

Kidney and urine

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover feeding trial in 14 women · source_derived_draft · unverified_draft

### dibasic-urinary-calcium-increase In the same crossover study, lysine plus arginine significantly increased urinary calcium compared with the low-protein control diet. Plain language: More urinary calcium accompanied the mixture; it cannot by itself be read as either bone loss or better bone health. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney and urine experimental_model: Randomized crossover feeding trial in 14 women limitations: No lysine-only arm or demonstrated long-term calcium-balance effect. [bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Double-blind family feeding trial

limitations

Predominantly cereal-based, economically constrained diet; not proof of growth enhancement in lysine-replete children or isolated lysine deficiency in every participant.

organism

Homo sapiens

plain_language

Improving a lysine-poor staple was associated with better child growth in this dietary setting.

primary_references

[hussain2004] Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan (2004). https://pubmed.ncbi.nlm.nih.gov/15214256/ DOI: 10.1177/156482650402500202

tissue_or_cell_type

Whole-body growth

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind family feeding trial · source_derived_draft · unverified_draft

### fortification-child-growth In the Pakistani wheat-fortification trial, children receiving lysine-fortified flour gained more height and weight than controls over three months. Plain language: Improving a lysine-poor staple was associated with better child growth in this dietary setting. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Whole-body growth experimental_model: Double-blind family feeding trial limitations: Predominantly cereal-based, economically constrained diet; not proof of growth enhancement in lysine-replete children or isolated lysine deficiency in every participant. [hussain2004] Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan (2004). https://pubmed.ncbi.nlm.nih.gov/15214256/ DOI: 10.1177/156482650402500202

experimental_model

Randomized placebo-controlled community trial using 1 g/day

limitations

Only a subset was at estimated dietary inadequacy risk; within-group improvement does not show treatment efficacy.

organism

Homo sapiens

plain_language

Questionnaire anxiety improved in both groups, without a lysine-specific difference.

primary_references

[ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834

tissue_or_cell_type

Behavioral questionnaires and skin conductance

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled community trial using 1 g/day · source_derived_draft · unverified_draft

### ghana-anxiety-null The Ghana trial found no significant lysine-placebo difference in trait-anxiety change or skin-conductance stress responses. Plain language: Questionnaire anxiety improved in both groups, without a lysine-specific difference. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Behavioral questionnaires and skin conductance experimental_model: Randomized placebo-controlled community trial using 1 g/day limitations: Only a subset was at estimated dietary inadequacy risk; within-group improvement does not show treatment efficacy. [ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834

experimental_model

Randomized placebo-controlled community trial

limitations

Context-specific clinical result; does not establish receptor antagonism, intestinal repair mechanism, or broad infection prevention.

organism

Homo sapiens

plain_language

A benefit appeared for this child morbidity endpoint in the studied community.

primary_references

[ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834

tissue_or_cell_type

Gastrointestinal illness outcomes

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

### ghana-child-diarrhea In the Ghana trial, lysine supplementation was associated with fewer child diarrheal episodes and illness days than placebo. Plain language: A benefit appeared for this child morbidity endpoint in the studied community. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Gastrointestinal illness outcomes experimental_model: Randomized placebo-controlled community trial limitations: Context-specific clinical result; does not establish receptor antagonism, intestinal repair mechanism, or broad infection prevention. [ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834

experimental_model

Double-blind crossover clinical trial in 65 patients

limitations

Twelve-week treatment periods; outcome definition and regimen differ from the later positive trial.

organism

Homo sapiens

plain_language

The average recurrence and healing results were negative, although one secondary pattern favored treatment.

primary_references

[milman1980] Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. (1980). https://medicaljournalssweden.se/actadv/article/view/10630 DOI: 10.2340/00015555608587

tissue_or_cell_type

Lip herpes lesions

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover clinical trial in 65 patients · source_derived_draft · unverified_draft

### hsv-recurrence-null-trial The 1980 crossover trial found no overall reduction in herpes-labialis recurrence or healing time with 1 g daily lysine, despite more recurrence-free participants. Plain language: The average recurrence and healing results were negative, although one secondary pattern favored treatment. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Lip herpes lesions experimental_model: Double-blind crossover clinical trial in 65 patients limitations: Twelve-week treatment periods; outcome definition and regimen differ from the later positive trial. [milman1980] Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. (1980). https://medicaljournalssweden.se/actadv/article/view/10630 DOI: 10.2340/00015555608587

experimental_model

Double-blind placebo-controlled multicenter clinical trial

limitations

52 completers; reported symptom/healing findings do not prove direct viral inhibition; intake is a studied regimen, not a recommendation.

organism

Homo sapiens

plain_language

One small trial favored lysine for recurrence prevention.

primary_references

[griffith1987] Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. (1987). https://pubmed.ncbi.nlm.nih.gov/3115841/ DOI: 10.1159/000248823

tissue_or_cell_type

Clinical mucocutaneous HSV outcomes

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

### hsv-recurrence-positive-trial The 1987 trial reported fewer recurrent HSV episodes with lysine than placebo among completers receiving 1 g three times daily for six months. Plain language: One small trial favored lysine for recurrence prevention. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Clinical mucocutaneous HSV outcomes experimental_model: Double-blind placebo-controlled multicenter clinical trial limitations: 52 completers; reported symptom/healing findings do not prove direct viral inhibition; intake is a studied regimen, not a recommendation. [griffith1987] Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. (1987). https://pubmed.ncbi.nlm.nih.gov/3115841/ DOI: 10.1159/000248823

experimental_model

Human LysRS cryo-EM and aminoacylation assays

limitations

The structural experiment used tRNA-Lys3; KARS1 is not the leucyl-tRNA synthetase LARS1.

organism

Homo sapiens

plain_language

ATP activates lysine before it is attached to its carrier RNA.

primary_references

[devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114

tissue_or_cell_type

Cytosolic tRNA charging

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human LysRS cryo-EM and aminoacylation assays · source_derived_draft · unverified_draft

### lysine-adenylation KARS1 activates lysine with ATP, forming enzyme-bound lysyl-adenylate and releasing pyrophosphate. Plain language: ATP activates lysine before it is attached to its carrier RNA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic tRNA charging experimental_model: Human LysRS cryo-EM and aminoacylation assays limitations: The structural experiment used tRNA-Lys3; KARS1 is not the leucyl-tRNA synthetase LARS1. [devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114

experimental_model

Randomized double-blind placebo-controlled trial; 2.64 g/day of each amino acid

limitations

Short duration; no lysine-only arm; no established treatment effect for diagnosed anxiety disorders.

organism

Homo sapiens

plain_language

The tested mixture improved anxiety scores; the contribution of lysine alone is unknown.

primary_references

[smriga2007] Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans (2007). https://pubmed.ncbi.nlm.nih.gov/17510493/ DOI: 10.2220/biomedres.28.85

tissue_or_cell_type

Behavioral questionnaires

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial; 2.64 g/day of each amino acid · source_derived_draft · unverified_draft

### lysine-arginine-anxiety One week of combined lysine and arginine reduced trait and stress-induced state anxiety in a randomized trial of 108 healthy Japanese adults. Plain language: The tested mixture improved anxiety scores; the contribution of lysine alone is unknown. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Behavioral questionnaires experimental_model: Randomized double-blind placebo-controlled trial; 2.64 g/day of each amino acid limitations: Short duration; no lysine-only arm; no established treatment effect for diagnosed anxiety disorders. [smriga2007] Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans (2007). https://pubmed.ncbi.nlm.nih.gov/17510493/ DOI: 10.2220/biomedres.28.85

experimental_model

Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress

limitations

Small combination trial; authors' proposed normalization is an interpretation, not a proven lysine-specific mechanism.

organism

Homo sapiens

plain_language

The mixture did not simply suppress all stress hormones.

primary_references

[jezova2005] Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety (2005). https://pubmed.ncbi.nlm.nih.gov/16117182/ DOI: 10.1080/10284150500162937

tissue_or_cell_type

Blood stress hormones and cardiovascular measurements

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress · source_derived_draft · unverified_draft

### lysine-arginine-stress-hormones In 29 high-trait-anxiety participants, lysine plus arginine increased stress-evoked ACTH, cortisol, adrenaline, and noradrenaline responses without changing heart-rate or blood-pressure responses. Plain language: The mixture did not simply suppress all stress hormones. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Blood stress hormones and cardiovascular measurements experimental_model: Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress limitations: Small combination trial; authors' proposed normalization is an interpretation, not a proven lysine-specific mechanism. [jezova2005] Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety (2005). https://pubmed.ncbi.nlm.nih.gov/16117182/ DOI: 10.1080/10284150500162937

experimental_model

Amino-acid comparator experiment using 800 mg/day in 45 osteoporotic patients

limitations

Short-term mineral handling; no fracture prevention or bone-density benefit established.

organism

Homo sapiens

plain_language

A small experiment found better absorption of calcium.

primary_references

[civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/

tissue_or_cell_type

Intestine

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Amino-acid comparator experiment using 800 mg/day in 45 osteoporotic patients · source_derived_draft · unverified_draft

### lysine-calcium-intestinal-study In a short-term study of osteoporotic patients, lysine supplementation increased measured calcium absorption, whereas the valine and tryptophan comparators did not. Plain language: A small experiment found better absorption of calcium. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Intestine experimental_model: Amino-acid comparator experiment using 800 mg/day in 45 osteoporotic patients limitations: Short-term mineral handling; no fracture prevention or bone-density benefit established. [civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/

experimental_model

Acute calcium-load comparison; healthy and osteoporotic women

limitations

Acute load response does not establish long-term calcium balance or skeletal outcomes.

organism

Homo sapiens

plain_language

Lysine altered short-term urinary calcium handling in one subgroup.

primary_references

[civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/

tissue_or_cell_type

Kidney and urine

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute calcium-load comparison; healthy and osteoporotic women · source_derived_draft · unverified_draft

### lysine-calcium-urinary-blunting In healthy women, adding 400 mg lysine to a calcium load blunted the subsequent rise in urinary calcium; this pattern was not reported for the osteoporotic group. Plain language: Lysine altered short-term urinary calcium handling in one subgroup. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney and urine experimental_model: Acute calcium-load comparison; healthy and osteoporotic women limitations: Acute load response does not establish long-term calcium balance or skeletal outcomes. [civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Live-cell imaging and perturbation experiments, primarily MCF10A and RPE-hTERT

limitations

Cell-line and acute-starvation context; response differs among amino acids and may vary across primary tissues.

organism

Homo sapiens

plain_language

Removing this required amino acid disrupted protein production and division in cultured cells.

primary_references

[rong2023] Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC11238304/ DOI: 10.1016/j.celrep.2023.113539

tissue_or_cell_type

Mammary epithelial and retinal pigment epithelial cell lines

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Live-cell imaging and perturbation experiments, primarily MCF10A and RPE-hTERT · source_derived_draft · unverified_draft

### lysine-deprivation-cellcycle In noncancerous human cell lines, lysine withdrawal rapidly inhibited protein synthesis and stalled cell-cycle progression. Plain language: Removing this required amino acid disrupted protein production and division in cultured cells. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Mammary epithelial and retinal pigment epithelial cell lines experimental_model: Live-cell imaging and perturbation experiments, primarily MCF10A and RPE-hTERT limitations: Cell-line and acute-starvation context; response differs among amino acids and may vary across primary tissues. [rong2023] Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC11238304/ DOI: 10.1016/j.celrep.2023.113539

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Human NSCLC cell cultures including H1299, H460, and A549

limitations

Abrupt medium depletion; no direct lysine-binding sensor established; no supplementation benefit inferred for healthy humans.

organism

Homo sapiens

plain_language

These cultured cancer cells needed available lysine for full nutrient-and-growth-factor signaling.

primary_references

[jang2020] Lysine is required for growth factor-induced mTORC1 activation (2020). https://pubmed.ncbi.nlm.nih.gov/33008594/ DOI: 10.1016/j.bbrc.2020.09.100

tissue_or_cell_type

Cultured lung cancer cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NSCLC cell cultures including H1299, H460, and A549 · source_derived_draft · unverified_draft

### lysine-deprivation-mtorc1 Lysine withdrawal suppressed mTORC1 activity in NSCLC cell lines, and lysine restoration reversed the suppression; GCN2 and AMPK contributed to this response. Plain language: These cultured cancer cells needed available lysine for full nutrient-and-growth-factor signaling. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Cultured lung cancer cells experimental_model: Human NSCLC cell cultures including H1299, H460, and A549 limitations: Abrupt medium depletion; no direct lysine-binding sensor established; no supplementation benefit inferred for healthy humans. [jang2020] Lysine is required for growth factor-induced mTORC1 activation (2020). https://pubmed.ncbi.nlm.nih.gov/33008594/ DOI: 10.1016/j.bbrc.2020.09.100

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Controlled isotope feeding experiment

limitations

Small male sample; surrogate measure; plateau is not evidence that extra lysine beyond adequacy builds more muscle.

organism

Homo sapiens

plain_language

When lysine was limiting, less of another amino acid was retained; providing more lysine changed that metabolic readout up to a plateau.

primary_references

[zello1993] Dietary lysine requirement of young adult males determined by oxidation of L-[1-13C]phenylalanine (1993). https://pubmed.ncbi.nlm.nih.gov/8476044/ DOI: 10.1152/ajpendo.1993.264.4.E677

tissue_or_cell_type

Whole-body amino-acid metabolism

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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

### lysine-intake-indicator-oxidation In seven men receiving graded lysine intakes, indicator phenylalanine oxidation fell until a breakpoint and then remained approximately constant. Plain language: When lysine was limiting, less of another amino acid was retained; providing more lysine changed that metabolic readout up to a plateau. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Whole-body amino-acid metabolism experimental_model: Controlled isotope feeding experiment limitations: Small male sample; surrogate measure; plateau is not evidence that extra lysine beyond adequacy builds more muscle. [zello1993] Dietary lysine requirement of young adult males determined by oxidation of L-[1-13C]phenylalanine (1993). https://pubmed.ncbi.nlm.nih.gov/8476044/ DOI: 10.1152/ajpendo.1993.264.4.E677

experimental_model

Single clinical case report

limitations

No controlled comparison; susceptible individuals, coexposures, causality, and incidence cannot be resolved from this report.

organism

Homo sapiens

plain_language

This is a safety signal from one patient, not an established frequency or proof of cause.

primary_references

[lo1996] Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion (1996). https://pubmed.ncbi.nlm.nih.gov/8840955/ DOI: 10.1016/s0272-6386(96)90476-x

tissue_or_cell_type

Renal tubules and interstitium

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

### lysine-renal-case-association A single case report associated oral lysine ingestion with Fanconi syndrome, severe tubulointerstitial nephritis, and subsequent chronic renal failure. Plain language: This is a safety signal from one patient, not an established frequency or proof of cause. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Renal tubules and interstitium experimental_model: Single clinical case report limitations: No controlled comparison; susceptible individuals, coexposures, causality, and incidence cannot be resolved from this report. [lo1996] Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion (1996). https://pubmed.ncbi.nlm.nih.gov/8840955/ DOI: 10.1016/s0272-6386(96)90476-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Randomized household fortification trial

limitations

Prestress baseline cortisol was not measured; not evidence of universal cortisol lowering.

organism

Homo sapiens

plain_language

The measured response to a specific stressor differed by sex.

primary_references

[smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101

tissue_or_cell_type

Blood cortisol under venipuncture stress

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

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

### syria-stress-cortisol In the Syrian trial, lysine fortification reduced the cortisol response associated with blood drawing in females, without the same effect in males. Plain language: The measured response to a specific stressor differed by sex. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Blood cortisol under venipuncture stress experimental_model: Randomized household fortification trial limitations: Prestress baseline cortisol was not measured; not evidence of universal cortisol lowering. [smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Three-month randomized household trial

limitations

Dietary estimates, not individual biochemical diagnosis; one questionnaire; cannot establish treatment of anxiety disorders.

organism

Homo sapiens

plain_language

The anxiety result was subgroup-specific in a population with probable dietary inadequacy.

primary_references

[smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101

tissue_or_cell_type

Behavioral questionnaire outcome

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 689–697

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-month randomized household trial · source_derived_draft · unverified_draft

### syria-trait-anxiety Syrian wheat fortification reduced trait-anxiety scores in men, with benefit concentrated in those with high baseline anxiety; women showed no trait-anxiety effect. Plain language: The anxiety result was subgroup-specific in a population with probable dietary inadequacy. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Behavioral questionnaire outcome experimental_model: Three-month randomized household trial limitations: Dietary estimates, not individual biochemical diagnosis; one questionnaire; cannot establish treatment of anxiety disorders. [smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101

experimental_model

Randomized intake-order repeated-measures experiment in five young men

exposure

Lysine supplied by the tested whole-wheat bread; bread is a food matrix recorded in context, not a chemical-species entity.

limitations

Specific bread and small sample; metabolic availability is method-dependent and does not establish adequacy of all wheat-based diets.

organism

Homo sapiens

plain_language

A food can deliver most of its lysine efficiently yet contain too little lysine relative to other amino acids.

primary_references

[tulnoor2025] Lysine from Whole Wheat Bread Consumed by Healthy Adult Males Has High Metabolic Availability When Assessed Using the Indicator Amino Acid Oxidation Method (2025). https://pubmed.ncbi.nlm.nih.gov/39163973/ DOI: 10.1016/j.tjnut.2024.08.011

tissue_or_cell_type

Whole-body amino-acid metabolism

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 648–657

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized intake-order repeated-measures experiment in five young men · source_derived_draft · unverified_draft

### wholewheat-lysine-availability The tested whole-wheat bread supplied lysine with an estimated 90% metabolic availability, while low lysine concentration still limited its protein quality. Plain language: A food can deliver most of its lysine efficiently yet contain too little lysine relative to other amino acids. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Whole-body amino-acid metabolism experimental_model: Randomized intake-order repeated-measures experiment in five young men limitations: Specific bread and small sample; metabolic availability is method-dependent and does not establish adequacy of all wheat-based diets. exposure: Lysine supplied by the tested whole-wheat bread; bread is a food matrix recorded in context, not a chemical-species entity. [tulnoor2025] Lysine from Whole Wheat Bread Consumed by Healthy Adult Males Has High Metabolic Availability When Assessed Using the Indicator Amino Acid Oxidation Method (2025). https://pubmed.ncbi.nlm.nih.gov/39163973/ DOI: 10.1016/j.tjnut.2024.08.011

experimental_model

Human/mouse cloning, Xenopus transport and renal localization

limitations

Leucine is an example exchange substrate, not the obligatory unique counter-substrate.

organism

Human and mouse proteins; Xenopus expression system

plain_language

This transporter admits lysine at the gut or kidney lumen-facing surface.

primary_references

[pfeiffer1999b0] Luminal Heterodimeric Amino Acid Transporter Defective in Cystinuria (1999). https://pmc.ncbi.nlm.nih.gov/articles/PMC25748/ DOI: 10.1091/mbc.10.12.4135

tissue_or_cell_type

Renal proximal-tubule brush border; intestinal apical context

transport_effect

depends The record names sodium-independent lysine exchange and not which way lysine moves in it.

transport_pool

the enterocyte interior across the apical membrane The record names sodium-independent lysine exchange and not which way lysine moves in it.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 24–32

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human/mouse cloning, Xenopus transport and renal localization · source_derived_draft · unverified_draft

### apical-lysine-exchange SLC7A9 associated with SLC3A1 mediates sodium-independent lysine exchange at the apical epithelial membrane. Plain language: This transporter admits lysine at the gut or kidney lumen-facing surface. Condition category: normal organism: Human and mouse proteins; Xenopus expression system tissue_or_cell_type: Renal proximal-tubule brush border; intestinal apical context experimental_model: Human/mouse cloning, Xenopus transport and renal localization limitations: Leucine is an example exchange substrate, not the obligatory unique counter-substrate. [pfeiffer1999b0] Luminal Heterodimeric Amino Acid Transporter Defective in Cystinuria (1999). https://pmc.ncbi.nlm.nih.gov/articles/PMC25748/ DOI: 10.1091/mbc.10.12.4135

experimental_model

E. coli inducible lysine decarboxylase structural and acid-stress experiments.

limitations

Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism.

organism

Escherichia coli

plain_language

Some bacteria use lysine to buffer acidic conditions.

primary_references

[cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 618–626

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · E. coli inducible lysine decarboxylase structural and acid-stress experiments. · source_derived_draft · unverified_draft

### bacterial-cada-decarboxylation E. coli CadA converts lysine to cadaverine and CO2 while consuming a proton during acid stress. Plain language: Some bacteria use lysine to buffer acidic conditions. Condition category: normal organism: Escherichia coli tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: E. coli inducible lysine decarboxylase structural and acid-stress experiments. limitations: Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism. [cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

experimental_model

Human/mouse heterodimer expression and exchange assays

limitations

Neutral-substrate transport is sodium-dependent; lysine binding itself should not be mislabeled a sodium cotransport step.

organism

Homo sapiens

plain_language

This route helps lysine leave epithelial cells toward blood.

primary_references

[pfeiffer1999yl] Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family. (1999). https://pubmed.ncbi.nlm.nih.gov/9878049/ DOI: 10.1093/emboj/18.1.49

tissue_or_cell_type

Basolateral intestinal and renal epithelial membranes

transport_effect

lowers Exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids, so lysine leaves the cell.

transport_pool

the enterocyte interior Exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids, so lysine leaves the cell.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 34–42

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human/mouse heterodimer expression and exchange assays · source_derived_draft · unverified_draft

### basolateral-lysine-exchange SLC7A7-SLC3A2 exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids with sodium. Plain language: This route helps lysine leave epithelial cells toward blood. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Basolateral intestinal and renal epithelial membranes experimental_model: Human/mouse heterodimer expression and exchange assays limitations: Neutral-substrate transport is sodium-dependent; lysine binding itself should not be mislabeled a sodium cotransport step. [pfeiffer1999yl] Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family. (1999). https://pubmed.ncbi.nlm.nih.gov/9878049/ DOI: 10.1093/emboj/18.1.49

experimental_model

Human CAT1 expressed in Xenopus oocytes

limitations

Transporter expression assay; the relative contribution varies by tissue.

organism

Homo sapiens

plain_language

CAT1 moves free lysine across cell membranes.

primary_references

[furesz2002] Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast surface membranes. (2002). https://pubmed.ncbi.nlm.nih.gov/12202949/ DOI: 10.1007/s00232-002-1001-0

tissue_or_cell_type

Plasma membrane; compared with placental trophoblast membranes

transport_effect

depends The record names the membrane lysine crosses and not which way it crosses it.

transport_pool

the cytosol across the plasma membrane The record names the membrane lysine crosses and not which way it crosses it.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 14–22

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CAT1 expressed in Xenopus oocytes · source_derived_draft · unverified_draft

### cat1-lysine-transport Human CAT1 transports L-lysine across the plasma membrane. Plain language: CAT1 moves free lysine across cell membranes. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Plasma membrane; compared with placental trophoblast membranes experimental_model: Human CAT1 expressed in Xenopus oocytes limitations: Transporter expression assay; the relative contribution varies by tissue. [furesz2002] Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast surface membranes. (2002). https://pubmed.ncbi.nlm.nih.gov/12202949/ DOI: 10.1007/s00232-002-1001-0

experimental_model

Purified recombinant carrier reconstituted in liposomes

limitations

Physiological import role is inferred from transport properties and localization; not a carnitine transporter.

organism

Homo sapiens

plain_language

SLC25A29 gives lysine access to mitochondrial metabolism.

primary_references

[porcelli2014] The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4036346/ DOI: 10.1074/jbc.M114.547448

tissue_or_cell_type

Inner mitochondrial membrane

transport_effect

raises Uniport and exchange supporting lysine entry into the matrix.

transport_pool

the mitochondrial matrix Uniport and exchange supporting lysine entry into the matrix.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 44–52

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant carrier reconstituted in liposomes · source_derived_draft · unverified_draft

### mitochondrial-lysine-transport Reconstituted human SLC25A29 transports lysine by uniport and exchange, supporting lysine entry into the mitochondrial matrix. Plain language: SLC25A29 gives lysine access to mitochondrial metabolism. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Purified recombinant carrier reconstituted in liposomes limitations: Physiological import role is inferred from transport properties and localization; not a carnitine transporter. [porcelli2014] The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4036346/ DOI: 10.1074/jbc.M114.547448

evidence_span

{"source_cache": "artifacts/biotin-research/6883721.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f881dd651d45537377661fc515239c3babb7160c3dbd53b8b0611ba33625aaa", "start_char": 0, "end_char": 1500, "text_sha256": "0f881dd651d45537377661fc515239c3babb7160c3dbd53b8b0611ba33625aaa"}

experimental_model

Serum enzyme assays in 5 children with late-onset multiple carboxylase deficiency and family members

exposure

Inherited deficiency; patient/control comparison

limitations

Early small case series; the serum enzyme phenotype is genetic machinery impairment, not proof of low dietary intake.

nutrient_topic

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

organism

Homo sapiens

plain_language

Biotinidase recovers biotin after biotin-containing material is broken down.

primary_references

[b7-p6883721] Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. (1983). https://pubmed.ncbi.nlm.nih.gov/6883721/ DOI: 10.1016/0009-8981(83)90096-7

tissue_or_cell_type

Serum and biochemical disease phenotype

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 455–466

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Serum enzyme assays in 5 children with late-onset multiple carboxylase deficiency and family members · source_derived_draft · unverified_draft

### b7-btd-recycling Biotinidase releases biotin from its linkage to the epsilon-amino group of lysine, allowing the cofactor to be reused. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotinidase recovers biotin after biotin-containing material is broken down. organism: Homo sapiens tissue_or_cell_type: Serum and biochemical disease phenotype experimental_model: Serum enzyme assays in 5 children with late-onset multiple carboxylase deficiency and family members limitations: Early small case series; the serum enzyme phenotype is genetic machinery impairment, not proof of low dietary intake. exposure: Inherited deficiency; patient/control comparison evidence_span: {"source_cache": "artifacts/biotin-research/6883721.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f881dd651d45537377661fc515239c3babb7160c3dbd53b8b0611ba33625aaa", "start_char": 0, "end_char": 1500, "text_sha256": "0f881dd651d45537377661fc515239c3babb7160c3dbd53b8b0611ba33625aaa"} [b7-p6883721] Biotinidase deficiency: the enzymatic defect in late-onset multiple carboxylase deficiency. (1983). https://pubmed.ncbi.nlm.nih.gov/6883721/ DOI: 10.1016/0009-8981(83)90096-7

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Lysine catabolism generates the metabolite that can sequester PLP.

experimental_model

Affected children, expressed human ALDH7A1 variants and metabolite chemistry

exposure

ALDH7A1-associated disease and metabolite analysis.

limitations

This is inherited pathway failure, not lysine toxicity in healthy people.

nutrient_topic

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

organism

Homo sapiens

plain_language

A blocked lysine pathway builds up B6-reactive metabolites.

primary_references

[mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366

tissue_or_cell_type

Patient biological samples and biochemical pathway analysis

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1158–1169

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected children, expressed human ALDH7A1 variants and metabolite chemistry · source_derived_draft · unverified_draft

### b6-neuro-aldh7a1-metabolite-accumulation The antiquitin defect was linked to accumulation of alpha-AASA/P6C in the lysine degradation pathway. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blocked lysine pathway builds up B6-reactive metabolites. organism: Homo sapiens tissue_or_cell_type: Patient biological samples and biochemical pathway analysis experimental_model: Affected children, expressed human ALDH7A1 variants and metabolite chemistry limitations: This is inherited pathway failure, not lysine toxicity in healthy people. exposure: ALDH7A1-associated disease and metabolite analysis. cross_nutrient: Lysine catabolism generates the metabolite that can sequester PLP. [mills-2006-aldh7a1] Mutations in antiquitin in individuals with pyridoxine-dependent seizures (2006). https://doi.org/10.1038/nm1366 DOI: 10.1038/nm1366

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

A B1-dependent enzyme connects lysine degradation to glutaryl-CoA metabolism.

evidence

[{"paper_key": "danhauser-2012-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Patient fibroblasts, isotope tracing and lentiviral complementation.

limitations

Two individuals; neurological phenotypes vary and biochemical rescue does not prove a clinical treatment.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Replacing the faulty enzyme restored the tested metabolic step. The experiment identifies a machinery defect rather than a lack of dietary B1.

primary_references

[danhauser-2012-dhtkd1] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pubmed.ncbi.nlm.nih.gov/23141293/ DOI: 10.1016/j.ajhg.2012.10.006

tissue_or_cell_type

Cultured fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 909–921

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

### b1-dhtkd1-patient-lysine-turnover Patient DHTKD1-deficient fibroblasts accumulated deuterium-labeled 2-oxoadipate from labeled lysine; wild-type DHTKD1 expression normalized the biochemical defect. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the faulty enzyme restored the tested metabolic step. The experiment identifies a machinery defect rather than a lack of dietary B1. organism: Homo sapiens tissue_or_cell_type: Cultured fibroblasts experimental_model: Patient fibroblasts, isotope tracing and lentiviral complementation. limitations: Two individuals; neurological phenotypes vary and biochemical rescue does not prove a clinical treatment. evidence: [{"paper_key": "danhauser-2012-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: A B1-dependent enzyme connects lysine degradation to glutaryl-CoA metabolism. nutrient: Thiamine (vitamin B1) [danhauser-2012-dhtkd1] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pubmed.ncbi.nlm.nih.gov/23141293/ DOI: 10.1016/j.ajhg.2012.10.006

cross_nutrient

B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH.

evidence

[{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human recombinant component reconstitution.

limitations

Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme.

primary_references

[nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

tissue_or_cell_type

Purified complex

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 869–881

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

### b1-dhtkd1-recruits-shared-dlst-dld Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme. organism: Homo sapiens tissue_or_cell_type: Purified complex experimental_model: Human recombinant component reconstitution. limitations: Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH. nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

cross_nutrient

Amino-acid catabolism and central carbon metabolism communicate through an acyl-CoA product.

evidence

[{"paper_key": "nemeria-2018-crosstalk", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Reconstituted human enzyme inhibition assays.

limitations

In vitro regulation; physiological free metabolite concentrations and net in vivo effect were not established.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

A product of one B1-dependent route can restrain a different B1 enzyme in a test tube. Its importance inside tissues remains unquantified.

primary_references

[nemeria-2018-crosstalk] Evidence for functional and regulatory cross-talk between the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex and 2-oxoadipate dehydrogenase on the l-lysine, l-hydroxylysine and l-tryptophan degradation pathways from studies in vitro (2018). https://pubmed.ncbi.nlm.nih.gov/29752936/ DOI: 10.1016/j.bbabio.2018.05.001

tissue_or_cell_type

Purified complexes

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 936–948

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

### b1-lysine-product-inhibits-ogdh Glutaryl-CoA inhibited human OGDH activity in reconstituted experiments, supporting possible regulatory communication from OADH-linked amino-acid degradation to the TCA cycle. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A product of one B1-dependent route can restrain a different B1 enzyme in a test tube. Its importance inside tissues remains unquantified. organism: Homo sapiens tissue_or_cell_type: Purified complexes experimental_model: Reconstituted human enzyme inhibition assays. limitations: In vitro regulation; physiological free metabolite concentrations and net in vivo effect were not established. evidence: [{"paper_key": "nemeria-2018-crosstalk", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Amino-acid catabolism and central carbon metabolism communicate through an acyl-CoA product. nutrient: Thiamine (vitamin B1) [nemeria-2018-crosstalk] Evidence for functional and regulatory cross-talk between the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex and 2-oxoadipate dehydrogenase on the l-lysine, l-hydroxylysine and l-tryptophan degradation pathways from studies in vitro (2018). https://pubmed.ncbi.nlm.nih.gov/29752936/ DOI: 10.1016/j.bbabio.2018.05.001

evidence_access

Primary full text

experimental_model

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

limitations

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

nutrient_topic

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

plain_language

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

primary_references

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

Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 402–408

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bovine articular chondrocyte monolayers; 15-day concentration series and collagen ELISA. · source_derived_draft · unverified_draft

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Gcn2-deficient mice crossed to TCR-transgenic backgrounds; defined amino-acid limitation.

limitations

Not identical to every IDO-dendritic-cell preparation; the authors explicitly challenge the earlier necessity model.

nutrient_topic

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

plain_language

Another study found the division block persisted without that sensor.

primary_references

Stress Kinase GCN2 Controls the Proliferative Fitness and Trafficking of Cytotoxic T Cells Independent of Environmental Amino Acid Sensing. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27880901/ · DOI 10.1016/j.celrep.2016.10.079

trigger_kind

machinery_impairment Imported condition classification; unverified.

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 378–384

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Gcn2-deficient mice crossed to TCR-transgenic backgrounds; defined amino-acid limitation. · source_derived_draft · unverified_draft

## tryptophan-gcn2-not-required Another study found the division block persisted without that sensor. GCN2-deficient mouse CD8 T cells still failed to proliferate under limiting tryptophan, arginine, leucine, lysine or asparagine in the 2016 study. Model: Gcn2-deficient mice crossed to TCR-transgenic backgrounds; defined amino-acid limitation. Limitations: Not identical to every IDO-dendritic-cell preparation; the authors explicitly challenge the earlier necessity model. Evidence access: Primary abstract Stress Kinase GCN2 Controls the Proliferative Fitness and Trafficking of Cytotoxic T Cells Independent of Environmental Amino Acid Sensing. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27880901/ · DOI 10.1016/j.celrep.2016.10.079

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

evidence_access

Primary full text

experimental_model

Human transporter cryo-EM and functional study; structural ligand was arginine.

limitations

Do not describe the arginine-bound structure as a captured cystine-bound state or infer dietary competition from binding alone.

nutrient_topic

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

plain_language

The kidney and intestine use a two-protein exchange system to handle cystine.

primary_references

Cryo-EM structure of the human heteromeric amino acid transporter b0,+AT-rBAT. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32494597/ · DOI 10.1126/sciadv.aay6379

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 20–26

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter cryo-EM and functional study; structural ligand was arginine. · source_derived_draft · unverified_draft

## l-cysteine-renal-cystine-exchange The kidney and intestine use a two-protein exchange system to handle cystine. Human SLC7A9 and SLC3A1 form the b0,+AT–rBAT obligatory exchanger for cystine/cationic amino-acid influx coupled to neutral amino-acid efflux. Model: Human transporter cryo-EM and functional study; structural ligand was arginine. Limitations: Do not describe the arginine-bound structure as a captured cystine-bound state or infer dietary competition from binding alone. Evidence access: Primary full text Cryo-EM structure of the human heteromeric amino acid transporter b0,+AT-rBAT. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32494597/ · DOI 10.1126/sciadv.aay6379

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/6776014.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d", "start_char": 0, "end_char": 1189, "text_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d"}

experimental_model

Oral amino-acid loading comparison

exposure

Separate diamino-acid and citrulline loads

limitations

Inherited transport disorder, not ordinary competition from mixed dietary protein; the study predates gene identification.

nutrient_topic

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

organism

Human LPI patients, heterozygotes and controls

plain_language

A different entry route can bypass this particular transport problem.

primary_references

[citrulline-p6776014] Intestinal absorption in lysinuric protein intolerance: impaired for diamino acids, normal for citrulline. (1980). https://pubmed.ncbi.nlm.nih.gov/6776014/ DOI: 10.1136/gut.21.6.519

tissue_or_cell_type

Intestinal amino-acid absorption inferred from plasma and urine

trigger_kind

machinery_impairment Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 840–851

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral amino-acid loading comparison · source_derived_draft · unverified_draft

### citrulline-lpi-citrulline-absorption Citrulline plasma increments after oral loads were similar in LPI homozygotes and controls, unlike diamino-acid increments. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different entry route can bypass this particular transport problem. organism: Human LPI patients, heterozygotes and controls tissue_or_cell_type: Intestinal amino-acid absorption inferred from plasma and urine experimental_model: Oral amino-acid loading comparison limitations: Inherited transport disorder, not ordinary competition from mixed dietary protein; the study predates gene identification. exposure: Separate diamino-acid and citrulline loads evidence_span: {"source_cache": "artifacts/citrulline-research/6776014.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d", "start_char": 0, "end_char": 1189, "text_sha256": "6db6a42e66322b8ae26335a4f51284ede7691dcbb91e8cf7d7cd6671bd41b87d"} [citrulline-p6776014] Intestinal absorption in lysinuric protein intolerance: impaired for diamino acids, normal for citrulline. (1980). https://pubmed.ncbi.nlm.nih.gov/6776014/ DOI: 10.1136/gut.21.6.519

evidence_access

Primary abstract

experimental_model

Cell-free lysine-MG AGE preparation.

limitations

The study does not demonstrate removal of established tissue AGE deposits.

nutrient_topic

Carnosine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnosine / beta-alanyl-L-histidine

plain_language

Protection was tested against secondary reaction products too.

primary_references

Carnosine protects proteins against methylglyoxal-mediated modifications. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9675080/ · DOI 10.1006/bbrc.1998.8806

Carnosine: synthesis, transport, carbonyl chemistry and nutrient interactions (2026-09-19) · lines 260–266

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cell-free lysine-MG AGE preparation. · source_derived_draft · unverified_draft

## carnosine-mg-secondary Protection was tested against secondary reaction products too. Carnosine also inhibited protein modification caused by products formed by incubating lysine with methylglyoxal. Model: Cell-free lysine-MG AGE preparation. Limitations: The study does not demonstrate removal of established tissue AGE deposits. Evidence access: Primary abstract Carnosine protects proteins against methylglyoxal-mediated modifications. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9675080/ · DOI 10.1006/bbrc.1998.8806

affected_machinery

AASS saccharopine dehydrogenase

availability_state

machinery_impairment Imported condition classification; unverified.

deficiency_not_equivalent

Dietary lysine deficiency or complete AASS knockout

experimental_model

AASS-domain mutant worms and engineered mice

limitations

Selective downstream-domain failure differs from complete AASS loss.

organism

Caenorhabditis elegans and Mus musculus

plain_language

Saccharopine builds up when its production continues but its removal fails.

primary_references

[zhou2019] The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6363459/ DOI: 10.1083/jcb.201807204

tissue_or_cell_type

Worm hypodermis and mouse liver

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 230–240

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AASS-domain mutant worms and engineered mice · source_derived_draft · unverified_draft

### aass-sdh-saccharopine-accumulation Selective AASS saccharopine-dehydrogenase impairment while reductase activity persists causes saccharopine accumulation. Plain language: Saccharopine builds up when its production continues but its removal fails. Condition category: machinery_impairment organism: Caenorhabditis elegans and Mus musculus tissue_or_cell_type: Worm hypodermis and mouse liver experimental_model: AASS-domain mutant worms and engineered mice limitations: Selective downstream-domain failure differs from complete AASS loss. affected_machinery: AASS saccharopine dehydrogenase deficiency_not_equivalent: Dietary lysine deficiency or complete AASS knockout [zhou2019] The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6363459/ DOI: 10.1083/jcb.201807204

experimental_model

E. coli cells and membrane vesicles expressing CadB; cadaverine uptake/excretion and lysine exchange assays.

limitations

Bacterial antiport, not the mammalian intestinal lysine transporter or a clinical dysbiosis claim.

organism

Escherichia coli

plain_language

Transport connects extracellular lysine with bacterial cadaverine release.

primary_references

[cadb-2004] Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli (2004). https://pubmed.ncbi.nlm.nih.gov/14982633/ DOI: 10.1046/j.1365-2958.2003.03913.x

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 628–636

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · E. coli cells and membrane vesicles expressing CadB; cadaverine uptake/excretion and lysine exchange assays. · source_derived_draft · unverified_draft

### bacterial-cadb-exchange E. coli CadB couples lysine uptake to cadaverine export in the Cad acid-response system. Plain language: Transport connects extracellular lysine with bacterial cadaverine release. Condition category: normal organism: Escherichia coli tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: E. coli cells and membrane vesicles expressing CadB; cadaverine uptake/excretion and lysine exchange assays. limitations: Bacterial antiport, not the mammalian intestinal lysine transporter or a clinical dysbiosis claim. [cadb-2004] Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli (2004). https://pubmed.ncbi.nlm.nih.gov/14982633/ DOI: 10.1046/j.1365-2958.2003.03913.x

affected_machinery

Oxoadipate-dehydrogenase E1

availability_state

machinery_impairment Imported condition classification; unverified.

deficiency_not_equivalent

Dietary lysine deficiency

experimental_model

Two human patients and isotope-traced fibroblasts

limitations

Biochemical causation is stronger than attribution of every neurological finding.

organism

Homo sapiens

plain_language

A downstream enzyme defect leaves oxoadipate uncleared.

primary_references

[danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

tissue_or_cell_type

Fibroblasts; clinical aciduria

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 278–288

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human patients and isotope-traced fibroblasts · source_derived_draft · unverified_draft

### dhtkd1-oxoadipate-accumulation DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal. Plain language: A downstream enzyme defect leaves oxoadipate uncleared. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Fibroblasts; clinical aciduria experimental_model: Two human patients and isotope-traced fibroblasts limitations: Biochemical causation is stronger than attribution of every neurological finding. affected_machinery: Oxoadipate-dehydrogenase E1 deficiency_not_equivalent: Dietary lysine deficiency [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

affected_machinery

GCDH

availability_state

machinery_impairment Imported condition classification; unverified.

deficiency_not_equivalent

Nutrient deficiency or normal human lysine intake

experimental_model

High-lysine dietary challenge of Gcdh-knockout mice

limitations

Genetic susceptibility and age are essential; does not show comparable toxicity in healthy humans.

organism

Mus musculus

plain_language

Lysine loading can worsen a blocked breakdown pathway.

primary_references

[zinnanti2006] A diet-induced mouse model for glutaric aciduria type I (2006). https://pubmed.ncbi.nlm.nih.gov/16446282/ DOI: 10.1093/brain/awl009

tissue_or_cell_type

Brain and systemic circulation

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 290–300

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-lysine dietary challenge of Gcdh-knockout mice · source_derived_draft · unverified_draft

### gcdh-high-lysine-glutarate High lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury. Plain language: Lysine loading can worsen a blocked breakdown pathway. Condition category: machinery_impairment organism: Mus musculus tissue_or_cell_type: Brain and systemic circulation experimental_model: High-lysine dietary challenge of Gcdh-knockout mice limitations: Genetic susceptibility and age are essential; does not show comparable toxicity in healthy humans. affected_machinery: GCDH deficiency_not_equivalent: Nutrient deficiency or normal human lysine intake [zinnanti2006] A diet-induced mouse model for glutaric aciduria type I (2006). https://pubmed.ncbi.nlm.nih.gov/16446282/ DOI: 10.1093/brain/awl009

experimental_model

Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo

limitations

Both protein arms included 2 g free leucine. Processing-related protein modification was manipulated; this was not a free-lysine supplementation or anti-glycation treatment trial.

organism

Homo sapiens

plain_language

Chemical modification of food protein changed how much lysine appeared in circulation.

primary_references

[vanlieshout2025] Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12308134/ DOI: 10.1016/j.tjnut.2025.05.032

tissue_or_cell_type

Blood after feeding

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 799–807

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo · source_derived_draft · unverified_draft

### milk-glycation-lysine-availability After resistance exercise, 20 g highly glycated milk protein yielded lower six-hour plasma lysine availability than less glycated protein in young men; both protein arms also received 2 g free leucine. Plain language: Chemical modification of food protein changed how much lysine appeared in circulation. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Blood after feeding experimental_model: Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo limitations: Both protein arms included 2 g free leucine. Processing-related protein modification was manipulated; this was not a free-lysine supplementation or anti-glycation treatment trial. [vanlieshout2025] Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12308134/ DOI: 10.1016/j.tjnut.2025.05.032

affected_machinery

SLC7A7-containing transporter

availability_state

machinery_impairment Imported condition classification; unverified.

deficiency_not_equivalent

Dietary lysine deficiency

experimental_model

Human inherited disease genetics and transport characterization

limitations

A multiamino-acid transport disorder; systemic manifestations are not attributable solely to dietary lysine shortage.

organism

Homo sapiens

plain_language

A transport defect can limit lysine delivery despite its presence in food.

primary_references

[torrents1999] Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene (1999). https://www.nature.com/articles/ng0399_293 DOI: 10.1038/6809

tissue_or_cell_type

Intestinal and renal epithelial basolateral membranes

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 218–228

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human inherited disease genetics and transport characterization · source_derived_draft · unverified_draft

### slc7a7-lpi Pathogenic SLC7A7 variants impair epithelial dibasic-amino-acid transport in lysinuric protein intolerance. Plain language: A transport defect can limit lysine delivery despite its presence in food. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Intestinal and renal epithelial basolateral membranes experimental_model: Human inherited disease genetics and transport characterization limitations: A multiamino-acid transport disorder; systemic manifestations are not attributable solely to dietary lysine shortage. affected_machinery: SLC7A7-containing transporter deficiency_not_equivalent: Dietary lysine deficiency [torrents1999] Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene (1999). https://www.nature.com/articles/ng0399_293 DOI: 10.1038/6809

evidence_access

Primary abstract

experimental_model

Nine men in oral lysine tests; three men in intravenous amino-acid loading tests.

limitations

Small historical experiment; no molecular transporter identified and no ordinary-meal effect size established.

nutrient_topic

L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine

plain_language

Related amino acids interacted at a kidney transport step.

primary_references

A new transport interaction of dibasic amino acids and citrulline in human kidney. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6797099/ · DOI 10.1620/tjem.134.55

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 54–60

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nine men in oral lysine tests; three men in intravenous amino-acid loading tests. · source_derived_draft · unverified_draft

## arg-renal-competition Related amino acids interacted at a kidney transport step. Amino-acid loading experiments indicated inhibition of renal citrulline transport by arginine, lysine and ornithine. Model: Nine men in oral lysine tests; three men in intravenous amino-acid loading tests. Limitations: Small historical experiment; no molecular transporter identified and no ordinary-meal effect size established. Evidence access: Primary abstract A new transport interaction of dibasic amino acids and citrulline in human kidney. · 1981 · https://pubmed.ncbi.nlm.nih.gov/6797099/ · DOI 10.1620/tjem.134.55