L-Ornithine

evidence_span

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experimental_model

Human AGAT crystal structures and inactive-mutant substrate complex

exposure

Native, ornithine-bound and inactive mutant structures

limitations

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

nutrient_topic

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

organism

Recombinant human enzyme

plain_language

A product of the first step can bind back to the enzyme and change its working shape.

primary_references

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

tissue_or_cell_type

Purified protein

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 190–201

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

### creatine-ornithine-agat Ornithine binding to human AGAT induced movement of a flexible loop and neighboring helix at the active-site region. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A product of the first step can bind back to the enzyme and change its working shape. organism: Recombinant human enzyme tissue_or_cell_type: Purified protein experimental_model: Human AGAT crystal structures and inactive-mutant substrate complex limitations: Structures support an amidino-transfer mechanism; substrate availability in a person and effects of amino-acid supplementation were not measured. exposure: Native, ornithine-bound and inactive mutant structures evidence_span: {"source_cache": "artifacts/creatine-research/9218780.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b", "start_char": 0, "end_char": 1112, "text_sha256": "407baedc2f982a5abb9d14a01e8ac9dc331d60115acc716604c1e6003aa12c1b"} [creatine-p9218780] Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. (1997). https://pubmed.ncbi.nlm.nih.gov/9218780/ DOI: 10.1093/emboj/16.12.3373

evidence_access

Primary full text

experimental_model

Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline.

limitations

The ornithine experiment used conditions the authors regarded as likely nonphysiological; no universal exclusive routing rule is inferred.

nutrient_topic

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

plain_language

Two precursor routes can feed the same product through differently placed enzymes.

primary_references

Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 38–44

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline. · source_derived_draft · unverified_draft

## l-proline-precursor-routing Two precursor routes can feed the same product through differently placed enzymes. Isotope tracing with gene silencing linked glutamine/glutamate-derived proline mainly to PYCR1/PYCR2 and ornithine-derived proline mainly to PYCRL in human melanoma cells. Model: Lu1205 cells; 1 mM labeled precursors for eight hours; ornithine labeling required omission of extracellular proline. Limitations: The ornithine experiment used conditions the authors regarded as likely nonphysiological; no universal exclusive routing rule is inferred. Evidence access: Primary full text Functional specialization in proline biosynthesis of melanoma. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23024808/ · DOI 10.1371/journal.pone.0045190

evidence_access

Primary abstract

experimental_model

Recombinant human OAT structure and described catalytic reaction.

limitations

Reversible pathway; net flux depends on tissue and substrate conditions.

nutrient_topic

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

plain_language

Ornithine also feeds a pathway connected to proline metabolism.

primary_references

Crystal structure of human recombinant ornithine aminotransferase. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9514741/ · DOI 10.1006/jmbi.1997.1583

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 118–124

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

## arg-oat-reaction Ornithine also feeds a pathway connected to proline metabolism. OAT transfers the ornithine delta-amino group to 2-oxoglutarate, producing glutamate-5-semialdehyde and glutamate. Model: Recombinant human OAT structure and described catalytic reaction. Limitations: Reversible pathway; net flux depends on tissue and substrate conditions. Evidence access: Primary abstract Crystal structure of human recombinant ornithine aminotransferase. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9514741/ · DOI 10.1006/jmbi.1997.1583

evidence_access

Primary abstract and indexed primary full-text introduction, PMC1904517

experimental_model

Human ODC study; reaction identified in the primary paper introduction.

limitations

Reaction identity does not establish net pathway flux after supplementation.

nutrient_topic

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

plain_language

This reaction opens the polyamine branch.

primary_references

A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 110–116

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human ODC study; reaction identified in the primary paper introduction. · source_derived_draft · unverified_draft

## arg-odc-reaction This reaction opens the polyamine branch. ODC catalyzes conversion of ornithine into putrescine. Model: Human ODC study; reaction identified in the primary paper introduction. Limitations: Reaction identity does not establish net pathway flux after supplementation. Evidence access: Primary abstract and indexed primary full-text introduction, PMC1904517 A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

evidence_access

Primary full text; Figure 4B

experimental_model

Recombinant human GATM substrate comparison.

limitations

Taurine is a secondary substrate in this assay; tissue flux and clinically important depletion were not established.

nutrient_topic

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

plain_language

Creatine-synthesis machinery also accepts a taurine-related side reaction.

primary_references

Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 188–194

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human GATM substrate comparison. · source_derived_draft · unverified_draft

## agmatine-sulfate-gatm-taurine Creatine-synthesis machinery also accepts a taurine-related side reaction. Purified human GATM transferred an amidino group from arginine to taurine, producing taurocyamine in vitro. Model: Recombinant human GATM substrate comparison. Limitations: Taurine is a secondary substrate in this assay; tissue flux and clinically important depletion were not established. Evidence access: Primary full text; Figure 4B Guanidino acid hydrolysis by the human enzyme annotated as agmatinase. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36543883/ · DOI 10.1038/s41598-022-26655-4

evidence_span

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experimental_model

Human AGAT crystal structures and inactive-mutant substrate complex

exposure

Native, ornithine-bound and inactive mutant structures

limitations

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

nutrient_topic

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

organism

Recombinant human enzyme

plain_language

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

primary_references

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

tissue_or_cell_type

Purified protein

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/creatine-research/29506905.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66", "start_char": 0, "end_char": 1609, "text_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66"}

experimental_model

International retrospective registry

exposure

All received creatine; 18 ornithine and 15 arginine/protein restriction

limitations

Nonrandomized combination treatment and variable diagnosis timing prevent attribution of improvements to a single component.

nutrient_topic

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

organism

22 people with GAMT deficiency

plain_language

The registry supports the importance of treating this disorder, but cannot tell us which component caused each improvement.

primary_references

[creatine-p29506905] Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. (2018). https://pubmed.ncbi.nlm.nih.gov/29506905/ DOI: 10.1016/j.ejpn.2018.02.007

tissue_or_cell_type

Clinical outcomes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 893–904

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

### creatine-gamt-combination-outcomes In the GAMT registry, clinical severity improved in 13 patients, 11 became seizure-free and movement disorder resolved in four during treatment combinations. Condition category: machinery_impairment nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The registry supports the importance of treating this disorder, but cannot tell us which component caused each improvement. organism: 22 people with GAMT deficiency tissue_or_cell_type: Clinical outcomes experimental_model: International retrospective registry limitations: Nonrandomized combination treatment and variable diagnosis timing prevent attribution of improvements to a single component. exposure: All received creatine; 18 ornithine and 15 arginine/protein restriction evidence_span: {"source_cache": "artifacts/creatine-research/29506905.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66", "start_char": 0, "end_char": 1609, "text_sha256": "e443eeda80f65e6e7cd3b0b07a4a86b5f11b6b4feef6201ce97a99bc27af0b66"} [creatine-p29506905] Treatment outcome of twenty-two patients with guanidinoacetate methyltransferase deficiency: An international retrospective cohort study. (2018). https://pubmed.ncbi.nlm.nih.gov/29506905/ DOI: 10.1016/j.ejpn.2018.02.007

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_span

{"source_cache": "artifacts/citrulline-research/6401349.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545", "start_char": 0, "end_char": 349, "text_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545"}

experimental_model

Clinical oral-intermediate comparison

exposure

Oral citrulline, arginine or ornithine

limitations

Brief indexed abstract; no trial size or dosing is inferred; not evidence that citrulline replaces lysine.

nutrient_topic

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

organism

Human lysinuric protein intolerance

plain_language

The alternative precursor improved downstream amino-acid availability in this disorder.

primary_references

[citrulline-p6401349] Oral administration of urea cycle intermediates in lysinuric protein intolerance: effect on plasma and urinary arginine and ornithine. (1983). https://pubmed.ncbi.nlm.nih.gov/6401349/ DOI: 10.1016/0026-0495(83)90154-3

tissue_or_cell_type

Plasma urea-cycle intermediates

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 853–864

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

### citrulline-lpi-precursor-response Oral citrulline raised plasma urea-cycle intermediates more than oral arginine or ornithine in the LPI report. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The alternative precursor improved downstream amino-acid availability in this disorder. organism: Human lysinuric protein intolerance tissue_or_cell_type: Plasma urea-cycle intermediates experimental_model: Clinical oral-intermediate comparison limitations: Brief indexed abstract; no trial size or dosing is inferred; not evidence that citrulline replaces lysine. exposure: Oral citrulline, arginine or ornithine evidence_span: {"source_cache": "artifacts/citrulline-research/6401349.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545", "start_char": 0, "end_char": 349, "text_sha256": "e98ad3132221fd0deae9dd89d6c14a4f6b010655656a6e0ea44a7c47f2ca1545"} [citrulline-p6401349] Oral administration of urea cycle intermediates in lysinuric protein intolerance: effect on plasma and urinary arginine and ornithine. (1983). https://pubmed.ncbi.nlm.nih.gov/6401349/ DOI: 10.1016/0026-0495(83)90154-3

evidence_span

{"source_cache": "artifacts/citrulline-research/9514741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0", "start_char": 0, "end_char": 2979, "text_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0"}

experimental_model

Recombinant enzyme crystal structure

exposure

PLP-bound enzyme structure

limitations

The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine.

nutrient_topic

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

organism

Human OAT

plain_language

Vitamin B6 has a defined role in the machinery handling ornithine.

primary_references

[citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

tissue_or_cell_type

Mitochondrial ornithine transamination

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 333–344

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

### citrulline-oat-plp Human OAT bound pyridoxal phosphate through a Schiff base to Lys292. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B6 has a defined role in the machinery handling ornithine. organism: Human OAT tissue_or_cell_type: Mitochondrial ornithine transamination experimental_model: Recombinant enzyme crystal structure limitations: The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine. exposure: PLP-bound enzyme structure evidence_span: {"source_cache": "artifacts/citrulline-research/9514741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0", "start_char": 0, "end_char": 2979, "text_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0"} [citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

evidence_span

{"source_cache": "artifacts/citrulline-research/9514741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0", "start_char": 0, "end_char": 2979, "text_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0"}

experimental_model

Recombinant enzyme crystal structure

exposure

PLP-bound enzyme structure

limitations

The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine.

nutrient_topic

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

organism

Human OAT

plain_language

This is an ornithine-processing reaction; its direction depends on the biological setting.

primary_references

[citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

tissue_or_cell_type

Mitochondrial ornithine transamination

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 346–357

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

### citrulline-oat-reaction OAT transfers the ornithine delta-amino group to 2-oxoglutarate, yielding glutamate and glutamate semialdehyde, which cyclizes to P5C. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This is an ornithine-processing reaction; its direction depends on the biological setting. organism: Human OAT tissue_or_cell_type: Mitochondrial ornithine transamination experimental_model: Recombinant enzyme crystal structure limitations: The described reaction direction is ornithine transamination; this structure alone does not quantify reverse flux in human intestine. exposure: PLP-bound enzyme structure evidence_span: {"source_cache": "artifacts/citrulline-research/9514741.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0", "start_char": 0, "end_char": 2979, "text_sha256": "cca17abd35f0211a043dd3cc8883369e230209206ff62b62242197f90201cea0"} [citrulline-p9514741] Crystal structure of human recombinant ornithine aminotransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9514741/ DOI: 10.1006/jmbi.1997.1583

evidence_span

{"source_cache": "artifacts/citrulline-research/38940639.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eca9d57812cf3d8efe7c0beb62b9b364cc25e1aeca647c95e4abf0fd9eb8365", "start_char": 194, "end_char": 364, "text_sha256": "c5ddbcd5c91cfcdc72d6e556c77228f8ecd6c25ebaa3c25fd9617f6baa145692"}

experimental_model

Recombinant enzyme site-directed mutagenesis and kinetic assays

exposure

Ornithine and carbamoyl phosphate; active-site and remote variants

limitations

Recombinant mutation experiments; do not equate altered enzyme function with a dietary shortage.

nutrient_topic

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

organism

Human OTC

plain_language

Citrulline is built from ornithine and a nitrogen-containing carbamoyl group.

primary_references

[citrulline-p38940639] Revisiting the Roles of Catalytic Residues in Human Ornithine Transcarbamylase. (2024). https://pubmed.ncbi.nlm.nih.gov/38940639/ DOI: 10.1021/acs.biochem.4c00206

tissue_or_cell_type

Mitochondrial urea-cycle enzyme

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 203–214

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme site-directed mutagenesis and kinetic assays · source_derived_draft · unverified_draft

### citrulline-otc-citrulline Human OTC converts ornithine and carbamoyl phosphate into citrulline, releasing inorganic phosphate. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrulline is built from ornithine and a nitrogen-containing carbamoyl group. organism: Human OTC tissue_or_cell_type: Mitochondrial urea-cycle enzyme experimental_model: Recombinant enzyme site-directed mutagenesis and kinetic assays limitations: Recombinant mutation experiments; do not equate altered enzyme function with a dietary shortage. exposure: Ornithine and carbamoyl phosphate; active-site and remote variants evidence_span: {"source_cache": "artifacts/citrulline-research/38940639.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eca9d57812cf3d8efe7c0beb62b9b364cc25e1aeca647c95e4abf0fd9eb8365", "start_char": 194, "end_char": 364, "text_sha256": "c5ddbcd5c91cfcdc72d6e556c77228f8ecd6c25ebaa3c25fd9617f6baa145692"} [citrulline-p38940639] Revisiting the Roles of Catalytic Residues in Human Ornithine Transcarbamylase. (2024). https://pubmed.ncbi.nlm.nih.gov/38940639/ DOI: 10.1021/acs.biochem.4c00206

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"}

experimental_model

Patient genetics and recombinant variant expression

exposure

ALDH18A1 R84Q compared with wild-type isoforms

limitations

Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.

nutrient_topic

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

organism

Human, two siblings and mammalian expression systems

plain_language

Low citrulline can arise from a defective upstream enzyme.

primary_references

[citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853

tissue_or_cell_type

Mitochondrial P5CS and circulating amino acids

trigger_kind

machinery_impairment Imported condition classification; unverified.

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 320–331

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient genetics and recombinant variant expression · source_derived_draft · unverified_draft

### citrulline-p5cs-low-citrulline The two R84Q siblings had hypocitrullinemia with low ornithine, arginine and proline; the variant strongly reduced expressed P5CS activity. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low citrulline can arise from a defective upstream enzyme. organism: Human, two siblings and mammalian expression systems tissue_or_cell_type: Mitochondrial P5CS and circulating amino acids experimental_model: Patient genetics and recombinant variant expression limitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype. exposure: ALDH18A1 R84Q compared with wild-type isoforms evidence_span: {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"} [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853

experimental_model

X-ray structures of human ARG1 with boronic-acid transition-state analogues

exposure

ABH and BEC inhibitor complexes

limitations

Transition-state analogue crystallography and author mechanistic inference; not direct nutritional manganese restriction.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

ARG1 holds two manganese ions at the site where arginine is hydrolyzed.

primary_references

[mn-enz-16141327] Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. (2005). https://pubmed.ncbi.nlm.nih.gov/16141327/ DOI: 10.1073/pnas.0504027102

tissue_or_cell_type

Purified ARG1

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 534–544

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of human ARG1 with boronic-acid transition-state analogues · source_derived_draft · unverified_draft

### mn-enz-arg1-binuclear-transition-state Human ARG1 structures show a binuclear manganese site binding a boronate transition-state analogue, supporting metal stabilization of the arginine-hydrolysis transition state. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: ARG1 holds two manganese ions at the site where arginine is hydrolyzed. organism: Homo sapiens protein tissue_or_cell_type: Purified ARG1 experimental_model: X-ray structures of human ARG1 with boronic-acid transition-state analogues limitations: Transition-state analogue crystallography and author mechanistic inference; not direct nutritional manganese restriction. exposure: ABH and BEC inhibitor complexes [mn-enz-16141327] Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. (2005). https://pubmed.ncbi.nlm.nih.gov/16141327/ DOI: 10.1073/pnas.0504027102

experimental_model

Recombinant human ARG2 expressed in E. coli and purified

exposure

Substrate/product kinetics

limitations

Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

ARG2 breaks arginine into ornithine and urea.

primary_references

[mn-enz-11370664] Expression, purification, and characterization of human type II arginase. (2001). https://pubmed.ncbi.nlm.nih.gov/11370664/ DOI: 10.1006/abbi.2001.2324

tissue_or_cell_type

Purified ARG2

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 572–582

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human ARG2 expressed in E. coli and purified · source_derived_draft · unverified_draft

### mn-enz-arg2-hydrolysis Purified recombinant human ARG2 catalyzes arginine hydrolysis to ornithine and urea. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: ARG2 breaks arginine into ornithine and urea. organism: Homo sapiens protein tissue_or_cell_type: Purified ARG2 experimental_model: Recombinant human ARG2 expressed in E. coli and purified limitations: Primary experimental scope only; no human dietary threshold, clinical treatment rule, or universal metal substitution is established. exposure: Substrate/product kinetics [mn-enz-11370664] Expression, purification, and characterization of human type II arginase. (2001). https://pubmed.ncbi.nlm.nih.gov/11370664/ DOI: 10.1006/abbi.2001.2324

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

Human and Leishmania ODC comparison; human inhibitor-bound structure.

limitations

Cofactor dependence does not establish that extra B6 raises polyamines in a replete person.

nutrient_topic

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

plain_language

The polyamine branch connects to vitamin B6.

primary_references

A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 102–108

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human and Leishmania ODC comparison; human inhibitor-bound structure. · source_derived_draft · unverified_draft

## arg-odc-cofactor The polyamine branch connects to vitamin B6. Biochemical binding and structural experiments identify PLP as the human ODC coenzyme. Model: Human and Leishmania ODC comparison; human inhibitor-bound structure. Limitations: Cofactor dependence does not establish that extra B6 raises polyamines in a replete person. Evidence access: Primary abstract A structural insight into the inhibition of human and Leishmania donovani ornithine decarboxylases by 1-amino-oxy-3-aminopropane. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17407445/ · DOI 10.1042/bj20070188

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

evidence_access

Full-text results, Figures 2 and 6, Europe PMC PMC5075284; primary abstract.

experimental_model

Primary human activated T cells; isotope tracing and functional assays.

limitations

Flux is model-specific; not evidence of clinical wound healing.

nutrient_topic

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

plain_language

Arginine fed more than the NO pathway.

primary_references

L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27745970/ · DOI 10.1016/j.cell.2016.09.031

L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 222–228

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human activated T cells; isotope tracing and functional assays. · source_derived_draft · unverified_draft

## arg-tcell-carbon Arginine fed more than the NO pathway. Tracer carbon appeared in putrescine and proline; arginase inhibition reduced these labeled products. Model: Primary human activated T cells; isotope tracing and functional assays. Limitations: Flux is model-specific; not evidence of clinical wound healing. Evidence access: Full-text results, Figures 2 and 6, Europe PMC PMC5075284; primary abstract. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27745970/ · DOI 10.1016/j.cell.2016.09.031