Guanosine triphosphate

evidence_access

Primary abstract

experimental_model

Human lymphoblast enzyme assays from eight unrelated affected children and controls.

limitations

GTP regulation is not evidence that dietary purines or glutamate normalize the disease.

nutrient_topic

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

plain_language

An energy-related nucleotide restrains glutamate oxidation.

primary_references

Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 170–176

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lymphoblast enzyme assays from eight unrelated affected children and controls. · source_derived_draft · unverified_draft

## glutamate-gdh-gtp-control An energy-related nucleotide restrains glutamate oxidation. Human GLUD1 activity was inhibited by GTP; patient-derived regulatory variants showed reduced sensitivity to that inhibition. Model: Human lymphoblast enzyme assays from eight unrelated affected children and controls. Limitations: GTP regulation is not evidence that dietary purines or glutamate normalize the disease. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904

evidence_access

Primary abstract

experimental_model

Human enzyme kinetics and cellular/yeast functional studies.

limitations

Results depend on the mature protein construct; do not infer benefit from dietary nucleotide supplements.

nutrient_topic

Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine

plain_language

The modifying complex includes a GTP-powered component.

primary_references

The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33619562/ · DOI 10.1093/nar/gkab104

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 265–271

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme kinetics and cellular/yeast functional studies. · source_derived_draft · unverified_draft

## taurine-gtpbp3-gtpase The modifying complex includes a GTP-powered component. Purified mature human GTPBP3 exhibited GTPase activity, and functional experiments linked that activity to tRNA modification. Model: Human enzyme kinetics and cellular/yeast functional studies. Limitations: Results depend on the mature protein construct; do not infer benefit from dietary nucleotide supplements. Evidence access: Primary abstract The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33619562/ · DOI 10.1093/nar/gkab104

cross_nutrient

false

evidence_location

Indexed primary abstract; indexed Results

experimental_model

Purified human proteins

exposure

GTP hydrolysis assay

limitations

Biochemical reconstitution; does not determine cellular rate or dietary requirement.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Human MMAA consumed GTP in the protein assay, linking energy use to B12 handling.

primary_references

[froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717

tissue_or_cell_type

Purified protein assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1033–1045

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

### mmaa-hydrolyzes-gtp Purified human MMAA displayed intrinsic GTPase activity modulated by human MMUT. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human MMAA consumed GTP in the protein assay, linking energy use to B12 handling. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Biochemical reconstitution; does not determine cellular rate or dietary requirement. exposure: GTP hydrolysis assay cross_nutrient: false evidence_location: Indexed primary abstract; indexed Results [froese-2010-human-mmaa] Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. (2010). https://pubmed.ncbi.nlm.nih.gov/20876572/ DOI: 10.1074/jbc.m110.177717

evidence_access

Primary full text, in-vitro reconstitution methods and results

experimental_model

Human enzyme-complex reconstitution and mass spectrometry.

limitations

The reaction mixture also contained GTP, ATP, FAD, NADH, NADPH and magnesium; their presence alone does not demonstrate each is individually limiting.

nutrient_topic

Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine

plain_language

Two proteins join taurine and a folate-derived carbon unit onto mitochondrial tRNA.

primary_references

Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29390138/ · DOI 10.1093/nar/gky068

Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 201–207

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme-complex reconstitution and mass spectrometry. · source_derived_draft · unverified_draft

## taurine-mto1-gtpbp3 Two proteins join taurine and a folate-derived carbon unit onto mitochondrial tRNA. Reconstituting the human MTO1-GTPBP3 complex with hypomodified mitochondrial tRNA, taurine and 5,10-methylene-THF produced the taurine-containing U34 modification. Model: Human enzyme-complex reconstitution and mass spectrometry. Limitations: The reaction mixture also contained GTP, ATP, FAD, NADH, NADPH and magnesium; their presence alone does not demonstrate each is individually limiting. Evidence access: Primary full text, in-vitro reconstitution methods and results Metabolic and chemical regulation of tRNA modification associated with taurine deficiency and human disease. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29390138/ · DOI 10.1093/nar/gky068

cross_nutrient

false

evidence_location

Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods

experimental_model

Purified human proteins

exposure

Anaerobic assay; MMAB, MMAA, GTP and ATP

limitations

Reconstituted transfer; spectroscopy reports cofactor environment, not cellular turnover.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

In the purified repair assay, inactive B12 moved from MMUT back to MMAB.

primary_references

[mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4

tissue_or_cell_type

Purified protein assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1131–1143

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

### mmaa-mmab-offload-cob-ii A human MMAA/MMAB repair mixture with GTP and ATP transferred cob(II)alamin from MMUT to MMAB in anaerobic spectroscopy. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In the purified repair assay, inactive B12 moved from MMUT back to MMAB. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Reconstituted transfer; spectroscopy reports cofactor environment, not cellular turnover. exposure: Anaerobic assay; MMAB, MMAA, GTP and ATP cross_nutrient: false evidence_location: Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4

cross_nutrient

false

evidence_location

Indexed primary abstract

experimental_model

Purified human proteins

exposure

MMAA added after 60-minute catalytic inactivation

limitations

In-vitro reactivation; abstract interprets damaged-cofactor exchange rather than measuring every intermediate.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

MMAA restarted an inactive purified human MMUT reaction in a GTP-dependent assay.

primary_references

[takahashi-2010-mmaa-repair] Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein. (2011). https://pubmed.ncbi.nlm.nih.gov/21138732/ DOI: 10.1016/j.bbrc.2010.11.141

tissue_or_cell_type

Purified protein assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1089–1101

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

### mmaa-reactivates-mmut Adding MMAA after 60 minutes restored activity in an inactivated human MMUT reaction through GTP hydrolysis. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: MMAA restarted an inactive purified human MMUT reaction in a GTP-dependent assay. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: In-vitro reactivation; abstract interprets damaged-cofactor exchange rather than measuring every intermediate. exposure: MMAA added after 60-minute catalytic inactivation cross_nutrient: false evidence_location: Indexed primary abstract [takahashi-2010-mmaa-repair] Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein. (2011). https://pubmed.ncbi.nlm.nih.gov/21138732/ DOI: 10.1016/j.bbrc.2010.11.141

evidence_access

Primary abstract

experimental_model

Mouse-cell isolated mitochondrial experiments.

limitations

The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep.

nutrient_topic

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

plain_language

The pathway has several gates, with different requirements at different steps.

primary_references

Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 276–282

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

## l-cysteine-nfs1-persulfide-gate The pathway has several gates, with different requirements at different steps. Labeled NFS1-bound persulfide was an intermediate; its sulfur release required iron, GTP and NADH, whereas ATP was required for the overall assembly pathway but not this release step. Model: Mouse-cell isolated mitochondrial experiments. Limitations: The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402

evidence_span

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experimental_model

Recombinant heterodimer purification and enzyme kinetics

exposure

NO donor and YC-1 activation; GTP, cGMP and pyrophosphate kinetics

limitations

Purified-enzyme study; not a citrulline supplementation trial.

nutrient_topic

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

organism

Human alpha1-beta1 sGC expressed in insect cells

plain_language

The NO receptor makes a second messenger, cGMP, linking the initial signal to downstream responses.

primary_references

[citrulline-p10995472] Human recombinant soluble guanylyl cyclase: expression, purification, and regulation. (2000). https://pubmed.ncbi.nlm.nih.gov/10995472/ DOI: 10.1073/pnas.190333697

tissue_or_cell_type

GTP conversion, heme and product inhibition

Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 489–500

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

### citrulline-sgc-cgmp Recombinant human soluble guanylate cyclase converted GTP to cGMP and pyrophosphate; both products inhibited enzyme activity in the kinetic assays. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The NO receptor makes a second messenger, cGMP, linking the initial signal to downstream responses. organism: Human alpha1-beta1 sGC expressed in insect cells tissue_or_cell_type: GTP conversion, heme and product inhibition experimental_model: Recombinant heterodimer purification and enzyme kinetics limitations: Purified-enzyme study; not a citrulline supplementation trial. exposure: NO donor and YC-1 activation; GTP, cGMP and pyrophosphate kinetics evidence_span: {"source_cache": "artifacts/citrulline-research/10995472.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c117699ec7c07cc54d779cc0e8274c07555b0ec93498daa8a484652edc219244", "start_char": 0, "end_char": 1300, "text_sha256": "c117699ec7c07cc54d779cc0e8274c07555b0ec93498daa8a484652edc219244"} [citrulline-p10995472] Human recombinant soluble guanylyl cyclase: expression, purification, and regulation. (2000). https://pubmed.ncbi.nlm.nih.gov/10995472/ DOI: 10.1073/pnas.190333697

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation.

limitations

Host cell species and human protein identity are distinct; no intake intervention was tested.

nutrient_topic

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

plain_language

Changing the enzyme altered its response to a brake.

primary_references

Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Glutamate / L-glutamic acid: carbon and nitrogen allocation, signaling and cross-nutrient mechanisms (2026-09-19) · lines 178–184

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation. · source_derived_draft · unverified_draft

## glutamate-gdh-regulatory-variants Changing the enzyme altered its response to a brake. Expressing a patient GLUD1 mutant in COS7 cells reproduced reduced GTP inhibition observed in the patient lymphoblasts. Model: Human disease variant expressed in nonhuman COS7 host cells; biochemical confirmation. Limitations: Host cell species and human protein identity are distinct; no intake intervention was tested. Evidence access: Primary abstract Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9571255/ · DOI 10.1056/NEJM199805073381904

evidence_span

{"source_cache": "artifacts/molybdenum-research/31996372.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a88a2e2c4aae83293fa6f1860d10bb41b41c32d1ad79b0b04cd5dd3eb02865c7", "start_char": 0, "end_char": 1846, "text_sha256": "a88a2e2c4aae83293fa6f1860d10bb41b41c32d1ad79b0b04cd5dd3eb02865c7"}

experimental_model

Alternative splicing, fluorescence microscopy, fractionation and mitochondrial targeting of human MOCS1 proteins

exposure

Type I-III MOCS1 splice constructs

limitations

Localization and processing experiments; no dietary iron, SAM or molybdenum intervention.

nutrient_topic

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

organism

Homo sapiens

plain_language

The cofactor scaffold is built from GTP before molybdenum is inserted.

primary_references

[mo-p31996372] Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism. (2020). https://pubmed.ncbi.nlm.nih.gov/31996372/ DOI: 10.1074/jbc.ra119.010720

tissue_or_cell_type

Transfected human-cell localization and mitochondrial matrix

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 274–285

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Alternative splicing, fluorescence microscopy, fractionation and mitochondrial targeting of human MOCS1 proteins · source_derived_draft · unverified_draft

### mo-mocs1-cpmp MOCS1A and MOCS1B jointly support conversion of GTP to cPMP, the first intermediate of human Moco synthesis. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor scaffold is built from GTP before molybdenum is inserted. organism: Homo sapiens tissue_or_cell_type: Transfected human-cell localization and mitochondrial matrix experimental_model: Alternative splicing, fluorescence microscopy, fractionation and mitochondrial targeting of human MOCS1 proteins limitations: Localization and processing experiments; no dietary iron, SAM or molybdenum intervention. exposure: Type I-III MOCS1 splice constructs evidence_span: {"source_cache": "artifacts/molybdenum-research/31996372.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a88a2e2c4aae83293fa6f1860d10bb41b41c32d1ad79b0b04cd5dd3eb02865c7", "start_char": 0, "end_char": 1846, "text_sha256": "a88a2e2c4aae83293fa6f1860d10bb41b41c32d1ad79b0b04cd5dd3eb02865c7"} [mo-p31996372] Alternative splicing of the bicistronic gene molybdenum cofactor synthesis 1 (MOCS1) uncovers a novel mitochondrial protein maturation mechanism. (2020). https://pubmed.ncbi.nlm.nih.gov/31996372/ DOI: 10.1074/jbc.ra119.010720

experimental_model

Purified protein reconstitution

limitations

Biochemical amplification is not a nutritional dose response.

nutrient_topic

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

organism

Bos taurus

plain_language

Activated pigment switches transducin into its signaling state.

primary_references

[fung-1981] Flow of information in the light-triggered cyclic nucleotide cascade of vision (1981). https://pubmed.ncbi.nlm.nih.gov/6264430/ DOI: 10.1073/pnas.78.1.152

tissue_or_cell_type

Rod outer-segment protein system

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 905–914

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

### a-vision-transducin-exchange Photoactivated rhodopsin catalyzed GDP-to-GTP nucleotide exchange on transducin in reconstituted bovine rod preparations. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated pigment switches transducin into its signaling state. organism: Bos taurus tissue_or_cell_type: Rod outer-segment protein system experimental_model: Purified protein reconstitution limitations: Biochemical amplification is not a nutritional dose response. [fung-1981] Flow of information in the light-triggered cyclic nucleotide cascade of vision (1981). https://pubmed.ncbi.nlm.nih.gov/6264430/ DOI: 10.1073/pnas.78.1.152