Component
Nuclear de novo thymidylate synthesis
Defined biochemical process or measured endpoint; not a unique causal entity for an entire sentence.
3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What acts on it
Patient fibroblasts showed roughly half the formate-derived contribution to dTMP measured in control cells.
Experimental context and source evidence
- availability_state
- machinery_impairment Imported condition classification; unverified.
- experimental_model
- Stable-isotope tracing
- exposure
- Assay conditions described in the linked primary study.
- limitations
- One genotype; isotope ratio is not a whole-body folate measurement.
- nutrient_topic
- Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
- organism
- Homo sapiens
- plain_language
- This inherited enzyme defect reduced one carbon supply for a DNA base.
- primary_references
- [field-2015] Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis (2015). https://pubmed.ncbi.nlm.nih.gov/25548164/ DOI: 10.1073/pnas.1414555112
- tissue_or_cell_type
- WG3607 fibroblasts
- trigger_kind
- machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1170–1180
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracing · source_derived_draft · unverified_draft
### mthfd1-patient-dtmp Patient fibroblasts showed roughly half the formate-derived contribution to dTMP measured in control cells. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inherited enzyme defect reduced one carbon supply for a DNA base. organism: Homo sapiens tissue_or_cell_type: WG3607 fibroblasts experimental_model: Stable-isotope tracing limitations: One genotype; isotope ratio is not a whole-body folate measurement. exposure: Assay conditions described in the linked primary study. [field-2015] Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis (2015). https://pubmed.ncbi.nlm.nih.gov/25548164/ DOI: 10.1073/pnas.1414555112
Complete structured claim and evidenceShmt1-transgenic mouse liver had lower nuclear SHMT1/TYMS and lower nuclear de novo dTMP synthesis despite higher total enzyme abundance.
Experimental context and source evidence
- availability_state
- machinery_impairment Imported condition classification; unverified.
- experimental_model
- Transgene and isolated-nuclei assays
- exposure
- Assay conditions described in the linked primary study.
- limitations
- Overexpression phenotype must not be generalized to supplementation.
- nutrient_topic
- Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
- organism
- Mus musculus
- plain_language
- More enzyme in the whole cell did not mean more at DNA-replication sites.
- primary_references
- [macfarlane-2011] Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA (2011). https://pubmed.ncbi.nlm.nih.gov/22057276/ DOI: 10.1074/jbc.m111.307629
- tissue_or_cell_type
- Liver nuclei
- trigger_kind
- machinery_impairment Imported condition classification; unverified.
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1145–1155
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transgene and isolated-nuclei assays · source_derived_draft · unverified_draft
### shmt1-transgene-nuclear-mislocalization Shmt1-transgenic mouse liver had lower nuclear SHMT1/TYMS and lower nuclear de novo dTMP synthesis despite higher total enzyme abundance. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: More enzyme in the whole cell did not mean more at DNA-replication sites. organism: Mus musculus tissue_or_cell_type: Liver nuclei experimental_model: Transgene and isolated-nuclei assays limitations: Overexpression phenotype must not be generalized to supplementation. exposure: Assay conditions described in the linked primary study. [macfarlane-2011] Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA (2011). https://pubmed.ncbi.nlm.nih.gov/22057276/ DOI: 10.1074/jbc.m111.307629
Complete structured claim and evidence
Where it participates (unsigned role)
Nuclear MTHFD1 supplies formate-derived one-carbon units for thymidylate synthesis through its folate-interconversion activities.
Experimental context and source evidence
- cross_nutrient
- ATP and NADPH support folate-mediated carbon use.
- experimental_model
- Localization and folate-pathway experiments
- exposure
- Assay conditions described in the linked primary study.
- limitations
- Compartmental flux varies with cell cycle.
- nutrient_topic
- Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
- organism
- Homo sapiens
- plain_language
- Formate can feed DNA-base production inside the nucleus.
- primary_references
- [field-2014] Nuclear enrichment of folate cofactors and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) protect de novo thymidylate biosynthesis during folate deficiency (2014). https://pubmed.ncbi.nlm.nih.gov/25213861/ DOI: 10.1074/jbc.m114.599589
- tissue_or_cell_type
- HeLa and MCF7 cells
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 936–947
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Localization and folate-pathway experiments · source_derived_draft · unverified_draft
### mthfd1-formate-nuclear-carbon Nuclear MTHFD1 supplies formate-derived one-carbon units for thymidylate synthesis through its folate-interconversion activities. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Formate can feed DNA-base production inside the nucleus. organism: Homo sapiens tissue_or_cell_type: HeLa and MCF7 cells experimental_model: Localization and folate-pathway experiments limitations: Compartmental flux varies with cell cycle. exposure: Assay conditions described in the linked primary study. cross_nutrient: ATP and NADPH support folate-mediated carbon use. [field-2014] Nuclear enrichment of folate cofactors and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) protect de novo thymidylate biosynthesis during folate deficiency (2014). https://pubmed.ncbi.nlm.nih.gov/25213861/ DOI: 10.1074/jbc.m114.599589
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.