Formate: A New Frontier in Fetal One‐Carbon Metabolism
Bibliographic record
Abstract
For years the significance of formate in one‐carbon metabolism has been underappreciated. It is known that formate can be produced by the mitochondria and incorporated into the cytosolic tetrahydrofolate pool where its carbon is used for three canonical processes i) purine synthesis ii) thymidylate synthesis and iii) transmethylation reactions. Our lab has recently reported on elevated levels of formate in the plasma of fetal and neonatal sheep which decline after birth (Washburn et al. 2015, AJP). We now report a similar phenomenon in rats where fetal rat pups at 19 ± 1 days gestational age have high levels of plasma formate (225 ± 42.1 μM) which decline after birth to normal adult levels by 4–5 weeks of age (60.8 ± 19.8 μM). In parallel with our sheep data, we find elevated formate concentration in the amniotic fluid taken from the fetal pups at day 19 of gestation. Infusion of 13 C‐formate into pregnant rats showed that very little formate crosses the placenta suggesting that fetal formate is either produced by the placenta or synthesized in the fetus. We isolated placental mitochondria to determine their capacity for producing formate. Our results show that placental mitochondria are just as effective as liver mitochondria from both pregnant and non‐pregnant rats at producing formate from serine (). These data suggest a critical role for formate in fetal one‐carbon metabolism. Support or Funding Information Funded by the Research and Development Corporation of Newfoundland and Labrador (RDC) and the Canadian Institutes of Health Research (CIHR). Source of Mitochondria Formate production (nmol formate/mg protein/10 mins) Placenta 3.13 ± 2.11 Liver (Pregnant rat) 3.02 ± 3.77 Liver (Non‐Pregnant rat) 3.18 ± 0.84 Formate production from isolated mitochondria using serine as one‐carbon donor.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.002 | 0.004 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".