Formate: A New Frontier in Fetal One‐Carbon Metabolism

• Published in: The FASEB Journal
• Main Authors: MacMillan, Luke, Harnett, Brian J, Quilty, Rebecca, Tingley, Garrett, Brosnan, Margaret E., Brosnan, John T.
• Other Authors: Research and Development Corporation of Newfoundland and Labrador, Canadian Institutes of Health Research
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2016
• Subjects: Newfoundland; Washburn
• Online Access: http://dx.doi.org/10.1096/fasebj.30.1_supplement.1171.3

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 ( Table 1 ). 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.