Formate metabolism in vivo: the effect of vitamin deficiencies and changes due to pregnancy

Formate is the simplest of the carboxylic acids and is used in vivo as a source of one-carbon units for DNA synthesis and methylation reactions. It has also been found to play a critical role in neural tube closure during fetal development.

One-carbon metabolism relies heavily on the involvement of B-vitamins, notably folate, vitamin B6 , vitamin B12, and riboflavin. Previous studies from our lab have determined that plasma formate levels are sensitive to folate and B12 status, while a mathematical model of one-carbon metabolism suggests that formate levels are sensitive to riboflavin status.

MacMillan et al. (2017) shows that riboflavin-deficiency results in no change in plasma formate concentration contrary to the predictions of the mathematical model, while a 15% decrease in formate production was noted.

Contrary to our hypothesis, vitamin B12 deficient rats exhibited marked increases in formate production. This is likely due to impairment of oxidation of excess one-carbon units resulting in an increase of formate appearance.

Studies in fetal rats have shown plasma formate concentrations approximately 6-fold higher than those in adult rodents. Elevated formate levels persist from birth until approximately the time of weaning and are decreased to adult levels by 8 weeks of age. The slight increase in formate production rates observed in pregnant-female rats likely is not enough to contribute greatly to the increases in plasma formate observed in fetal rat pups. Analysis of the expression of key genes of one-carbon metabolism provides evidence that most this formate is produced in the fetal pups and not the mother.