Formate: a key metabolite for the fetus and neonatal animal (827.5)

Abstract

One‐carbon metabolism, mediated by tetrahydrofolate (THF), is critical for nucleotide synthesis and for methylation reactions, including DNA methylation and the synthesis of small molecules such as creatine and phosphatidylcholine. In addition to one‐carbon groups carried by THF it is apparent that formate is also a key intermediate in one‐carbon metabolism. Produced within mitochondria, formate is released to the cytosol, and incorporated into 10‐formyl‐THF where it may be directly used for purine synthesis or converted to more reduced forms for thymidylate synthesis and for the methylation of homocysteine to methionine. We employed a GC/MS, isotope dilution assay to measure formate levels in situations of rapid growth and development. Plasma [formate] was ~40 uM in adult rats; however, levels of ~400 uM were evident in neonatal (2‐3 days old) rats, declining to adult levels at about 56 days. Plasma [formate] was ~10 uM in non‐pregnant ewes; this increases to ~40 uM during pregnancy. Much higher levels were found in plasma from fetal lambs and amniotic fluid (116‐121 days gestation). We suggest that these data point to a key role for formate in growing organisms, possibly in distributing one‐carbon groups to different organs. (Supported by CIHR, RDC).Grant Funding Source: CIHR, RDC