Formate metabolism in the rat

Abstract

The folate-associated one-carbon (1C) metabolic pathways provide the building blocks for key components of DNA (thymidylate and purines), as well as the supply of methyl groups for methyltransferases. The free formate pool plays an essential role in the transport of one-carbon units from production to utilization. An enzymatic assay was optimized for the determination of the plasma formate concentration in rats under normal and folate-deficient conditions. Stable isotope tracer infusions were used to quantify the endogenous production rates of formate; this amounted to 75 μmol/hr /100 g body weight in folate-replete rats, dropping to 45 μmol/hr /100 g body weight in folate-deficient rats. This means that, in (healthy) folate-replete rats, endogenous formate production accounts for -35% of the total ingested potential 1C groups (44% of that remaining after accounting for net protein synthesis). This could indicate that formate production is a central component of the metabolism of some of these 1C precursors. We investigated the importance of known dietary 1C precursors to the 1C pool through a dietary precursor supplementation study. Serine, histidine, and choline were found to be significant precursors to formate.