Formate metabolism in vivo in folate-deficient rats
The production of formate is a major, though understated, motif in metabolism. Formate may arise from amino acid metabolism (serine, glycine, histidine, tryptophan, and methionine), from demethylation reactions, as well as the catabolism of choline and methanol. The concentration of plasma formate is approximately 50 μM in healthy rats. We have shown that plasma and urine formate concentrations are increased up to 6-fold in folate-deficient rats, and may be a useful marker for remethylation defects. The origins of this excess formate are examined further through targeted diet experiments using known and suspected one-carbon precursors. Upon investigating formate turnover, we find that folate-deficient rats have a substantially lower rate of endogenous formate production compared to folate-sufficient rats (43±4 vs. 76±16 umol/hr/100g ,P<0.001). This decreased rate of formate production in the face of elevated formate concentration implies an appreciable impairment in formate removal. In folate-sufficient rats, formate production amounts to 40% of the total potential one-carbon groups generated from the diet. Further work will continue to elucidate this important aspect of nutrition.