Formate metabolism in the folate‐deficient rat

Formate may arise from amino acid metabolism (serine, glycine, histidine, tryptophan, and methionine), from demethylation reactions, and methanol catabolism. Plasma [formate] is approximately 50 μM in rats. We have shown that plasma and urinary formate are increased up to 6‐fold in either folate‐deficient or Vitamin B12‐deficient rats, and may be a useful marker for remethylation defects. We therefore determined formate production rates in folate‐deficient and control rats. Rats were fed a folate‐deficient diet for 18 days; controls received a folate‐replete diet. Formate appearance was determined by means of a constant infusion of NaH13CO2. Plateau isotopic enrichment in formate was determined via GC‐MS. The rate of formate production in folate‐deficient rats was 43±4 umol/hr/100g compared to 76±16 umol/hr/100g for control rats (P<0.001). This decreased rate of formate production in the face of elevated [formate] implies an appreciable impairment in formate removal. In control rats, formate production amounted to 40% of the total potential one‐carbon groups generated from the diet. We conclude that formate production is a major, though unrecognized, motif in amino acid catabolism. Grant Funding Source : Canadian Institutes for Health Research and Memorial University of Newfoundland