Formate provides new insights into folate-mediated one-carbon metabolism.

Vitamin B12 is though to be a co-factor in only two biochemical reactions in higher vertebrates. Provided the high complexity of absorption and transport systems that are associated with vitamin B12 metabolism, we proposed that this vitamin could be involved in other, yet to be discovered, reactions. To test this hypothesis, we carried out a 1H-NMR metabolomic analysis of sera from vitamin B12-deficient rats. In addition to the expected increases in methylmalonate and homocysteine (Hcy), we observed a sevenfold increase in formate levels in vitamin B12-deficient rats. This finding, however, does not involve a new enzyme as the elevation of formate can be attributed to secondary folate deficiency generally called the methyl-trap.

Formate and Hcy appear at two distant points in the folate-mediated one-carbon metabolism pathway and could be a valuable tool to obtain information on the integrity of that pathway. The effects of various B-complex vitamin deficiencies on formate and Hcy levels will be presented as well as a novel assay specifically developed to assay formate. Future directions will also be discussed.