A Sparing Effect by Formate or Methanol on the Impairment of Creatine Metabolism in Folic Acid Deficiency

Abstract

IN a recent communication¹ we reported on an involvement of dietary folic acid and vitamin B₁₂ in creatine metabolism. The observations suggested that deficiencies of these vitamins were interfering with the economy of labile methyl groups. It has been established that the methyl groups of choline and methionine may undergo oxidative degradation to formate^2,3 and that the utilization of such metabolically derived formate for serine synthesis⁴ and possibly in other single-carbon addition reactions such as nucleic acid formation⁵ involves mediation of folic acid; this vitamin is also directly concerned with formate production from glycine⁶. It seemed possible, therefore, that the influence of folic acid on creatine formation might in part at least be due to a check on the drain of methyl to formate resulting in its increased availability for transmethylations (cf. ref. 6). A direct proof of this postulate was sought in the studies reported here on the influence by mass effect of administered formate on in vitro and in vivo creatine synthesis in mice suffering from folic-acid deficiency and in normal mice. Methanol was also used in place of formate since it functions better (see ref. 2) in the reverse step of formate reduction to methyl^2,3.