Polyglutamate forms of folate in resting and proliferating mammalian tissues.

1. Tritiated folic acid (pteroylglutamic acid) was injected into rats whose livers were undergoing regeneration after partial hepatectomy, and into normal control rats. 2. The major form of labelled liver folate was found to be pteroylpentaglutamate in both hepatectomized and normal rats and there was no difference in the proportion of pteroylpentaglutamate to other forms of folate in the regenerating or resting liver. 3. Folate concentrations were also measured in leucocytes from normal and leukaemic patients. 4. Pteroylpolyglutamates constituted the main form of folate in both sets of cells. There was again no difference in proportion of pteroylpolyglutamate to pteroylmonoglutamate forms of folate between normal mature cells and primitive blast cells. 5. It is therefore suggested that pteroylpolyglutamates, which constitute nearly all the folates in cells actively synthesizing DNA and protein as well as in resting cells, probably act as the coenzymes in vivo for the folate-dependent reactions in DNA, RNA and protein synthesis in mammalian systems.