NITROUS-OXIDE PROVOKES CHANGES IN FOLYLPENTAGLUTAMATES AND HEXAGLUTAMATES

Liver folates isolated from rats fed a control diet consisted of H4PteGlu5 (44% of total) and 5-methyl-H4PteGlu5 (19%) with smaller amounts of 10-formyl-H4PteGlu5 (13%), H4PteGlu6 (13%), 10-formyl-H4PteGlu6 (4%) and 5-methyl-H4PteGlu6 (2%). Folates from methionine-deficient rats contained more nearly equal amounts, on a molar basis, of folylpenta- and hexaglutamates, and hence these were more suitable subjects for comparing the metabolism of these compounds in vivo. Livers from methionine-deficient rats contained H4PteGlu5 (30%), 5-methyl-H4PteGlu5 (13%), 10-formyl-H4PteGlu5 (10%), H4PteGlu6 (22%), 5-methyl-H4PteGlu6 (9%) and 10-formyl-H4PteGlu6 (11%). With exposure to N2O, 5-methyl-H4PteGlu5 (and 6) increased to 27% and 13%, respectively, whereas H4PteGlu5 (and 6) decreased to 20% and 17%, respectively. Nitrous oxide (N2O) perturbed both the penta- and hexaglutamates; the effect was somewhat more pronounced with the pentaglutamates. The partial depletion in tissue H4PteGlu(n) with N2O treatment helps explain the concomitant inhibition of the oxidation of [ring-14C]histidine, an event dependent on tetrahydrofolates.