The effect of nitrous oxide-induced vitamin B12 deficiency on in vivo folate metabolism

The effect of N₂O-induced vitamin B₁₂ deficiency on $\text{in}\text{vivo}$ folate metabolism was studied in an animal model previously developed for studies of the folate enterohepatic cycle, and in rats with localized, subcutaneous tumor nodules. While N₂O inhibited liver folate polyglutamate formation, it did not affect the absorption of (³H)PteGlu₁ from the gut, its reduction, methylation, and transport to the liver, or the subsequent secretion of CH₃H₄(³H)PteGlu₁ into bile—the folate enterohepatic cyle. In addition, N₂O did not impair folate polyglutamate formation in the fibrosarcoma tumor nodule suggesting that tumor tissue can either demethylate CH₃H₄PteGlu₁ by an alternate pathway or can utilize it as a substrate for polyglutamate formation without demethylation.