Abstract

Formate is oxidized to CO 2 in the rat by folate-dependent reactions. Nitrous oxide treatment inhibited hepatic methionine synthetase activity, reduced hepatic S-adenosyl- l-methionine (Ado-Met) and tetrahydrofolate (H 4 folate) concentrations and decreased the rate of formate oxidation in the rat. The administration of methionine to nitrous oxide-treated rats increased hepatic Ado-Met concentrations and restored hepatic H 4folate levels and formate oxidation to control values but did not reverse the inhibition of methionine synthetase. Positive correlations were observed between hepatic Ado-Met levels and H 4folate concentrations and between hepatic H 4folate concentrations and formate oxidation. These results suggest that alterations in hepatic H 4folate concentrations may profoundly influence the oxidation of one-carbon compounds. They confirm the importance of the methionine synthetase reaction as a major source of regeneration of H 4folate. These findings also indicate that methionine acts at a site other than the methionine synthetase reaction to restore hepatic H 4folate concentrations and formate oxidation to control values in nitrous oxide-treated rats.

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