PREOPERATIVE METHIONINE LOADING ENHANCES RESTORATION OF THE COBALAMIN-DEPENDENT ENZYME METHIONINE SYNTHASE AFTER NITROUS-OXIDE ANESTHESIA

Background: Prolonged exposure to nitrous oxide causes adverse effects mimicking those of cobalamin deficiency. This is explained by irrever sible oxidation of cobalamin bound to the enzyme methionine synthase. The inactivation of methionine synthase by nitrous oxide in cultured h uman fibroblasts is decreased at high concentrations of methionine in culture medium. Methods: We investigated the possible protection again st cobalamin inactivation by preoperative methionine loading in patien ts undergoing nitrous oxide anesthesia. Fourteen patients receiving an esthesia for 75-230 min were included. Half of these patients received a peroral methionine loading dose 2 h before anesthesia. Results: Aft er nitrous oxide exposure, a considerable Inactivation of methionine s ynthase in mononuclear white blood cells was seen in all patients, rea ching a nadir after 5-48 h. In the patients not subjected to a methion ine load, recovery of enzyme activity was not complete within 7 days. In the patients receiving a methionine load, the kinetics of inactivat ion of methionine synthase were similar, but the rate and extent of en zyme recovery was higher than in patients not receiving methionine, an d in four patients, the enzyme activity even exceeded the preoperative level. The inactivation of methionine synthase was associated with a transient increase in plasma homocysteine, and the homocysteine concen tration was still increased (mean 28.7%)7 days after anesthesia in the patients not receiving methionine. A marked peak in homocysteine conc entration was observed immediately after anesthesia in the methionine- loaded patients, but the homocysteine level was still increased (mean of 30.5%) after 7 days. The activity of the other cobalamin-dependent enzyme, methylmalonyl coenzyme A mutase, in the mononuclear white bloo d cells, and the serum concentration of the cobalamin marker methylmal onic acid, were not altered after nitrous oxide anesthesia or methioni ne loading or both. Conclusions: Our data suggest that short time expo sure to nitrous oxide selectively impairs the function of the cobalami n-dependent methionine synthase. Furthermore, preoperative administrat ion of methionine should be considered as a means to counteract advers e effects of nitrous oxide.