Christensen B, Guttormsen A B, Schneede J, Riedel B, Refsum H, Svardal A, Ueland P M
Department of Clinical Biology, Bergen, Norway.
Anesthesiology. 1994 May;80(5):1046-56. doi: 10.1097/00000542-199405000-00014.
Prolonged exposure to nitrous oxide causes adverse effects mimicking those of cobalamin deficiency. This is explained by irreversible oxidation of cobalamin bound to the enzyme methionine synthase. The inactivation of methionine synthase by nitrous oxide in cultured human fibroblasts is decreased at high concentrations of methionine in culture medium.
We investigated the possible protection against cobalamin inactivation by preoperative methionine loading in patients undergoing nitrous oxide anesthesia. Fourteen patients receiving anesthesia for 75-230 min were included. Half of these patients received a peroral methionine loading dose 2 h before anesthesia.
After nitrous oxide exposure, a considerable inactivation of methionine synthase in mononuclear white blood cells was seen in all patients, reaching a nadir after 5-48 h. In the patients not subjected to a methionine load, recovery of enzyme activity was not complete within 7 days. In the patients receiving a methionine load, the kinetics of inactivation of methionine synthase were similar, but the rate and extent of enzyme recovery was higher than in patients not receiving methionine, and 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 concentration was still increased (mean 28.7%) 7 days after anesthesia in the patients not receiving methionine. A marked peak in homocysteine concentration 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 blood cells, and the serum concentration of the cobalamin marker methylmalonic acid, were not altered after nitrous oxide anesthesia or methionine loading or both.
Our data suggest that short time exposure to nitrous oxide selectively impairs the function of the cobalamin-dependent methionine synthase. Furthermore, preoperative administration of methionine should be considered as a means to counteract adverse effects of nitrous oxide.
长期接触氧化亚氮会导致类似钴胺素缺乏的不良反应。这是由于与甲硫氨酸合酶结合的钴胺素发生不可逆氧化所致。在培养基中甲硫氨酸浓度较高时，培养的人成纤维细胞中氧化亚氮对甲硫氨酸合酶的失活作用会减弱。
我们研究了在接受氧化亚氮麻醉的患者中，术前给予甲硫氨酸负荷是否可能预防钴胺素失活。纳入了14例接受75 - 230分钟麻醉的患者。其中一半患者在麻醉前2小时口服甲硫氨酸负荷剂量。
氧化亚氮暴露后，所有患者单核白细胞中的甲硫氨酸合酶均出现明显失活，在5 - 48小时后达到最低点。未接受甲硫氨酸负荷的患者，酶活性在7天内未完全恢复。接受甲硫氨酸负荷的患者，甲硫氨酸合酶失活的动力学相似，但酶恢复的速率和程度高于未接受甲硫氨酸的患者，且有4例患者的酶活性甚至超过术前水平。甲硫氨酸合酶的失活与血浆同型半胱氨酸短暂升高有关，未接受甲硫氨酸的患者在麻醉7天后同型半胱氨酸浓度仍升高（平均升高28.7%）。在接受甲硫氨酸负荷的患者中，麻醉后立即观察到同型半胱氨酸浓度明显峰值，但7天后同型半胱氨酸水平仍升高（平均升高30.5%）。氧化亚氮麻醉或甲硫氨酸负荷或两者同时作用后，单核白细胞中另一种钴胺素依赖性酶——甲基丙二酰辅酶A变位酶的活性以及钴胺素标志物甲基丙二酸的血清浓度均未改变。
我们的数据表明，短时间接触氧化亚氮会选择性损害钴胺素依赖性甲硫氨酸合酶的功能。此外，术前给予甲硫氨酸应被视为抵消氧化亚氮不良反应的一种方法。
