IN VIVO F-19 NMR STUDIES OF THE METABOLISM OF FLUROINATED ANESTHETICS

肝脏是参与解毒的主要器官。 一系列的异生物物质 在过去十年中， 可以无创地监测器官的代谢 在麻醉的动物和人类中使用表面线圈NMR探针 其可以直接放置在感兴趣的组织上。使用 这种技术，异生物质的代谢转化， 在有利的情况下，可以直接观察到， 还可以研究细胞能量代谢和氧化还原化学。 利用这种技术，我们进行了代谢的研究， 几种氟化吸入麻醉剂， 更好地了解毒副作用的基础， 伴随着许多这些化合物的使用。 这些研究表明， 第一次明确地确认了 作为麻醉剂代谢物的甲氧基二氟乙酸盐 甲氧氟烷。 此外，我们还采用了这种技术， 直接甲基转移反应的研究 通过（甲基-2H3）甲硫氨酸的氘NMR观察。 这是 发现过量的蛋氨酸主要通过最初的 将甲基转移至甘氨酸以产生N-甲基甘氨酸 （肌氨酸），其随后在胰蛋白酶中处理。 这种甘氨酸/肌氨酸穿梭体的活性受以下因素的影响： 包括蛋氨酸在内的多种化学物质的干扰 类似物乙醇胺以及苯甲酸钠。 外贸 氘代D-甲硫氨酸表明其类似物通过 首先通过D-氨基酸氧化酶进行氧化脱氨，然后 转氨以产生L-甲硫氨酸，其通过 甘氨酸甲基转移酶。

The liver is the principal organ involved in the detoxification of a broad range of xenobiotics. During the past decade, it has become possible to monitor the metabolism of organs non-invasively in anesthetized animals and humans using surface coil NMR probes which can be placed directly over the tissue of interest. Using this technique, the metabolic transformations of xenobiotics can, in favorable cases, be directly observed, and perturbations of cellular energy metabolism and redox chemistry can also be studied. Using this technique, we have carried out studies of metabolism of several fluorinated inhalation anesthetics in order to obtain a better understanding of the basis for the toxic side effects which accompany the use of many of these compounds. These studies ave provided the first unequivocal identification of methoxydifluoroacetate as a metabolite of the anesthetic methoxyflurane. Additionally, we have adapted this technique to the study of transmethylation reactions based on direct observations by deuterium NMR of (methyl-2H3)methionine. It was found that excess methionine s metabolized largely via the initial transfer of the methyl group to glycine to yield N-methylglycine (sarcosine), which is subsequently processed in the mitochondrion. The activity of this glycine/sarcosine shuttle is subject to interference by a number of chemicals including the methionine analog ethionine, as well as sodium benzoate. Studies with deuterated D-methionine indicate that his analog is metabolized via initial oxidative deamination by D-amino acid oxidase, then transaminated to yield L-methionine which is the metabolized via glycine N-methyltransferase.