Garbow J R, Ridley W P, Bork V, Pan Y, Schaefer J
Monsanto Company, St. Louis, MO 63198.
Drug Metab Dispos. 1994 Mar-Apr;22(2):298-303.
The metabolism of 13C- and 15N-labeled milacemide, 2-(pentylamino)-acetamide, has been studied in rat liver and brain slices using solid-state NMR. This analysis is fast and efficient and can be used to monitor both major and minor metabolic pathways in mammalian tissue culture. The NMR work reported herein involves both conventional cross-polarization magic-angle spinning 13C and 15N NMR spectra and rotational-echo double resonance 13C-15N experiments. The latter measure quantitatively the breaking of isotopically labeled carbon-nitrogen chemical bonds. Our results, which are consistent with suggestions from previous metabolic studies, show that the first step in the breakdown of milacemide is the breaking of the pentylamine nitrogen bond to yield pentanoic acid and glycinamide. Total incorporation of 15N label from the resulting glycinamide fragment is comparable in rat liver and brain. In both tissues, considerably more of the 15N label from glycinamide is incorporated than the corresponding 13C label. Differences between the liver and brain tissue are also observed, with more synthesis incorporating the 13C labels taking place in the liver.
利用固态核磁共振技术，对13C和15N标记的米拉醋胺（2 - 戊基氨基乙酰胺）在大鼠肝脏和脑切片中的代谢情况进行了研究。该分析快速且高效，可用于监测哺乳动物组织培养中的主要和次要代谢途径。本文报道的核磁共振研究工作涉及传统的交叉极化魔角旋转13C和15N核磁共振谱以及旋转回波双共振13C - 15N实验。后者定量测量同位素标记的碳 - 氮化学键的断裂情况。我们的结果与先前代谢研究的推测一致，表明米拉醋胺分解的第一步是戊胺氮键的断裂，生成戊酸和甘氨酰胺。大鼠肝脏和脑中，来自所得甘氨酰胺片段的15N标记的总掺入量相当。在这两种组织中，甘氨酰胺中15N标记的掺入量都比相应的13C标记多得多。同时也观察到肝脏和脑组织之间的差异，肝脏中发生的掺入13C标记的合成反应更多。
