Pegg A E, Seely J, Zagon I S
Science. 1982 Jul 2;217(4554):68-70. doi: 10.1126/science.6806900.
alpha-Difluoromethylornithine is an enzyme-activated irreversible inhibitor of ornithine decarboxylase that forms a covalent bond with the enzyme. When alpha-[5-14C]difluoromethylornithine was administered to androgen-treated mice, only ornithine decarboxylase became labeled. Autoradiographic examination of kidney, liver, and brain indicated much more extensive incorporation of labeled difluoromethylornithine into kidney protein than into the protein of the other tissues. Such incorporation was greatly reduced by prior treatment of the mice with cycloheximide. These results correlate with the presence of ornithine decarboxylase activity which is much higher in the kidney than in the other tissues and is lost rapidly when protein synthesis is inhibited. The binding of this drug in vivo, therefore, is useful for determining the distribution of ornithine decarboxylase. The enzyme was predominantly located in the proximal tubule cells of the kidney in androgen-treated mice.
α-二氟甲基鸟氨酸是鸟氨酸脱羧酶的一种酶激活不可逆抑制剂,它与该酶形成共价键。当给用雄激素处理过的小鼠施用α-[5-¹⁴C]二氟甲基鸟氨酸时,只有鸟氨酸脱羧酶被标记。对肾脏、肝脏和大脑进行放射自显影检查表明,标记的二氟甲基鸟氨酸掺入肾脏蛋白质的程度比掺入其他组织蛋白质的程度广泛得多。在用环己酰亚胺预先处理小鼠后,这种掺入大大减少。这些结果与鸟氨酸脱羧酶活性的存在相关,该酶在肾脏中的活性比在其他组织中高得多,并且在蛋白质合成受到抑制时会迅速丧失。因此,这种药物在体内的结合对于确定鸟氨酸脱羧酶的分布很有用。在用雄激素处理过的小鼠中,该酶主要位于肾脏的近端小管细胞中。