Zhao N, Lo L C, Berova N, Nakanishi K, Tymiak A A, Ludens J H, Haupert G T
Department of Chemistry, Columbia University, New York, New York 10027, USA.
Biochemistry. 1995 Aug 8;34(31):9893-6. doi: 10.1021/bi00031a010.
The specific, high affinity binding of plant-derived digitalis glycosides by the mammalian sodium and potassium transporting adenosine triphosphatase (Na,K-ATPase, or sodium pump), a plasma membrane enzyme with critical physiological importance in mammalian tissues, has raised the possibility that a mammalian analog of digitalis might exist. We previously isolated and structurally characterized from bovine hypothalamus a novel isomer of the plant glycoside, ouabain, which differs structurally only in the attachment site and/or the stereochemistry of the steroid moiety [Tymiak et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8189-8193]. Hamlyn and co-workers reported a molecule purified from human plasma which by mass spectrometry could not be distinguished from plant ouabain [Hamlyn et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6259-6263]. Since rhamnoside cardiotonic steroids are not known as natural products from mammalian sources, it became important to compare these two pure isolates to determine if the same or structurally distinct compounds has been found. Our results indicate that the human and bovine Na,K-ATPase-inhibitors are identical, but different from plant ouabain. This supports the notion that the human sodium pump may be under specific physiological regulation by a mammalian analog of the digitalis glycosides.
哺乳动物钠钾转运三磷酸腺苷酶（Na，K - ATP酶，即钠泵）是一种在哺乳动物组织中具有关键生理重要性的质膜酶，它能与植物来源的洋地黄糖苷发生特异性、高亲和力结合，这引发了可能存在洋地黄类哺乳动物类似物的想法。我们之前从牛下丘脑分离并对植物糖苷哇巴因的一种新型异构体进行了结构表征，它在结构上仅在甾体部分的连接位点和/或立体化学上有所不同 [蒂米亚克等人（1993年）《美国国家科学院院刊》90，8189 - 8193]。哈姆林及其同事报道了从人血浆中纯化出的一种分子，通过质谱分析无法将其与植物哇巴因区分开来 [哈姆林等人（1991年）《美国国家科学院院刊》88，6259 - 6263]。由于鼠李糖苷强心甾体并非已知的哺乳动物来源天然产物，比较这两种纯分离物以确定是否发现了相同或结构不同的化合物变得很重要。我们的结果表明，人和牛的Na，K - ATP酶抑制剂是相同的，但与植物哇巴因不同。这支持了人类钠泵可能受到洋地黄糖苷类哺乳动物类似物特异性生理调节的观点。
