A bicyclic amino acid to improve discriminations among transport systems.
A bicyclic amino acid to improve discriminations among transport systems.
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一种双环氨基酸，可改善运输系统之间的区别。
DOI：
10.1016/s0021-9258(18)91789-8
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发表时间：
1969
期刊：
影响因子：
--
通讯作者：
R. Zand
中科院分区：
文献类型：
--
作者：
H. Christensen;M. Handlogten;I. Lam;H. Tager;R. Zand
通过相应的螺乙内酰脲，将氨基和羧基引入到去甲樟脑的双环庚烷环的碳2上，产生了一种模型底物，其中严格指定的位置由对应于普通支链氨基酸的碳原子占据。该物质通过具有非极性（通常为分支）侧链的氨基酸系统在所有检测细胞和组织中转运。尚未观察到任何其他系统对其进行可测量的转运，各种红细胞和埃利希细胞的Na+依赖性系统已被明确排除在外。在非极性侧链氨基酸的Na+非依赖性转运中未检测到意外异质性。我们使用了另一种新的合成氨基酸来说明该物质如何与α-（甲氨基）-异丁酸结合使用，以确定给定氨基酸的运输途径。当用氨基腈代替双环氨基酸制备时，产物仅含31%（而不是用乙内酰脲得到的92%）的一般有效组分，这是用磺化聚苯乙烯树脂色谱法分离的。这两种组分被认为是内消旋异构体，尽管构象尚未确定。在这两种形式中，只有在树脂柱上迁移较慢的一种被大肠杆菌吸收，而另一种被用于支链氨基酸的系统吸收。同样的产物被人红细胞吸收的速度是异异构体的2.5倍，被鸽子红细胞吸收的速度是异异构体的3.7倍，在埃利希细胞中吸收的速度是异异构体的5倍。研究了B-2-氨基双环[2，2，1]庚烷-2-羧酸与大肠杆菌亮氨酸结合蛋白的结合。结果表明，该化合物对亮氨酸结合的抑制作用远弱于对亮氨酸转运的KmandKi值和对亮氨酸转运的抑制作用，该化合物对转运机制和相互作用有了新的认识，并有望有助于进一步区分转运系统和其他生物受体系统。活性异构体的绝对构型和构象的确定应有助于描述特定的转运受体位点，包括接受它的位点和排除它的位点。
Introduction of an amino and a carboxyl group onto carbon 2 of the bicycloheptane ring of norcamphor, by way of the corresponding spirohydantoin, produced a model substrate in which rigidly specified positions are taken by carbon atoms corresponding to those of the ordinary branched chain amino acids. This substance is transported by the system serving for amino acids with apolar (usually, branched) side chains in all cells and tissues tested. No measurable transport of it by any other system has yet been observed, the Na+-dependent systems of various erythrocytes and the Ehrlich cell having been specifically excluded. No unsuspected heterogeneity was detected in the Na+-independent transport of amino acids with apolar side chains by its use. We have used another new synthetic amino acid to illustrate how this substance can be used in conjunction with α-(methylamino)-isobutyric acid for determining by what routes a given amino acid is transported. When the bicyclic amino acid was prepared instead by way of the aminonitrile, the product contained only 31% (rather than the 92% obtained by way of the hydantoin) of the generally effective component, as separated by chromatography on sulfonated polystyrene resin. These two components are presumed to be theendoandexoisomers, although conformations have not yet been assigned. Of the two forms, only the one migrating more slowly on resin columns was taken up byEscherichia coliand that by the system serving for branched chain amino acids. The same product was taken up 2.5 times as fast by the human red blood cell, 3.7 times as fast by the pigeon red blood cell, and 5 times as fast in the Ehrlich cell, as theaisomer. The binding of b-2-aminobicyclo[2,2,1]heptane-2-carboxylic acid to the leucine-binding protein ofE. coliand its inhibition of the binding of leucine were far weaker than predicted from itsKmandKivalues for transport and inhibition of leucine transport.The bicyclic amino acid has permitted new discriminations of transport agencies and interactions, and may be expected to assist in the further discrimination of transport systems and other biological receptor systems. Determination of the absolute configuration and conformation of the active isomer should assist in the description of specific transport receptor sites, both that which accepts it and those that exclude it.