Evidence for inhibition of exodus of small neutral amino acids from non-brain tissues in hyperphenylalaninaemic rats.
Evidence for inhibition of exodus of small neutral amino acids from non-brain tissues in hyperphenylalaninaemic rats.
复制标题
抑制高苯丙氨酸血症大鼠非脑组织中小中性氨基酸外流的证据。
DOI：
10.1007/bf01800722
复制
发表时间：
1989
影响因子：
4.2
通讯作者：
Christensen,HN
中科院分区：
文献类型：
--
作者：
deCespedes,C;Thoene,JG;Lowler,K;Christensen,HN
PKU中几种血浆氨基酸耗竭的机制仍未得到解释。在本研究中，断奶大鼠腹腔注射Phe 2 h后，血浆中几种氨基酸浓度有统计学意义的下降。这种模式与在PKU患者中观察到的非常相似。肝/血浆分布比，主要是肌肉/血浆分布比，在大多数情况下都有统计学意义上的显著增加，并伴有相应的血浆浓度下降。在非胰岛素原性转运系统L类似物（2 -氨基-降冰片烷- 2 -羧酸的a（±）异构体）的相同条件下，等量注射产生的Ala和Gly的分布比在统计上显著增加，并且可能在肌肉中增加Pro，以及在肝脏中增加Ala。这些结果似乎表明，获得的高细胞内Phe抑制了通过系统L的小中性氨基酸的外流，导致它们在血浆中并最终在大脑中耗竭。这种效应可能与苯丙氨酸抑制大体积中性氨基酸进入血脑屏障水平有关。需要进一步的研究来评估这些影响与PKU的相关性。
The mechanism of the depletion of several plasma amino acids in PKU has remained unexplained. In the present study, a statistically significant decrease in the plasma concentration of several amino acids was observed 2 h after the intraperitoneal injection of Phe to weanling rats. The pattern was very similar to the one observed in PKU patients. Statistically significant increases in the distribution ratios liver/plasma and, mainly, muscle/plasma ratios accompanied in most of the cases the corresponding decreases in plasma concentrations. Equimolar injection under the same conditions of the non‐insulinogenic transport system L analogue, the a(±) isomer of the 2‐amino‐norbornane‐2‐carboxylic acid, produced, in a parallel effect to Phe, statistically significant increases in the distribution ratios of Ala and Gly, and probably of Pro in muscle, as well as of Ala in liver. These results seem to indicate that the high intracellular Phe attained inhibits the exodus of small neutral amino acids through system L, causing their depletion in plasma and ultimately in the brain. This effect may be additive to the inhibition by Phe of the entry of bulky neutral amino acids at the level of the blood‐brain barrier. Further study is needed to assess the relevance of these effects to PKU.