Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier
Role of oxoproline in the regulation of neutral amino acid transport across the blood-brain barrier
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DOI：
10.1074/jbc.271.32.19129
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发表时间：
1996-08-09
影响因子：
4.8
通讯作者：
Vina, JR
中科院分区：
文献类型：
--
作者：
Lee, WJ;Hawkins, RA;Vina, JR
中性氨基酸通过易化转运系统L1穿过血脑屏障，其可允许需要的和不需要的氨基酸进入脑。钠依赖性氨基酸系统A和B-0，B-+仅位于近腔膜上，γ-谷氨酰转肽酶是γ-谷氨酰循环的第一种酶，它能将不需要的氨基酸泵出，是血脑屏障腔膜的一种组成蛋白。我们证明了γ-谷氨酰循环的细胞内产物氧代脯氨酸刺激钠依赖性系统A和B-o，B-+分别降低70%和20%。系统A的研究表明，2 mM的氧代脯氨酸增加其特异性底物N-甲基氨基异丁酸的亲和力50%。γ-谷氨酰循环和系统A转运的活性之间的这种关系可以提供短期调节机制，通过该机制可以延迟潜在有害氨基酸（即神经递质或其前体）的进入并加速其从脑中的去除。
Regulation of neutral amino acid transport was studied using isolated plasma membrane vesicles derived from the bovine blood-brain barrier, Neutral amino acids cross the blood-brain barrier by facilitative transport system L1, which may allow both desirable and undesirable amino acids to enter the brain, The sodium-dependent amino acid systems A and B-o,B-+ are located exclusively on abluminal membranes, in a position to pump unwanted amino acids out, gamma-Glutamyl transpeptidase, the first enzyme of the gamma-glutamyl cycle, is an integral protein of the luminal membrane of the blood-brain barrier, We demonstrate that oxoproline, an intracellular product of the gamma-glutamyl cycle, stimulates the sodium-dependent systems A and B-o,B-+ by 70 and 20%, respectively. Study of system A showed that 2 mM oxoproline increased the affinity for its specific substrate N-methylaminoisobutyrate by 50%. This relationship between the activity of the gamma-glutamyl cycle and system A transport may provide a short term regulatory mechanism by which the entry of potentially deleterious amino acids (i.e. neurotransmitters or their precursors) may be retarded and their removal from brain accelerated.