Determination of α-aminoadipic acid in brain, peripheral tissues, and body fluids using GC/MS with negative chemical ionization
Determination of α-aminoadipic acid in brain, peripheral tissues, and body fluids using GC/MS with negative chemical ionization
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DOI：
10.1016/j.molbrainres.2003.08.004
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发表时间：
2003-10-21
期刊：
影响因子：
--
通讯作者：
Schwarcz, R
中科院分区：
文献类型：
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作者：
Guidetti, P;Schwarcz, R
α-氨基己二酸（alphaAA）是兴奋性氨基酸谷氨酸的结构同系物，是哺乳动物细胞中赖氨酸代谢的天然产物。在实验条件下，aAA可以影响各种元素的多巴胺能神经传递。此外，作为犬尿氨酸氨基转移酶II的选择性抑制剂，α AA能够降低脑中神经抑制代谢物犬尿烯酸的水平。现在，我们描述了这种潜在的内源性神经调质在组织和体液的气相色谱/质谱（GC/MS）分析其五氟苄基（PFB）衍生物的鉴定。从GC柱中回收α AA，保留时间约为7 min。随后使用负离子化电子捕获的MS分析显示α AA有两个单独的离子（m/z 520，约为45%，m/z 322，约为55%）。这两种离子都用两种不同的GC方法进行了鉴定。在大鼠中，不同脑区的alphaAA水平范围为5 - 30 μ M，外周器官为8 - 40 μ M，而血清和尿液中仅含有1-2 μ M alphaAA。人脑中的水平为18.7 +/- 2.4 μ M（皮质）和18.0 +/- 1.7 μ M（纹状体）α AA（各n = 9），小鼠前脑含有8.3 +/- 1.9 μ M α AA（n = 6）。纹状体内注射NMDA（300 nmol/2.5穆尔）引起的大鼠神经元耗竭并没有改变纹状体中α AA的含量，表明脑α AA至少部分存在于神经胶质细胞中。因此，α AA可以作为兴奋性神经传递的神经胶质源性调节剂发挥作用。(C)2003 Elsevier B. V.保留所有权利。
alpha-Aminoadipic acid (alphaAA) is a structural homolog of the excitatory amino acid glutamate and a natural product of lysine metabolism in mammalian cells. Under experimental conditions, aAA can influence various elements of glutamatergic neurotransmission. Moreover, as a selective inhibitor of kynurenine aminotransferase II, alphaAA is capable of decreasing the levels of the neuroinhibitory metabolite kynurenic' acid in the brain. We now describe the identification of this potential endogenous neuromodulator in tissues and body fluids by gas chromatography/mass spectrometry (GC/MS) analysis of its pentafluorobenzyl (PFB) derivative. alphaAA was recovered from the GC column with a retention time of similar to 7 min. Subsequent MS analysis using electron capture with negative ionization revealed two separate ions for alphaAA (m/z 520, similar to 45% and m/z 322, similar to 55%). Both of these ions were positively identified with two different GC methodologies. In the rat, alphaAA levels ranged from 5 to 30 muM in various brain areas and from 8 to 40 muM in peripheral organs, whereas serum and urine contained only 1-2 muM alphaAA. Levels in the human brain were 18.7 +/- 2.4 muM (cortex) and 18.0 +/- 1.7 muM (striatum) alphaAA (n = 9 each), and the mouse forebrain contained 8.3 +/- 1.9 muM alphaAA (n = 6). Neuronal depletion, caused in rats by an intrastriatal injection of NMDA (300 nmol/2.5 mul), did not alter the striatal content of alphaAA, indicating that brain alphaAA resides at least in part in glial cells. alphaAA may therefore function as a glia-derived modulator of excitatory neurotransmission. (C) 2003 Elsevier B.V. All rights reserved.