d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.
d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.
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DOI：
10.1021/acschemneuro.6b00398
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发表时间：
2017-06-21
影响因子：
5
通讯作者：
Armstrong DW
中科院分区：
文献类型：
--
作者：
Weatherly CA;Du S;Parpia C;Santos PT;Hartman AL;Armstrong DW
L-对映体是所有生命系统中的主要氨基酸类型。然而，D-氨基酸，曾经被认为是“非天然的”，已被发现是本土的，甚至在哺乳动物系统中，越来越多地出现在基本的生物和神经功能的作用。报告了来自NIH Swiss小鼠的海马、皮质和血液样品中的D-和L-氨基酸水平。首次分析了灌注脑组织，从而消除了内源性血液所致的伪影，并降低了氨基酸水平的小鼠间变异性。脑组织中的总氨基酸水平（L-加D-对映体）比血液中高10倍。然而，脑组织中所有测量的D-氨基酸水平通常比血液水平高约10至2000倍。与海马体相比，皮质中几乎所有测量的D-氨基酸水平都降低了13%。氨基酸的普遍性与其D-对映体形式的百分比之间存在近似的反比关系。有趣的是，谷氨酸与所有其他氨基酸不同，其D-对映体没有可量化的水平。这种D-氨基酸独特而明显的缺失/去除的生物神经学原因尚不清楚。然而，结果表明，D-谷氨酸代谢可能是一个单向的过程，而不是一个周期，根据L-谷氨酸/谷氨酰胺循环。结果提示哺乳动物脑中可能存在未报道的D-氨基酸消旋酶。特定的其他D-氨基酸的调节和功能进行了讨论。
The L-enantiomer is the predominant type of amino acid in all living systems. However, D-amino acids, once thought to be “unnatural”, have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both D- and L-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (L-plus D-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured D-amino acid levels in brain tissue are typically ~10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured D-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its D-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its D-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this D-amino acid is yet unknown. However, results suggest that D-glutamate metabolism is likely a unidirectional process and not a cycle, as per the L-glutamate/glutamine cycle. The results suggest that there might be unreported D-amino acid racemases in mammalian brains. The regulation and function of specific other D-amino acids are discussed.