Weatherly Choyce A, Du Siqi, Parpia Curran, Santos Polan T, Hartman Adam L, Armstrong Daniel W
Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019, United States.
Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, Maryland 21287, United States.
ACS Chem Neurosci. 2017 Jun 21;8(6):1251-1261. doi: 10.1021/acschemneuro.6b00398. Epub 2017 Feb 16.
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.
L-对映体是所有生物系统中主要的氨基酸类型。然而，曾经被认为是“非天然”的D-氨基酸，现已发现即使在哺乳动物系统中也是原生存在的，并且越来越多地显示出在重要的生物学和神经学功能中发挥作用。本文报道了来自美国国立卫生研究院（NIH）瑞士小鼠的海马体、皮质和血液样本中的D-和L-氨基酸水平。首次对灌注的脑组织进行了分析，从而消除了内源性血液引起的假象，并降低了小鼠之间氨基酸水平的差异。脑组织中的总氨基酸水平（L-和D-对映体之和）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-氨基酸水平降低了13%。氨基酸的普遍程度与其D-对映体形式的百分比之间存在近似反比关系。有趣的是，与所有其他氨基酸不同，谷氨酸没有可量化的D-对映体水平。这种D-氨基酸独特且明显缺失/去除的生物神经学原因尚不清楚。然而，结果表明，与L-谷氨酸/谷氨酰胺循环不同，D-谷氨酸代谢可能是一个单向过程，而非循环过程。结果表明，哺乳动物大脑中可能存在未被报道的D-氨基酸消旋酶。本文还讨论了其他特定D-氨基酸的调节和功能。
