d-amino acids are now recognized to be widely present in organisms and play essential roles in biological processes. Some d-amino acids are metabolized by d-amino acid oxidase (DAO), while d-Asp and d-Glu are metabolized by d-aspartate oxidase (DDO). In this study, levels of 22 amino acids and the enantiomeric compositions of the 19 chiral proteogenic entities have been determined in the whole brain of wild-type ddY mice (ddY/DAO^+/+), mutant mice lacking DAO activity (ddY/DAO^−/−), and the heterozygous mice (ddY/DAO^+/−) using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No significant differences were observed for l-amino acid levels among the three strains except for l-Trp which was markedly elevated in the DAO^+/− and DAO^−/− mice. The question arises as to whether this is an unknown effect of DAO inactivity. The three highest levels of l-amino acids were l-Glu, l-Asp, and l-Gln in all the three strains. The lowest l-amino acid level was l-Cys in ddY/DAO^+/− and ddY/DAO^−/− mice, while l-Trp showed the lowest level in ddY/DAO^+/+mice. The highest concentration of d-amino acid was found to be d-Ser, which also had the highest % d value (~ 25%). d-Glu had the lowest % d value (~ 0.01%) in all the three strains. Significant differences of d-Leu, d-Ala, d-Ser, d-Arg, and d-Ile were observed in ddY/DAO^+/− and ddY/DAO^−/− mice compared to ddY/DAO^+/+ mice. This work provides the most complete baseline analysis of l- and d-amino acids in the brains of ddY/DAO^+/+, ddY/DAO^+/−, and ddY/DAO^−/− mice yet reported. It also provides the most effective and efficient analytical approach for measuring these analytes in biological samples. This study provides fundamental information on the role of DAO in the brain and may be relevant for future development involving novel drugs for DAO regulation.

d-氨基酸现已被认为广泛存在于生物体中，并在生物过程中起着至关重要的作用。某些d-氨基酸被d-氨基酸氧化酶（DAO）代谢，而d -Asp和d -Glu被d-天冬氨酸氧化酶（DDO）代谢。在这项研究中，已经确定了野生型ddY小鼠（ddY / DAO ^{+ / +}），缺乏DAO活性（ddY / DAO）的突变小鼠的全脑中22种氨基酸的水平和19种手性蛋白形成实体的对映体组成^-/-）和杂合子小鼠（ddY / DAO ^+/-）使用高效液相色谱-串联质谱（HPLC-MS / MS）。除了在DAO ^+/-和DAO ^-/-小鼠中明显升高的1- Trp外，在三个菌株中没有观察到1-氨基酸水平的显着差异。由此产生的问题是，这是否是DAO不活跃的未知结果。三个最高级别升的α-氨基酸是升-Glu，升-Asp，并升-Gln在所有三个菌株。在ddY / DAO ^+/-和ddY / DAO ^-/-小鼠中最低的l-氨基酸水平是l -Cys ，而l-Trp在ddY / DAO ^{+ / +}小鼠中显示最低水平。发现最高浓度的d-氨基酸为d- Ser，其d％值也最高（约25％）。在所有三个菌株中，d -Glu的％d值最低（〜0.01％）。与ddY / DAO ^{+ / +}小鼠相比，在ddY / DAO ^+/-和ddY / DAO ^-/-小鼠中观察到d -Leu，d -Ala，d -Ser，d -Arg和d -Ile的显着差异。这项工作为l-和d提供了最完整的基线分析尚未报道ddY / DAO ^{+ / +}，ddY / DAO ^+/-和ddY / DAO ^-/-小鼠大脑中的氨基酸。它还为测量生物样品中的这些分析物提供了最有效的分析方法。这项研究提供了有关DAO在大脑中的作用的基本信息，并且可能与涉及DAO调节新药的未来发展有关。