Graduate School of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 1;879(29):3162-8. doi: 10.1016/j.jchromb.2011.06.028. Epub 2011 Jun 22.
It was believed for long time that d-amino acids are not present in mammals. However, current technological advances and improvements in analytical instruments have enabled studies that now indicate that significant amounts of D-amino acids are present in mammals. The most abundant D-amino acids are D-serine and D-aspartate. D-Serine, which is synthesized by serine racemase and is degraded by D-amino-acid oxidase, is present in the brain and modulates neurotransmission. D-Aspartate, which is synthesized by aspartate racemase and degraded by D-aspartate oxidase, is present in the neuroendocrine and endocrine tissues and testis. It regulates the synthesis and secretion of hormones and spermatogenesis. D-Serine and D-aspartate bind to the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors and function as a coagonist and agonist, respectively. The enzymes that are involved in the synthesis and degradation of these D-amino acids are associated with neural diseases where the NMDA receptors are involved. Knockout mice for serine racemase and D-aspartate oxidase have been generated, and natural mutations in the d-amino-acid oxidase gene are present in mice and rats. These mutant animals display altered behaviors caused by enhanced or decreased NMDA receptor activity. In this article, we review currently available studies on D-amino acid metabolism in mammals and discuss analytical methods used to assay activity of amino acid racemases and D-amino-acid oxidases.
长期以来，人们一直认为哺乳动物体内不存在 D-氨基酸。然而，当前技术的进步和分析仪器的改进，使得人们现在可以进行研究，表明哺乳动物体内确实存在大量的 D-氨基酸。最丰富的 D-氨基酸是 D-丝氨酸和 D-天冬氨酸。D-丝氨酸由丝氨酸消旋酶合成，被 D-氨基酸氧化酶降解，存在于大脑中，调节神经递质传递。D-天冬氨酸由天冬氨酸消旋酶合成，被 D-天冬氨酸氧化酶降解，存在于神经内分泌和内分泌组织以及睾丸中。它调节激素的合成和分泌以及精子发生。D-丝氨酸和 D-天冬氨酸与 N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体结合，分别作为共激动剂和激动剂发挥作用。参与这些 D-氨基酸合成和降解的酶与 NMDA 受体有关的神经疾病有关。已经生成了丝氨酸消旋酶和 D-天冬氨酸氧化酶的敲除小鼠，并且在小鼠和大鼠中存在 d-氨基酸氧化酶基因的天然突变。这些突变动物表现出 NMDA 受体活性增强或减弱引起的行为改变。本文综述了目前关于哺乳动物 D-氨基酸代谢的研究，并讨论了用于检测氨基酸消旋酶和 D-氨基酸氧化酶活性的分析方法。
