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D-Serine Usage And Synthesis
Overview D-serine is the D-form of the amino acid serine, but is not used for the protein synthesis. Amino acids are among the most significant molecules in nature and exist in an l- and a d-form. The chemical and physical properties of l- and d-amino acids are enormously similar except for their optical characteristics[1]. During the emergence of life, only the l-amino acids were selected for the formation of polypeptides and proteins. Amino acids are not present in mammals and that d-amino acids were restricted to some bacteria and insects. Only a few decades ago, it was largely believed that free d- amino acids are not present in mammals and that d-amino acids were restricted to some bacteria and insects. Often, d-amino acids were called “unnatural” amino acids and they were considered to be the by-products of microorganisms metabolism.
The first report to show the presence of substantial quantities of free d-amino acids in mammalian tissues was by dunlop et al 1986 where, surprisingly, a large amount of d-aspartic acid[d- asp] in the cerebrum of a newborn rat and in the pituitary gland of an adult rat was reported[2]. A second d-amino acid, d-serine, was then identified in considerable amounts in the brains of rodents and man[3, 4]. Successive studies verified that some d- amino acids exist in the mammalian central nervous system(CNS) and peripheral tissues in, unpredictably, high concentrations that may exceed the level of l-amino acids occurrence[4]. The unanticipated detection of large amounts of endogenous d-serine in the brain, by hashimoto et al, initiated a series of studies from several laboratories that investigated the physiological role of endogenous d-serine. Recently endogenous d-serine has been associated with several physiological and pathological n-methyl-d-aspartate receptor(NMDAR)-reliant processes, including NMDAr transmission and synaptic plasticity[5-7], cell migration, and neurotoxicity[8-10].
Figure 1 the chemical structure of D-serine
Localization The distribution of d-serine is parallel to the distribution of nMda type glutamate receptors[4]. D-Serine has been detected at relatively high levels in certain areas in the adult brain with particularly high levels of nMdars, including cerebral cortex, hippocampus, thalamus, hypothalamus, amygdala, and retina. Nonetheless, brain regions, such as the hindbrain, pons, and medulla have nearly imperceptible levels of d-serine. Significantly, it has been demonstrated that d-serine is localized principally within glial cells[14, 5] in the retina, Stevens et al[4] reported the occurrence of d-serine in astrocytes and Mu?ller glia cells. Recently, several studies suggest that the synthesis, storage, and release of d-serine may not be limited exclusively to astrocytes, but rather may involve specific functions for certain cells[6].