D-Amino Acids in the Nervous and Endocrine Systems

Figure 1

The synthesis of D-serine in the central nervous systems (CNS). D-Serine is synthesized by serine racemase (SR). SR is inhibited by its translocation from the cytosol to a membrane, such as the endoplasmic reticulum (ER) or plasma membranes, all of which contain phosphatidylinositol 4,5-bisphosphate (PIP₂). F-box only protein 22 (FBXO22) interacts with SR and activates SR by preventing it from binding to the ER membrane. In astrocytes, glutamate receptor interacting protein 1 (GRIP1) binds to the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor and GRIP1 is then released from the AMPA receptor following stimulation with L-glutamate. Released GRIP1 activates SR. Protein interacting with C-kinase (PICK1) binds to erythropoietin-producing hepatocellular receptor (Eph)B3 or EphA4 in the astrocytes. PICK1 is released after ephrinB3 on the neurons interacts with the EphB3 or EphA4 receptor and then activates SR. Stargazin forms a complex with the AMPA receptor, postsynaptic density protein 95 (PSD-95), and SR and inhibits the activity of SR by promoting membrane localization in neurons. After the AMPA receptor is activated, SR is released from the plasma membrane, resulting in the activation of SR. The N-methyl-D-aspartate (NMDA) receptor is activated by glutamate and D-serine.