D-Amino Acids in the Nervous and Endocrine Systems

Figure 2

Activation of the N-methyl-D-aspartate (NMDA) receptor by D-cysteine. D-Cysteine is one of the sources of H₂S in the brain. D-Cysteine is converted to 3-mercaptopyruvate (3MP) by D-amino acid oxidase (DAO). 3MP is then degraded by 3-mercaptopyruvate sulfurtransferase (3MST) to generate H₂S in the neurons. Hydrogen polysulfides (H₂; –5) are also generated by 3MST from 3MP. H₂S reduces the disulfide bonds in the NMDA receptor and increases the activity of the NMDA receptor. H₂ also activates the transient receptor potential (TRP) A1 channel. Activated TRPA1 channel induces Ca²⁺ influx, leading to D-serine release in astrocytes, and D-serine then activates the NMDA receptor.