D-Amino acid oxidase

D-amino acid oxidase (DAAO) is a peroxisomal FAD-dependent flavoenzyme that stereoselectively oxidizes neutral and polar D-amino acids, producing α-keto acids, ammonia, and H₂O₂^[1][2]. Mechanistically, DAAO regulates D-serine, a major NMDA receptor co-agonist, thereby linking D-amino acid metabolism to glutamatergic neurotransmission^[3]. In schizophrenia research, elevated DAAO activity and reduced D-serine availability support DAAO as an experimental target for restoring NMDA receptor function^[4][5]. Compared with D-aspartate oxidase (DDO), which degrades acidic D-amino acids such as D-aspartate, DAAO mainly acts on neutral and polar substrates, making substrate specificity the key distinction^[6]. For experimental applications, DAAO inhibitors increase D-serine exposure in rodents, while cross-species studies show weaker effects in monkeys and dogs, requiring careful model selection^[7]. Yeast-derived DAAO also enables chemogenetic H₂O₂ generation in defined subcellular sites, supporting redox pathway and oxidative-stress model design^[8].

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