D-amino acid oxidase

D-amino acid oxidase (DAAO; also OXDA, DAMOX) is an enzyme with the function on a molecular level to oxidize D-amino acids to the corresponding imino acids, producing ammonia and hydrogen peroxide. This results in a number of physiological effects in various systems, most notably the brain. The enzyme is most active toward neutral D-amino acids, and not active toward acidic D-amino acids. One of its most important targets in mammals is D-Serine in the central nervous system. By targeting this and other D-amino acids in vertebrates, DAAO is important in detoxification. The role in microorganisms is slightly different, breaking down D-amino acids to generate energy. D-amino acid oxidase (DAAO; also OXDA, DAMOX) is an enzyme with the function on a molecular level to oxidize D-amino acids to the corresponding imino acids, producing ammonia and hydrogen peroxide. This results in a number of physiological effects in various systems, most notably the brain. The enzyme is most active toward neutral D-amino acids, and not active toward acidic D-amino acids. One of its most important targets in mammals is D-Serine in the central nervous system. By targeting this and other D-amino acids in vertebrates, DAAO is important in detoxification. The role in microorganisms is slightly different, breaking down D-amino acids to generate energy. DAAO is expressed in a wide range of species from yeasts to human. It is not present in plants or in bacteria which instead use D-amino acid dehydrogenase. DAAO in humans is a candidate susceptibility gene and together with G72 may play a role in the glutamatergic mechanisms of schizophrenia. DAAO also plays a role in both biotechnological and medical advancements. Risperidone and sodium benzoate are inhibitors of DAAO. D-amino acid oxidase should not be confused with diamine oxidase as they are both sometimes referred to as DAO. In 1935, Hans Adolf Krebs discovered D-amino acid oxidase after an experiment with porcine kidney homogenates and amino acids. Shortly after, Warburg and Christian observed the oxidase had a FAD cofactor making it the second flavoenzyme to be discovered. In the upcoming years other scientists developed and improved the purification procedure for a porcine D-amino acid oxidase. In 1983, inhibitors for the oxidase were discovered. In 2006, the 3D structure of the oxidase was published. Currently, the link between human D-amino acid oxidase (hDAAO) activity and schizophrenia is being researched. While D-amino acid oxidase differs to some extent between various organisms, the structure is basically the same across most eukaryotes, excluding plants. This enzyme is a flavoprotein belonging to the FAD dependent oxidoreductase family, and acts on the CH-NH2 group of D-amino acid donors with oxygen as acceptor. It is also considered a peroxisomal enzyme containing FAD as a cofactor. Each DAO monomer has an FAD-binding domain (FBD) containing a Rossman fold, and a substrate-binding domain (SBD) that also forms an interface with the other monomer in the protein. DAO exists as a dimer, with each monomer containing both an FBD and SBD. Each monomer is composed of 347 amino acids in human DAO, though among other eukaryotes the protein can range from 345 to 368 amino acids long. In human DAO, the two monomers are connected in a head-to-head fashion. DAO of other organisms, such as yeast, can be present as head-to-tail dimers. The hDAAO gene is found on chromosome 12 and contains 11 exons. DAO is capable of reducing oxygen quickly, and when reduced can stabilize anionic red semiquinone, and it is capable of forming a covalent bond with sulfites. These are all typical properties associated with flavoproteins. Human DAAO has slightly different properties from other DAAO molecules, including a weaker ability to bind FAD and decreased rate of reaction for some molecules, such as flavin. DAO acts in the brain to oxidize specific D-amino acids using the FAD region (flavin adenine dinucleotide region) and is commonly thought to be produced in the hindbrain, although there is new evidence of DAO expression in the forebrain as well. The DAO present in the forebrain seems to be inactive, however, causing speculation on the topic of DAO function in the forebrain as opposed to the hindbrain where the function is more well-known. The consensus is that DAO is produced and is active in glial cells, most specifically in cerebellar type-1 and type-2 astrocytes, and the D-serine amino acid that is produced by DAO in these cells has been shown to increase synaptic NMDA receptor activity. There is evidence to show that schizophrenia, as a neural phenomenon, is caused by the inappropriate activity of NMDA receptors and the related increase in glutamate activity associated with NMDA receptors.