D-amino acid oxidase

DAAO in humans is a candidate susceptibility gene[2] and together with G72 may play a role in the glutamatergic mechanisms of schizophrenia.

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.

Currently, the link between human D-amino acid oxidase (hDAAO) activity and schizophrenia is being researched.

[4] 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.

[6] The consensus is that DAO is produced and is active in glial cells, most specifically in cerebellar type-1 and type-2 astrocytes,[1] and the D-serine amino acid that is produced by DAO in these cells has been shown to increase synaptic NMDA receptor activity.

[1] There is evidence to show that schizophrenia, as a neural phenomenon, is associated with both hyper- and hypoglutamatergic function, mediated by NMDA receptors.

Although, the G72 gene, which reportedly encodes the D-amino acid oxidase activator, may be involved in the development of schizophrenia.

[10] This is believed to be caused by plG72 binding limiting the amount of the enzyme that is catalytically competent, and can be negated by the cofactor or any active-site ligands.

The planar site’s chemical structure is formed by one or two fused rings and must have a negatively charged carboxylic group.

[5] D-amino acid oxidase is used in biotechnology primarily to produce antibiotics called cephalosporins.

This is important due to the effects of D-amino acids in the D-isomer or multiple enantiomers present in food has on the nutritional value.

RgDAAO is used in a process called gene-directed enzyme prodrug therapy (GDEPT) to treat tumors in cancer patients.

This treatment uses RgDAAO as the enzyme and D-alanine as a substrate to create a reactive oxygen species H2O2 as a product.

Changing the amount of D-amino acid oxidase transporters with the use of drugs has therapeutic effects on schizophrenia.

hDAAO head-to-head connection
SchizophreniaBrain