Biological role of D-amino acid oxidase and D-aspartate oxidase. Effects of D-amino acids.

Abstract

D-Amino acids administered to animals are absorbed by the intestine and transported through the blood-stream to solid tissues where they are oxidized in vivo by D-amino acid oxidase and D-aspartate oxidase to produce the same compounds they do in vitro; i.e. NH3, H2O2, and the keto acid corresponding to the amino acid ingested. In the liver and kidneys of the animals, an inverse relationship exists between the occurrence of D-amino acids and these oxidative enzymes. For example, younger animals have lower amounts of these oxidases and consequently higher concentrations of free D-amino acids compared to adult animals. If the ingested D-amino acids are not metabolized by these enzymes, they will accumulate in the tissues and may provoke serious damage, e.g. suppression of the synthesis of other essential enzymes and inhibition of the growth rate of the animals. A specific enzyme induction for these D-amino acid oxidases exists in young rats following ingestion of free D-amino acids by the mother. Specifically, when a mother rat ingests D-Ala or D-Asp during pregnancy and suckling, an increase in D-amino acid oxidase or D-aspartate oxidase is observed in the liver and kidneys of the baby rats. These results suggest that the in vivo biological role of these oxidases in animals is to act as detoxifying agents to metabolize D-amino acids which may have accumulated during aging.