Studies of D-amino acid oxidase.

The significance of mammalian D-amino acid oxidase (DAAO) has not been established. Little is known of the source of its substrates, since only the L form appears to be involved in the me tabolism of amino acids in higher animals. In vivo isotope dilution studies (22) have indicated that normal mammals contain no free D-tyrosine or D-glutamic acid, although Kögl (13) has re peatedly reported the presence of D-glutamic acid in tumors. The latter finding has been chal lenged by several investigators (18, 22) but recently has received independent support (11). D-amino acids have been shown to occur in bacteria, molds, and, possibly, viruses. It appears possible that D-amino acids from intestinal flora are absorbed from the gut and serve as the sub strate. The considerable enzymatic capacity of the DAAO in the liver and kidney, which are the enzyme's principal sites, would be expected to prevent the accumulation of D-amino acids in the plasma and might explain the failure of isotope dilution experiments to detect D-amino acids in the rat. The rapid removal of D-amino acids from the plasma by DAAO and by excretion in the urine (1, 6, 7, 10, 17, 24) has complicated studies on possible incorporation of the unnatural isomers into proteins or other compounds. The present study was concerned with the development of in vitro and in vivo assays of DAAO and studies on the relation of intestinal flora, D-amino acid feeding, and tumor growth to the amount of enzyme found in mouse kidney. The distribution and metabolism of o-alanine in nephrectomized normal and tumor-bearing mice were also studied.