Amino acid levels in D-alanine-administered mutant mice lacking D-amino acid oxidase.

D-Alanine was administered orally to mutant mice lacking D-amino acid oxidase (EC 1.4.3.3). The mice had free access to drinking water containing 0.5% D- or L-alanine or 0.1% D-alanine for 2 weeks. The mice were then killed, and levels of the D- and L-enantiomers of free alanine, serine, proline, glutamate, and aspartate were determined in serum, liver, kidney, cerebrum, and cerebellum tissues. D-Alanine content increased by 60-fold (liver) to 110-fold (serum, brain), although the L-alanine level did not change. The increase of serum and brain D-alanine concentrations in animals fed 0.5% D-alanine was approximately five times more than that in animals fed 0.1% D-alanine, ie, the increase was roughly D-alanine dose-dependent in these tissues. The increase due to 0.5% D-alanine administration was reduced by 50% 17 hours after administration of D-alanine was stopped. Administration-induced increases in D-alanine levels in the cerebrum and cerebellum were not less than those in the serum, suggesting that D-alanine passed the blood-brain barrier quite freely. In the liver but not in other tissues, there were slight increases in D-serine and D-proline levels after administration of D-alanine. Administration of D-alanine produced no alterations in free glutamate and aspartate levels. No D-enantiomers of alanine, serine, proline, glutamate, or aspartate were detected in the liver and kidney tissue proteins of any animals, even in the mutant mice that received 0.5% D-alanine.