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

Abstract

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.