Inhibitory effect of 6-azauracil on .BETA.-alanine metabolism in rat.

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The effect of 6-azauracil on j3-alanine metabolism was investigated in vivo in the rat. Both of the enzymes β-alanine-oxoglutarate aminotransferase (aminobutyrate aminotransferase) and D-3-aminoisobutyrate-pyruvate aminotransferase ((R)-3-amino-2-methylpropionate-pyruvate aminotransferase), which are β-alanine catabolizing enzymes from rat liver and kidney, were inactivated by 6-azauracil injection, while dihydrouracil dehydrogenase, dihydropyrimidinase, and J3-ureidopropionase, which are pyrimidine metabolizing enzymes, were not affected. The content of β-alanine was increased, but the level of uridine and uracil in rat liver was not affected, by 6-azauracil. When a crude enzyme preparation was passed through a Sephacryl S-200 column, both enzymes could be separated from each other. β-Aaanine-oxoglutarate aminotransferase and β-alanine-pyruvate aminotransferase activities in rat liver decreased to 27.4% and 63.9%, respectively, upon 6-azauracil injection, and those in kidney were 11.7% and 38.3%, respectively. From these findings, it is suggested that the accumulation of β-alanine in 6-azauracil-treated rat liver might be caused by the inhibition of β-alanine catabolizing enzymes, but not by an increase in the uridine pool nor by the activation of pyrimidine metabolism.
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