Inhibitory effect of 6-azauracil on beta-alanine metabolism in rat.
The effect of 6-azauracil on beta-alanine metabolism was investigated in vivo in the rat. Both of the enzymes beta-alanine-oxoglutarate aminotransferase (aminobutyrate aminotransferase) and D-3-aminoisobutyrate-pyruvate aminotransferase [R)-3-amino-2-methylpropionate-pyruvate aminotransferase), which are beta-alanine catabolizing enzymes from rat liver and kidney, were inactivated by 6-azauracil injection, while dihydrouracil dehydrogenase, dihydropyrimidinase, and beta-ureidopropionase, which are pyrimidine metabolizing enzymes, were not affected. The content of beta-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. beta-Alanine-oxoglutarate aminotransferase and beta-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 beta-alanine in 6-azauracil-treated rat liver might be caused by the inhibition of beta-alanine catabolizing enzymes, but not by an increase in the uridine pool nor by the activation of pyrimidine metabolism.
Tamaki
N
N
Laboratory of Nutritional Chemistry, Faculty of Nutrition, Kobe-Gakuin University, Japan.
Fujimoto
S
S
Mizota
C
C
Kaneko
M
M
Kikugawa
M
M
D000409:Alanine / Q000378:metabolism*; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D050744:Dihydrouracil Dehydrogenase (NAD+); D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D011919:Rats, Inbred Strains; D014498:Uracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D014542:Uridine Monophosphate / Q000378:metabolism
D014498:Uracil; D014542:Uridine Monophosphate; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050744:Dihydrouracil Dehydrogenase (NAD+); D000581:Amidohydrolases; C021590:beta-ureidopropionase; C020047:dihydropyrimidinase; C100248:azauracil; D000409:Alanine