The in vivo decrease of beta-alanine-2-oxoglutarate aminotransferase activity caused by 6-azauracil and 5-fluorouracil.

methylhistidine), carnosine (ƒÀ-alanylhistidine) and CoA, and it is proposed to function in a limited number of synapses (1). It is well established that ƒÀ-alanine is a metabolite of uracil. Handschumacher (2) originally found that 6-azauridine 5'-phosphate is a competitive inhibitor of orotidine 5'-phosphate decarboxylase. Brody and Westheimer (3) purified orotidine 5'-phosphate decarboxylase from yeast using an affinity column of 5-(2-carboxyethyl)-6-azauridine 5'-phosphate carboxymethyl agarose. Moreover, the mode of action of 6-azauridine in its capacity as a growth inhibitor has been attributed to an inhibition of UTP biosynthesis by 6-azauridine 5'-phosphate (4) or incorporation of it into RNA (5). Recently, it has been proposed that 5-fluorouracil incorporated in RNA improves anti-tumor activity (6) and cytotoxicity (7). In previous paper (8), we purified ƒÀ-alanine-2-oxoglutarate amino transferase from rabbit liver and reported on its properties. In that study we found that 6-azauracil inhibited the activity of the enzyme. This report describes the decrease of ƒÀ-alanine-2-oxoglutarate aminotransferase caused by 6-azauracil and 5 -fl uorouracil with the concomitant increase of ƒÀ-alanine content in rat liver in vivo. Male Sprague-Dawley rats, weighing 100 to 120g, were housed in individual screen-bottom cages in a room maintained at 23•}1•Ž with 50% humidity and light regulation (12hr light per day). The animals were given commercial food pellets (CLEA Japan, Inc.) and water ad libitum. Three animals were used in each experimental subgroup. Ten mg each of 6-azauracil and 5-fluorouracil was dissolv ed in 0.4ml of 20% propylene glycol and subcutaneously injected into the rats. After the sacrifice of the rats, the liver and the whole brain were quickly removed