Abstract

Aspartate transcarbamylase was partially purified from rat liver, Morris hepatoma 5123-A or D, Hepatoma 7800, and Novikoff hepatoma and was shown to be inhibited by pyrimidine deoxyribonucleosides and deoxyribonucleotides. The pyrimidine analogs, 5-bromo-2'-deoxyuridine, 5-bromouridine, 5-bromo-2'-deoxycytidine, 5-fluoro-2'-deoxyuridine, 5-fluorouridine, 5-fluoro-2'-deoxycytidine, 5-iodo-2'-deoxyuridine, also inhibited enzymatic activity. The enzyme, however, was most effectively inhibited by 2'-deoxyadenosine-5'-monophosphate (or 2'-deoxyguanosine-5'-monophosphate d-DMP) and by 2'-deoxyadenosine or 2'-deoxyguanosine. Aspartate transcarbamylase was shown to be identical in liver and in the hepatomas by pH optimum, K m values for carbamyl phosphate and aspartate, V max , degree of inhibition by Cu ++ , by the pyrimidines, and by the inhibition constants for BCDR, FUDR, thymidine, and d-AMP (or d-GMP). It was concluded that negative feedback inhibition of pyrimidine biosynthesis occurs in hepatomas as well as in liver, and to the same extent. Furthermore, the control of aspartate transcarbamylase by d-AMP (or d-GMP) may play a significant role in vivo . * This investigation was supported by an American Cancer Society Institutional Research grant and by a grant from the Anna Fuller Fund.