Abstract
Summary
Inhibition of nucleic acid metabolism by 2-thiouracil was investigated using Escherichia coli and an auxotroph which required uracil or orotic acid for growth. Linear increases of 2-thiouracil concentration in minimal salt medium produced logarithmic decreases in the growth rate of Escherichia coli. Uracil reversed the inhibition, and neither growth rate nor growth density was reduced by high concentrations of 2-thiouracil in the presence of the minimum amount of uracil required for growth of the uracil-requiring Escherichia coli. 2-Thiouracil did not inhibit the utilization of uracil and produced only partial inhibition (25%) of the utilization of orotic acid.
Dihydro-L-orotic acid, DL-ureidosuccinic acid, and L-aspartic acid were tested for ability to reverse 2-thiouracil inhibition. Only DL-ureidosuccinic acid clearly reversed this inhibition. An increase in 2-thiouracil concentration did not decrease the ability of DL-ureidosuccinic acid to reverse growth inhibition, indicating that 2-thiouracil does not inhibit L-ureidosuccinic acid utilization, but inhibits its formation or the formation of precursors. L-ureidosuccinic acid precursors are necessary for protein synthesis: thus aspartate transcarbamylase which catalyzes the formation of L-ureidosuccinic acid is considered to be the specific site of inhibition.
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