Regulation of Escherichia coli ornithine transcarbamylase by orotate

Ornithine transcarbamylase from Escherichia coli, strain W, exhibits negative cooperativity with respect to ornithine, and the enzymatic activity is further regulated by orotate. The effect of orotate on ornithine transcarbamylase is dependent not only upon the carbamylphosphate concentration, but also upon the concentration of ornithine. At high concentrations of carbamylphosphate (10 mM), a conversion from negative cooperativity to positive cooperativity is observed with 10 mM orotate. At 1 mM carbamylphosphate, however, 10 mM orotate activates the enzyme at low ornithine concentrations, but as the ornithine concentration is increased above 5 mM, inhibition is observed. Thus, a regulatory link has been established between the pathways of arginine biosynthesis and pyrimidine biosynthesis, each of which utilizes carbamylphosphate.