Control of Ornithine Carbamoyltransferase Activity by Arginase in Bacillus subtilis

Partially purified Bacillus subtilis ornithine carbamoyltransferase is cooperatively inhibited by excess of ornithine. The inhibition is decreased by lowering of pH from 9.2 to 7.6 without altering the affinity of the enzyme for the neutral species of ornithine which seems to be its true substrate. Arginine and lysine partially reverse this inhibition without affecting the catalytic activity of the enzyme. 2‐Aminobutyrate, an inhibitor of the enzyme, competitive with respect to ornithine, is not able to replace ornithine in this excess‐substrate type of inhibition. Zn 2+ is also an inhibitor of ornithine carbamoyltransferase, with competitive action towards ornithine and its inhibition is added to the excess ornithine inhibition. These data suggest that ornithine carbamoyltransferase has a regulatory site for ornithine, distinct from the catalytic one. Partially purified arginase, prepared from the same strain, increases the inhibition of ornithine carbamoyltransferase by excess of ornithine when arginine is present. An association of the two enzymes is suggested by molecular sieving. These data postulate that ornithine carbamoyltransferase is regulated by arginase under the control of arginine and ornithine. The other substrate, carbamoyl phosphate, is not involved in this regulatory mechanism. Lysine and Zn 2+ inhibit arginase competitively with respect to arginine without altering the effect of this enzyme on the inhibition of ornithine carbamoyltransferase. 2‐Aminobutyrate inhibits arginase non‐competitively with respect to arginine and prevents the inhibition of arginase towards ornithine carbamoyltransferase. These results suggest that arginase possesses a regulatory site for arginine, distinct from the catalytic one, which is also involved in the control mechanism.