Chorismate mutase-prephenate dehydrogenase from Escherichia coli: cooperative effects and inhibition by L-tyrosine.
The effects of a variety of structural analogs of L-tyrosine on the mutase and dehydrogenase activities of hydroxyphenylpyruvate synthase have been investigated. From these studies it is concluded that the alpha-NH3+ alpha-COO-, and the 4-OH groups are essential for binding of L-tyrosine as an inhibitor of the dehydrogenase and that the L configuration is also essential. Dixon plots for inhibition of the dehydrogenase activity by some of these analogs were nonlinear and could be described by a velocity equation that is the ratio of quadratic polynomials (a 2/1 function). Dixon plots for inhibition of the mutase by prephenate at low concentrations of chorismate could also be described by a 2/1 function, but at low concentrations of prephenate chorismate acts as an apparent hyperbolic activator of the dehydrogenase activity. Up to concentrations of 300 microM, L-tyrosine activates the mutase but acts as a potent inhibitor of the dehydrogenase. Such data for the dehydrogenase could not be described by a 2/1 function in 1/[prephenate] but could be fitted to the Hill equation with increasing concentrations of L-tyrosine in the presence of 1.0 mM NAD yielding increasing values for the Hill number (n): in the absence of L-tyrosine, n = 1.6 +/- 0.1; at 150 microM L-tyrosine, n = 2.1 +/- 0.1; at 300 microM L-tyrosine, n = 2.3 +/- 0.4. L-Tyrosine bears a close structural resemblance to both prephenate and hydroxyphenylpyruvate, and evidence is presented which is consistent with L-tyrosine acting as a competitive inhibitor with respect to prephenate of the dehydrogenase.
D000218:Adamantane / Q000494:pharmacology; D002827:Chorismic Acid / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D008433:Mathematics; D009243:NAD / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D011303:Prephenate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014443:Tyrosine / Q000494:pharmacology*
D009243:NAD; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D010088:Oxidoreductases; D011303:Prephenate Dehydrogenase; D002827:Chorismic Acid; D000218:Adamantane