Rinderknecht H, Friedman R M
Biochim Biophys Acta. 1976 Dec 8;452(2):497-502. doi: 10.1016/0005-2744(76)90200-x.
Rare earths were found to be powerful inhibitors of enteropeptidase-catalyzed (enterokinase, EC 3.4.21.9) activation of trypsinogen. Inhibition was complete at a La3+ concentration of 12.5-10(-6) M in the assay system used and still detectable at a concentration of 1.25-10(-6) M. Inhibition was observed with all lanthanides tested. No significant differences between individual metals could be established under the conditions of the inhibition assay. Increasing ionic strength decreased enzyme activity and progressively diminished the inhibitory effect of rare earth ions suggesting an electrostatic basis for the mechanism of this inhibition. La3+ did not significantly affect enteropeptidase-mediated hydrolysis of N-benzoyl-L-arginine ethyl ester. Its inhibitory effect on activation of trypsinogen by enteropeptidase, therefore, must be attributed to interaction with the zymogen rather than the enzyme. Kinetic measurements show that inhibition by rare earths is noncompetitive in nature. Binding of lanthanides to the tetraaspartyl sequence near the aminoterminus of trypsinogen may prevent this group from interacting with a critical specificity subsite on the enzyme.
已发现稀土元素是肠肽酶催化（肠激酶，EC 3.4.21.9）胰蛋白酶原激活的强效抑制剂。在所使用的测定系统中，当La³⁺浓度为12.5×10⁻⁶ M时抑制作用完全，在1.25×10⁻⁶ M浓度时仍可检测到。在所测试的所有镧系元素中均观察到抑制作用。在抑制测定条件下，无法确定各金属之间的显著差异。增加离子强度会降低酶活性，并逐渐减弱稀土离子的抑制作用，这表明这种抑制机制有静电基础。La³⁺对肠肽酶介导的N-苯甲酰-L-精氨酸乙酯水解没有显著影响。因此，其对肠肽酶激活胰蛋白酶原的抑制作用必定归因于与酶原而非酶的相互作用。动力学测量表明，稀土元素的抑制本质上是非竞争性的。镧系元素与胰蛋白酶原氨基末端附近的四天门冬氨酸序列结合可能会阻止该基团与酶上的关键特异性亚位点相互作用。
