Edelhoch H, Irace G, Johnson M L, Michot J L, Nunez J
J Biol Chem. 1979 Dec 10;254(23):11822-30.
The rates of oxidation of several goitrogens by lactoperoxidase and the rates of inactivation of lactoperoxidase by the same goitrogens have been measured. The influence of iodide on both reactions has also been evaluated. It has been shown by us that iodide acts catalytically in regulating lactoperoxidase activity at pH 8.8. The rate data have been analyzed by a computer program which solves the differential equations for the above mentioned reactions. From this computer analysis we have been able to obtain binding constants of the goitrogens and inactivation rate constants of lactoperoxidase. Iodide was shown to inhibit goitrogenic activity either by increasing the rate of drug oxidation or by reducing the rate of enzyme inactivation, or both, depending on the particular drug. Iodide had little or no effect on the goitrogen-binding constants. We have also shown that the relative rates of enzyme inactivation can be correlated with the potency of the goitrogen as an antithyroid drug.
已测定了几种致甲状腺肿物质被乳过氧化物酶氧化的速率以及相同致甲状腺肿物质使乳过氧化物酶失活的速率。还评估了碘化物对这两种反应的影响。我们已证明,在pH 8.8时,碘化物在调节乳过氧化物酶活性方面起催化作用。速率数据已通过一个计算机程序进行分析,该程序可求解上述反应的微分方程。通过这种计算机分析,我们能够获得致甲状腺肿物质的结合常数和乳过氧化物酶的失活速率常数。结果表明,碘化物抑制致甲状腺肿活性的方式,要么是提高药物氧化速率,要么是降低酶失活速率,或者二者兼具,这取决于具体的药物。碘化物对致甲状腺肿物质的结合常数几乎没有影响。我们还表明,酶失活的相对速率与致甲状腺肿物质作为抗甲状腺药物的效力相关。