Goswami A, Rosenberg I N
Endocrinology. 1983 Apr;112(4):1180-7. doi: 10.1210/endo-112-4-1180.
The naturally occurring dithiol, dihydrolipoamide (DHL), has been found to be 6-10 times as potent as the synthetic dithiol, dithiothreitol, in stimulating iodothyronine outer ring monodeiodinase activity in the rat kidney. In the presence of NADH, the oxidized form is also active in stimulating the enzymatic activity in whole homogenates and in the postnuclear and mitochondrial, but not in the microsomal fraction. The covalently bound lipoamide in the mitochondrial alpha-keto acid dehydrogenase complexes, when reduced with substrates or NADH, was, however, ineffective. The activation of the enzyme by DHL was very similar to that obtained with dithiothreitol in respect to temperature dependence and inhibition by propylthiouracil and by dicoumarol, suggesting that these thiols activate the same enzyme through similar mechanisms. The higher potency of DHL cannot be explained on the basis of its greater lipophilicity or relatively proximal dithiol structure. The occurrence of DHL in mitochondria raises the possibility of a role as a thiol cofactor in enzymatic outer ring deiodination of T4 or rT3, although attempts to stimulate deiodination in mitochondrial preparations by reducing endogenous bound lipoamide were unsuccessful.
已发现天然存在的二硫醇二氢硫辛酰胺（DHL）在刺激大鼠肾脏中碘甲状腺原氨酸外环单脱碘酶活性方面，其效力是合成二硫醇二硫苏糖醇的6至10倍。在存在NADH的情况下，氧化形式在刺激全匀浆以及核后和线粒体部分的酶活性方面也具有活性，但在微粒体部分则无活性。然而，线粒体α-酮酸脱氢酶复合物中与共价结合的硫辛酰胺在用底物或NADH还原时却无作用。就温度依赖性以及丙硫氧嘧啶和双香豆素的抑制作用而言，DHL对该酶的激活作用与二硫苏糖醇所产生的激活作用非常相似，这表明这些硫醇通过相似的机制激活同一种酶。DHL效力更高的原因无法基于其更强的亲脂性或相对更接近的二硫醇结构来解释。线粒体中DHL的存在增加了其作为T4或rT3酶促外环脱碘作用中的硫醇辅助因子的可能性，尽管通过还原内源性结合的硫辛酰胺来刺激线粒体制剂中脱碘作用的尝试未获成功。
