β–GLUCURONIDASE AND THE ACTION OF STEROID HORMONES

β–GLUCURONIDASE AND THE ACTION OF STEROID HORMONES
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β-葡萄糖醛酸酶和类固醇激素的作用

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发表时间:
1951
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影响因子:
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通讯作者:
W. Fishman
W. Fishman
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文献类型:
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作者:
W. Fishman

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一开始就确定酶和类固醇激素领域的研究目标可能是可取的。首先,可以理解的是,性类固醇的生物学作用应该在酶现象的领域中寻求解释。因此,正如我们所知,生物体中的大多数生化反应是由特定的酶催化的这一概括被广泛接受和接受。此外,在确定各种维生素参与细胞必需的特定酶系统方面所取得的成功,反过来又使人们期望类固醇激素同样可以被证明是重要酶系统的组分。一般考虑。首先,将概述一些概念,这些概念可能适用于类固醇在组织酶系统中的参与。将仅参考图1和图2中所示的雌激素。图1是雌激素代谢的简化图,其指示体内雌激素的主要途径。可以看出,体内存在两种形式的雌激素,游离和结合。游离雌激素可能主要在胆汁中排泄,也可能在肝脏中被非特异性氧化酶氧化降解。雌激素结合物(其葡萄糖醛酸苷或硫酸盐)经尿液排泄。游离雌激素及其结合物都将刺激第二性器官的生长过程。因此,我们认为,雌激素作用的酶现象的解释应该在这些标记为A和B的机制中寻找,它们可能是同一个过程。雌激素作为酶系统的一个组成部分的利用最简单地表示在图2中。酶X,这是一个术语,意味着酶是假设的,尚未确定,应该是雌激素刺激组织生长的限制因素。如果我们可以从酶-维生素领域的经验中类推,迄今为止所研究的所有维生素辅酶在性质上都是酸性的。如果性类固醇被发现构成辅酶,那么这些激素将具有酸的功能,这样的预测可能不是太不合理。雌激素可能作为一种特异性底物参与酶系统,如图2所示。也许酶-底物复合物在生长中具有不同于其酶学意义的生理功能。在构成类固醇-酶现象这样一个新的和混乱的领域里,有必要区分由激素作用引起的初级和次级酶反应。在这方面,类固醇诱导生长的主要酶反应可以定义为类固醇作为辅酶、底物、激活剂或抑制剂直接参与的反应。因此,HOR的二级酶反应-
It may be desirable a t the outset to define the goals of research in the field of enzymes and the steroid hormones. In the first place, it is understandable that the explanation of the biological action of the sex steroids should be sought in the realm of enzymatic phenomena. Thus, as we know, the generalization that most biochemical reactions in the living organism are catalyzed by specific enzymes is widely held and accepted. Moreover, the success which has been realized in establishing the participation of various vitamins in essential specific enzyme systems of the cell has, in turn, led to the expectation that the steroid hormones may similarly be shown to be components of important enzyme systems. General Considerations. First, some of the concepts will be outlined which may apply to the participation of steroids in tissue enzyme systems. Reference will be made only to the estrogenic hormones presented in FIGURES 1 and 2. FIGURE 1 is a simplified picture of estrogen metabolism which indicates the main pathways of estrogen in the body. As can be seen, two forms of estrogen occur in the body, free and conjugated. The free estrogen may either be excreted mostly in the bile or be degraded oxidatively in the liver by non-specific oxidases. The conjugate of estrogen (either its glucuronide or sulfate) is excreted in the urine. Both free estrogen and its conjugates will stimulate growth processes in the secondary sex tissues. Accordingly, it is felt that the explanation of the action of the estrogens in terms of enzyme phenomena should be sought in these mechanisms labeled A and B, which may possibly be one and the same process. The utilization of estrogen as an integral component of an enzyme system is most simply represented in FIGURE 2. Enzyme X, which is the term signifying that the enzyme is hypothetical and as yet unidentified, should be the limiting factor in tissue growth stimulated by estrogen. If we may reason by analogy from experiences in the enzyme-vitamin field, all vitamin coenzymes which have been studied thus far are acidic in nature. It may not be too unreasonable to predict that, should the sex steroids be found to constitute coenzymes, these hormones will possess acid functions. Estrogen may participate in an enzyme system as a specific substrate, as in FIGURE 2. Perhaps the enzyme-substrate complex has a physiological function in growth which is distinct from its enzymological significance. It is necessary in a field as new and as confused as that constituting steroid-enzyme phenomena to distinguish between primary and secondary enzyme reactions resulting from hormonal action. A primary enzyme reaction of hormone-induced growth, in this regard, may be defined as one in which the steroid participates directly, either as coenzyme, substrate, activator, or inhibitor. Accordingly, secondary enzyme reactions of hor-