Enzymes estrogens

There is some iiterature that examines fiavonoids such as apigenin as iigands for the estrogen beta receptor, and as an inhibitor of the enzyme estrogen synthetase (aromatase) (Kuiper et ai. 1998 Keiiis and Vickery 1984). These compounds do so potentiy, but the behaviorai significance of amounts observed in common preparations needs to be further investigated. 

Steroids are synthetic products of cholesterol [57-88-5]. The chemical stmcture of a steroid hormone is determined by sequential enzymatic processing of the cholesterol molecule. Steroid products differ among steroid-secreting glands because of differences in enzyme processing, eg, the production of estrogen by the ovary requires enzymatic steps that do not occur in the adrenal cortex. 

The alkynyl steroid (96) inactivates aromatase, an enzyme which catalyzes the conversion of androgen to estrogen. It has been suggested (81JA3221) that the inactivation process involves the oxidation of (96) to an oxirene which rearranges to an oxocarbene which then binds to the enzyme prosthetic group, thus inactivating it. 

CYP17 is the 17 alpha-hydroxylase and 17-20 lyase, two different reactions catalyzed by one enzyme and required for production of testosterone and estrogen, respectively. Defects in this enzyme affect development at puberty. 

Agarwal et al. 1978), the quantification of these specific enzymes may indicate that exposure to endosulfan has occurred. Blood tests, such as decay curves for aminopyrine in plasma, which are semiquantitative indices of liver enzyme induction, have been used successfully in the past to demonstrate enzyme induction in pesticide-exposed workers. Because numerous chemicals found at hazardous waste sites also induce these hepatic enzymes, these measurements are not specific for endosulfan exposure. However, measurements of enzyme activity, together with the detection of the parent compound or its metabolites in tissue or excreta, can be useful indicators of exposure. All of these potential biomarkers require further verification in epidemiological studies. Further studies with focus on the development of methods to separate and measure the estrogenicity of endosulfan in in vitro assays would be valuable since these assays are more sensitive and discriminative than other conventional biomarkers. Preliminary results have been presented by Sonnenschein et al. (1995). 

Simpson, E.R., Mahendroo, M.S., and Means, G.D. et al. (1994). Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocrine Reviews 15, 342-355. 

The estrogens are a family of hormones synthesized in a variety of tissues. 17P-Estradiol is the primary estrogen of ovarian origin. In some species, estrone, synthesized in numerous tissues, is more abundant. In pregnancy, relatively more estriol is produced, and this comes from the placenta. The general pathway and the subcellular localization of the enzymes involved in the early steps of estradiol synthesis are the same as those involved in androgen biosynthesis. Features unique to the ovary are illustrated in Figure 42-7. 

Estrogens are formed by the aromatization of androgens in a complex process that involves three hydroxyla-tion steps, each of which requires O2 and NADPH. The aromatase enzyme complex is thought to include a P450 monooxygenase. Estradiol is formed if the substrate of this enzyme complex is testosterone, whereas estrone results from the aromatization of androstenedione. 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

The adult male prostate contains abundant acid phosphatase which it secretes into the semen. The production of this enzyme is governed by the circulating levels of androgenic hormones. Castration or estrogen administration markedly reduces the prostatic urinary acid phosphatase of males. Other organs such as the liver, kidney, spleen, red cells and platelets also contain significant amounts of acid phosphatase. 

The enzyme aromatase catalyses the conversion of testosterone to estrogen. A number of in vitro studies have shown that phytoestrogens can inhibit aromatase (Adlercreutz et al, 1993 Kao et al, 1998 Pelissero et al, 1996). However, the high concentrations required to cause this effect in vitro are unlikely to be achieved in vivo following dietary exposure. 

Exemestane is an irreversible aromatase inactivator that binds to the aromatase enzyme to block the production of estrogen from androgens. Exemestane is absorbed rapidly after oral administration, with a terminal half-life of 24 hours. The drug is eliminated primarily by the liver and feces, with less than 1% of the dose excreted unchanged in the urine. Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women who have had disease progression following tamoxifen therapy. Side effects include hot flashes, fatigue, osteoporosis/bone fractures, and flulike symptoms. 

Enzymatic degradation was tested with commercial LAC from M. thermophila (2,000 U L ). E2 and EE2 were completely degraded even in the absence of mediators after 3 and 5 h, respectively, and after 1 h in the presence of some mediators. For El total removal was achieved in 8 h in the presence of VA and >70% for the other mediators after 24 h, whereas elimination reached 65% in the absence of mediators [8]. The immobilization of this enzyme by encapsulation in a sol-gel matrix [58] was employed for the treatment of a mixture of El, E2, and EE2 both in a batch stirred tank reactor (BSTR) operating in cycles and a continuous PBR. Removal of estrogens was >85% in the BSTR and 55%, 75%, and 60% for El, E2, and EE2, respectively, in the PBR. Both systems were able to reduce the estrogenic activity of the mixture in 63%. Likewise, the immobilization of VP in the form of CLEAs completely removed E2 and EE2 within 10 min from batch experiments, with a concomitant reduction of estrogenic activity, higher than 60% for both compounds [44]. 

The application of LAC for the removal of estrogens from municipal wastewater was assessed by Auriol and co-authors [59]. Different enzyme levels were tested and a LAC activity of 20,000 U L 1 was enough to achieve complete removal of El, E2, estriol (E3), and EE2 in 1 h from both the wastewater and the synthetic... 

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