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The metabolism of 4-androstene-3,6,17-trione (AT), previously described as a suicide substrate for aromatase, and its irreversible binding to aromatase were studied by using human placental microsomes. AT was rapidly converted into 3 beta-reduced metabolite (3-OHAT) with an enzyme other than aromatase in the microsomes in the presence of NADPH under either aerobic or anaerobic conditions. The conversion was efficiently prevented by a steroid 5 alpha-reductase inhibitor. 3-OHAT was characterized as a competitive (Ki = 6.5 microM) and irreversible inhibitor of aromatase. Both 14C-labeled AT and 3-OHAT were demonstrated to be irreversibly bound to aromatase probably through a sulfur atom of the enzyme in time-dependent manners in the presence of NADPH, being accompanied with time-dependent losses of the enzyme activity. It was shown that the process of an apparent time-dependent loss of aromatase activity caused by AT even under conditions allowing its 3 beta-reduction should principally depend on the action of the parent inhibitor AT itself and not on that of the metabolite 3-OHAT. 相似文献
978.
979.
Masao Fujimoto Kazuo Uchida Morio Suzuki Hiroshi Yoshino 《Bioscience, biotechnology, and biochemistry》2013,77(6):605-610
Several guanineless mutants derived from Bacillus subtilis IAM 1145 were found to accumulate xanthosine in the culture broth. Further mutation of the guanineless mutants to adenine dependence led to remarkable increase in the accumulation of xanthosine. One of the guanine-adenine doubleless mutants, strain Gu-Ad-3-35, accumulated 8.9g of xanthosine per liter. Xanthosine was isolated in a crystalline form from the culture broth by a procedure involving charcoal treatment and ion-exchange chromatography. 相似文献
980.
A portion of the seed virus remained active even in the presence of excess antibody. With an early serum or relatively low concentrations of a hyperimmune serum, the presence of such unneutralizable virus was uncovered by the addition of complement. This unneutralizable persistent fraction (PF) was distinguished from sensitized virus surviving in insufficient antibody, because the latter was inactivated by a high concentration of antibody as quickly as the control virus. The level of the PF was constant regardless of the serum species, serum lot, dilution of serum, antibody class and complement requirement of antibody, being approximately 0.1% of the seed virus. Millipore filtration of the seed virus lowered this PF level to varying degrees depending upon the porosity. However, when filtered virus-serum mixtures were incubated at 37 C for a sufficient time and then filtered again, a portion of the unneutralized virus did pass a 0.22 μ membrane. Furthermore, virus sensitized with insufficient antibody showed no increase in resistance to complement after 10 hr incubation at 4 C. These results proved that viral aggregation was not the essential cause of the PF. It was confirmed, on the other hand, that the neutralization of virus by hyperimmune IgG followed a one-hit curve. Analysis of these data appeared to support Rappaport's postulation that the PF represented antibody-coated virus whose critical antigenic sites were all left unbound. 相似文献