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1.
Synthesis of 2,4-bis(bromomethyl)estradiol-17 beta 3-methyl ether (BBE2M) was accomplished by reducing a methanolic solution of 2,4-bis(bromomethyl)estrone methyl ether with sodium borohydride. In 0.5 M phosphate buffer, pH 7.0, 25 degrees, BBE2M readily reacts with Ellman's anion and alkylates cysteine to form a steroid-amino acid conjugate. Stoichiometry of the reaction indicates that the bromosteroid is divalent with cysteine. Tryptophan and histidine react more slowly with the bromosteroid. Estrogenic activity of BBE2M was evaluated in ovariectomized rats by uterine intraluminal administration and quantitation of glucose-6-phosphate dehydrogenase (D-glucose-6-P:NADP+ oxidoreductase, EC 1.1.1.49) activity in the uterus. BBE2M induced glucose-6-phosphate dehydrogenase activity as did estradiol-17 beta or estradiol-17 beta 3-methyl ether (E2M). BBE2M was more persistent in activity than E2M. Histological examination of uterus following BBE2M treatment shows classic estrogenic morphology. BBE2M covalently binds to the cytoplasmic estrogen receptor of calf uterus. Such binding is prevented by pretreatment of the receptor protein with estradiol-17 beta. The covalently bound steroid-receptor complex appears to stimulate RNA synthesis in isolated nuclei from calf endometrium. 相似文献
2.
The 9β isomers of estradiol-17β, estradiol-17α, estrone and 17-ethinylestradiol-17β were synthesized and compared with their 9α-counterparts in the rat uterine cytosol estrogen receptor, utero-tropic, and gonadotropin release inhibition assays. Except for 17-ethinyl-9β-estradiol-17β which was as active as its 9α isomer in the uterotropic assay, none of the 9β estrogens exhibited any biological activity which was equal to or greater than their 9α counterparts. For examples, 9β-estradiol-17β was as active as estradiol-17β, and 9β-estrone was as active as estrone in the uterotropic assay. 相似文献
3.
The metabolism of estradiol-17β by the guinea pig uterus late in pregnancy was studied and .Whole uteri were examined for estrogen metabolites one hour following an intravenous injection of [3H]-estradiol-17β or uterine sections were examined after incubation for one hour at 37°C in medium containing [3H]-estradiol-17β.In both instances uterine tissue metabolized estradiol-17g to five products: estrone, estrone-3-sulfate, 17β-estradiol-3-sulfate, estrone-3-glucuronide and 17β-estradiol-3-glucuronide. Of the total radioactive products 11 – 43% were glucuronides, 17 – 26% were sulfates and 4 – 17% was estrone. These results indicate that the guinea pig uterus actively transforms estradiol-17β into glucuronides and sulfates late in pregnancy. 相似文献
4.
The structure activity relationship of nine compounds were studied and compared to lidocaine. The extent of local anesthetic activity was ascertained by the tail pinch method in mice, and by the isolated frog sciatic nerve method. The effective and lethal dose in 50% of the animals was also determined. Three of the nine compounds appeared to possess significant local anesthetic activity in the studies and thus were selected for further investigation . The studies also indicated that two of the three were more toxic than lidocaine. The results demonstrated that methyl substitution at positions 2,3 and 5 on the benzene ring produced a compound of slightly more anesthetic potency in an acid medium. At pH 7.8 all three compounds approached the potency of lidocaine. These data indicate that methyl substitution at other than the ortho position of the benzene ring generally results in compounds of lesser local anesthetic activity while tending to increase the toxicity. 相似文献
5.
Two high affinity estrogen binding proteins of different specificity in the immature rat uterus cytosol 总被引:6,自引:0,他引:6
The presence of two high affinity estrogen binding proteins in the uterine cytosol of the immature rat has been observed.Besides the 8 S cytosol estrogen , there is a 4–5 S fraction binding estradiol and estrone with a large capacity. In fact, the two binding systems have a different affinity for estradiol and estrone, the receptor binding more the former and the 4–5 S fraction more the latter. Exposure of the cytosol to specific anti-α1-Fetoprotein antibodies suppresses a large part of the 4–5 S binder, if not the totality. Moreover the estrogen binding 4–5 S fraction decreases with increasing age until puberty, while the increases. These results suggest therefore that the estradiol-estrone binding 4–5 S peak of the uterine cytosol is mainly made up of Estradiol Binding Plasma Protein-α1-Fetoprotein (EBP-AFP). Also they confirm that “cytosol” should be taken as an operational fraction which may include extracellular components.During the course of these experiments, it has been observed that the increase of the estradiol is more rapid than the other uterine cytosol proteins until the 8th day, and that there is a second period of growth when it follows the development of the uterus and of the animal, as if it had reached a constant number of binding sites per cell. 相似文献
6.
A method for demonstrating proestrogens has been developed. The method involves the incubation of the potential proestrogen with liver microsomes and NADPH in the presence of rat uteri, followed by examination of the effects of metabolism of the compound on the distribution of uterine estrogen receptor (R) in the cytosol (Rc) and in the nucleus (Rn). Thus, we examined whether DDT derivatives, which possess estrogenic activity , exhibit pro-estrogenic properties . Using this method, it appears that methoxychlor is a proestrogen, since the presence of microsomal enzymatic activity is required for methoxychlor to elicit translocation of uterine Rc into the nucleus, namely, the lowering of Rc and elevation of Rn. By contrast, o,p'DDT was active in translocating Rc and did not require the presence of microsomal enzymes for activity. 相似文献
7.
A betaine:homocysteine methyltransferase activity was demonstrated in the cell-free extracts from the fungus . Among methionine-requiring mutants which do not grow on homocysteine one class responds to betaine indicating that this compound can serve as a methyl donor in methionine synthesis . Mutants of the second class which grow only on methionine were shown to have betaine: homocysteine — and methyltetrahydrofolate: homocysteine methyltransferases simultaneously impaired. 相似文献
8.
Clinical and field reports have suggested that phosphorus is a major factor affecting the reproductive performance of dairy cattle. Seven milking cows were fed commercial meal with different ratio. Chemical analysis were carried out on the uterine fluids and the blood serum collected at four stages of the estrous cycle.Sodium, potassium and magnesium levels did not show any variation between the groups. Calcium concentrations were lower in the serum of the phosphorus treated cows and the uterine secretions showed significant variations. Phosphorus levels were also affected in the blood serum but no statistical difference was observed. The presumed improvement of reproductive performance in the field should be associated with some indirect effect rather than with a modification of uterine environment. 相似文献
9.
Robert H. White 《Biochemical and biophysical research communications》1983,112(1):66-72
A method has been devised for measuring the abundance of sulfur-34 in the hydrogen sulfide released upon the acidification of cells. Evidence is presented, based on the rate at which the hydrogen sulfide is released from the cells as well as the total amount released, that this hydrogen sulfide originates from the iron-sulfur proteins present in the cells. The sulfur-34 abundance in this hydrogen sulfide which was isolated from cells grown with [sulfane-34S]thiocystine, a compound which can differentially label the sulfur-34 abundance of cysteine and hydrogen sulfide, shows cysteine sulfur and not hydrogen sulfide to be the origin of the sulfide sulfur of iron-sulfur proteins in aerobically grown 相似文献
10.
The 2′,3′-dialdehyde of ADP, obtained by periodate oxidation of ADP, inhibited the hydrolytic activity of the purified Ca2+, Mg2+-activated ATPase of . In the initial stages of the reaction inhibition was due to the reaction of 1 mol inhibitor/active site. When non-specific labelling of amino groups by the dialdehyde was lowered by the simultaneous presence of 15 mM ATP in the reaction mixture, 3 mol “ATP-protectable” binding sites/mol ATPase were found. “ATP-protectable” binding of the dialdehyde was not observed when the hydrolytically inactive ATPase of an mutant of was used although binding of the inhibitor to non-protected amino groups still occurred. This suggests that the mutant ATPase is unable to bind ATP or that the amino groups with which the dialdehyde reacts in the native enzyme are absent or masked. 相似文献
11.
C. H. Spilman K. K. Bergstrom D. C. Beuving 《Prostaglandins & other lipid mediators》1980,20(6):1061-1074
Serum progesterone and uterine levels of diamine oxidase (DAO) activity were determined during pregnancy in hamsters. Progesterone was elevated on Day 1 of pregnancy, had a transient peak on Day 5, remained relatively constant on Days 6–10, and then increased on Days 13 and 14. Uterine DAO activity could not be detected until Day 7 of pregnancy, approximately 1 days after the initiation of implantation. DAO activity was associated with placental tissue, and more than 90% of the activity was localized in the maternal placenta. The temporal relationship between changes in serum concentrations of progesterone and uterine levels of DAO activity following PG administration also was studied. Serum progesterone was significantly depressed by 6 hr after treatment with PGs on Day 7 of pregnancy. However, uterine levels of DAO activity at 6 hr in the treated animals were not different from those in control animals. In contrast, both the serum progesterone concentrations and uterine levels of DAO activity were significantly lower at 24 hr after PG treatment. The effects of PG treatment on uterine DAO activity were completely blocked by concomitant administration of progesterone. However, concomitant administration of Provera® only blocked the effect of one PG analog that was tested (9-deoxo-9-methylene-16,16-dimethyl0-PGE2). The data indicate that changes in uterine DAO activity following treatment with the PGs used here are primarily a consequence of a decrease in peripheral progesterone (i.e. a luteolytic effect of the PG). 相似文献
12.
C.R. Pace-Asciak M.C. Carrara Z. Domazet 《Biochemical and biophysical research communications》1977,78(1):115-121
Two main urinary metabolites of 6K-PGF1α were isolated after intravenous injection of this compound into adult male Wistar rats. The structures were identified as: dinor 6K-PGF1α and dinor ω-1-hydroxy 6K-PGF1α. The structures of these two novel products were identified by gas chromatographymass spectrometry of the methyl and ethyl ester derivatives of the O-methyl-oxime trimethylsilyl derivatives and the methyl ester O-methyloxime t-Butyl-dimethylsilyl ether derivatives. These results indicate that the main pathway of metabolism of 6K-PGF1α is via β-and ω-oxidation and not via the prostaglandin 15-hydroxydehydrogenase pathway in this species. 相似文献
13.
T Yagi H Kagamiyama M Nozaki 《Biochemical and biophysical research communications》1979,90(2):447-452
Aspartate aminotransferases from pig heart cytosol and mitochondria, B and accepted L-cysteine sulfinate as a good substrate. The mitochondrial isoenzyme and the enzyme showed higher activity toward L-cysteine sulfinate than toward the natural substrates, L-glutamate and L-aspartate. The cytosolic isoenzyme catalyzed the L-cysteine sulfinate transamination at 50% the rate of L-glutamate transamination. The enzyme had the same reactivity toward the three substrates. Antisera against the two isoenzymes and the enzyme inactivated almost completely cysteine sulfinate transamination activity in the crude extracts of pig heart muscle and B, respectively. These results indicate that cysteine sulfinate transamination is catalyzed by aspartate aminotransferase in these cells. 相似文献
14.
K Okazaki 《Biochemical and biophysical research communications》1975,64(1):20-27
Thiamine pyrophosphokinase (E.C. 2.7.6.2.) from was found to require the presence of a non-protein, non-metal compound for its activity. -Inositol was found capable of stimulating the kinase activity in the presumably resolved but otherwise crude sample of the enzyme. The hexytol was also found capable of inducing the enzyme in growing yeast cells. The cultured yeast cells, in which the kinase had been induced, were used as source of the enzyme for its purification. The compound that had been left adsorbed to the final column of DEAE-Sephadex was proved to have a coenzyme activity towards the enzyme and tentatively identified with -inositol 1-pyrophosphate. A sample of synthetic -inositol 1-pyrophosphate was made and its coenzyme activity was observed. 相似文献
15.
Kuo-Chang Tang Anthony E. Pegg James K. Coward 《Biochemical and biophysical research communications》1980,96(3):1371-1377
The title compound (), was designed and synthesized based on mechanistic data concerning enzyme-catalyzed alkyl transfer reactions, applied in this case to aminopropyl transferases. The inhibition by of one such enzyme, spermidine synthase, was both potent (I50 = 4 × 10?7M) and specific. A closely related aminopropyltransferase, spermine synthase was only minimally affected by high concentrations of . Similar, although not as marked, specifity between the two aminopropyltransferases was observed with the corresponding methyl sulfonium salt, . Studies with structurally related compounds support the hypothesis that the strong inhibition of spermidine synthase by derives from the incorporation in this compound of important features of the transition-state structure of this enzyme-catalyzed reaction. 相似文献
16.
The effects of 19-hydroxy-prostaglandins (19-OH-PGs) were tested on the rabbit oviduct and uterus and on the rhesus monkey () uterus. The 19-OH-PGEs suppressed spontaneous oviductal and uterine activity in the rabbit. The qualitative effect on the rabbit oviduct of 19-OH-PGEs was similar to that of PGE2. However, the typical response of the rabbit uterus to PGE2 was an increase in muscle activity. With regard to the rabbit oviduct, 19(R)-OH-PGE2 was as potent as PGE2, but 19(S)-OH-PGE2 was approximately as potent as PGE2. Based on the dose of 19-OH-PGEs usually required to cause a minimal suppression and the dose of PGE2 required to cause a minimal stimulation of rabbit uterine activity, 19(R)-OH-PGE2 was twice as potent as PGE2 while 19(S)-OH-PGE2 was as potent as PGE2. Stimulatory effects on the rabbit oviduct and uterus were observed following administration of 19-OH-PGEs and PGF2α. The potency on the rabbit oviduct of 19(S)-OH-PGF2α was about to that of PGF2α; the potency of 19(R)-OH-PGF2α was about to that of PGF2α. Both 19-OH-PGFs were approximately to as potent as PGF2α on the rabbit uterus. At the doses tested 19-OH-PGFs were inactive on the monkey uterus. Thus, these compounds are at least as active as PGF2α. In contrast, 19(R)-OH-PGE2 had approximately the same potency as PGE2 in stimulating monkey uterine activity; but 19(S)-OH-PGE2 was approximately as potent as PGE2. 相似文献
17.
Kunisuke Nagamatsu Yasumasa Kido Tadao Terao Takashi Ishida Satoshi Toki 《Life sciences》1982,30(13):1121-1127
The ability of sulfhydryl compounds to provide protection against the acute toxicity of morphinone was investigated in mice. Subcutaneous administration of morphinone produced a reduction of hepatic non-protein sulfhydryl concentration. Pretreatments of mice with glutathione or cysteine significantly increased the survival rate of mice given a lethal dose of morphinone, whereas morphinone lethality was markedly potentiated by diethyl maleate. On the other hand, the administration of morphine produced a dose dependent reduction of hepatic non-protein sulfhydryl contents. However, neither glutathione nor cysteine protected mice from the acute toxicity of morphine. A possible explanation for these observations was proposed as follows: morphine is oxidized by morphine 6-dehydrogenase to morphinone, and the morphinone thus produced decreases the sulfhydryl contents in the liver. This mechanism is supported by the fact that morphinone reacts easily with glutathione and cysteine . 相似文献
18.
B F Coles J R Smith R C Garner 《Biochemical and biophysical research communications》1977,76(3):888-892
Racemic 3a,8a-dihydrofuro[2,3-b]benzofuran has been chemically synthesized as a model of the vinyl ether structure of aflatoxin B1 (AFB1) and tested for mutagenicity. In the presence of 9000g rat liver supernatant fraction the compound induced his+ revertant colonies in TA 100 but with only one five-thousandth the activity of AFB1. No mutagenicity was found when strain TA98 was used. Omission of the rat liver preparation abolished mutagenic activity. The reduced compound, tetrahydrofurobenzofuran, was inactive as a mutagen either in the presence or absence of the rat liver supernatant. 相似文献
19.
Klaus Gietzen Peter Adamczyk-Engelmann Andreas Wüthrich Anka Konstantinova Hermann Bader 《生物化学与生物物理学报:生物膜》1983,736(1):109-118
Compound , a condensation product of N-methyl-p-methoxyphenethylamine with formaldehyde, is composed of a family of cationic amphiphiles differing in the degree of polymerization. Compound was found to be a potent inhibitor of the calmodulin-activated fraction of brain phosphodiesterase and red blood cell Ca2+-transport ATPase, with IC50 values of 0.3 and 0.85 μg/ml, respectively. However, the basal activity of both enzymes is not at all suppressed by the drug at concentrations up to 300 μg/ml. Inhibition of Ca2+ transport into inside-out red blood cell vesicles by compound follows a similar pattern in that basal, calmodulin-independent, transport is also not affected by the drug. Kinetic analysis revealed that the stimulation of Ca2+-transport ATPase induced by calmodulin is inhibited by compound according to a competitive mechanism. It was demonstrated that the inhibitory constituents of compound bind to calmodulin in a Ca2+-dependent fashion. Comparison of the specificity of several anti-calmodulin drugs showed that compound is the most specific inhibitor of the calmodulin-dependent fraction of red blood cell Ca2+-transport ATPase that has been described hitherto. In addition, compound was found to be a rather specific inhibitor of the calmodulin-induced activation of Ca2+-transport ATPase when compared with the stimulation induced by an anionic amphiphile or by limited proteolysis. Half-maximal inhibition of the activity stimulated by oleic acid or mild tryptic digestion required 8- and 32-times higher concentrations of compound , respectively, compared with the calmodulin-dependent fraction of the ATPase activity. Moreover, calmodulin-independent systems as rabbit skeletal muscle sarcoplasmic reticulum Ca2+-transport ATPase or calf cardiac sarcolemma (Na+ + K+)-transport ATPase are far less influenced by compound as compared with trifluoperazine and calmidazolium. Because of its high specificity compound is proposed to be a promising tool for studying calmodulin-dependent processes. 相似文献
20.
Spinach ferredoxin was modified chemically with trinitrobenzene sulfonic acid (TNBS), a reagent which reacts specifically with amino groups. The trinitrophenylated ferredoxin (TNP-Fd) can accept electrons from Photosystem I as indicated by its full activity in the photoreduction of cytochrome . The modified protein is inactive, however, in the photoreduction of NADP and cannot form a complex with the flavoprotein, ferredoxin: NADP oxidoreductase. The data presented indicate that the inactivity of the modified protein is the result of modification of a single amino group. 相似文献