共查询到20条相似文献,搜索用时 19 毫秒
1.
M. B. Emerit S. El Mestikawy H. Gozlan J. M. Cossery R. Besselievre A. Marquet M. Hamon 《Journal of neurochemistry》1987,49(2):373-380
The synthesis of a tritiated derivative of the 5-HT1A photoaffinity probe 8-methoxy-2-[N-n-propyl, N-3-(2-nitro-4-azidophenyl)aminopropyl]aminotetralin ([3H]8-methoxy-3'-NAP-amino-PAT) allowed the use of this probe for attempting the irreversible labeling of specific binding sites in rat brain membranes. Sodium dodecyl-sulfate-polyacrylamide gel electrophoresis of proteins solubilized from hippocampal microsomal membranes that had been incubated with 20 nM [3H]8-methoxy-3'-NAP-amino-PAT under UV light revealed a marked incorporation of 3H label into a 63-kilodalton protein termed PI. As expected of a possible correspondence between PI and 5-HT1A receptor binding sites, 3H labeling by the photoaffinity probe could be prevented by selective 5-HT1A ligands such as 8-hydroxy-2-(di-n-propylamino)tetralin, ipsapirone, buspirone, and gepirone and by N-ethylmaleimide, but not by the 5-HT2 antagonist ketanserin, noradrenaline- and dopamine-related drugs, monoamine oxidase inhibitors, and chlorimipramine. Furthermore, the regional and subcellular distributions of PI were identical to those of specific 5-HT1A binding sites. These results indicated that the binding subunit of the 5-HT1A receptor is a 63-kilodalton protein with a functionally important sulfhydryl group(s). 相似文献
2.
Miroslawa Kot Wieslawa Zaborska Kinga Orlinska 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):507-516
N-(n-butyl)thiophosphorictriamide (NBPT) and its oxygen analogue N-(n-butyl)phosphorictriamide (NBPTO) were studied as inhibitors of jack bean urease. NBPTO was obtained by spontaneous conversion of NBPT into NBPTO. The conversion under laboratory conditions was slow and did not affect NBPT studies. The mechanisms of NBPT and NBPTO inhibition were determined by analysis of the reaction progress curves in the presence of different inhibitor concentrations. The obtained plots were time-dependent and characteristic of slow-binding inhibition. The effects of different concentration of NBPT and NBPTO on the initial and steady-state velocities as well as the apparent first-order velocity constants obeyed the relationships for a one-step enzyme-inhibitor interaction, qualified as mechanism A. The inhibition constants of urease by NBPT and NBPTO were found to be 0.15 μM and 2.1 nM, respectively. The inhibition constant for NBPT was also calculated by steady-state analysis and was found to be 0.13 μM. NBPTO was found to be a very strong inhibitor of urease in contrast to NBPT. 相似文献
3.
Tangui Maurice Jacques Vignon Jean-Marc Kamenka Robert Chicheportiche 《Journal of neurochemistry》1991,56(2):553-559
The phencyclidine (PCP) derivative, [3H]N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine ([3H]BTCP), was used to label in vivo the dopamine uptake complex in mouse brain. The striatum accumulated the highest level of total and specific binding. Drugs which bind to the dopamine uptake site inhibited [3H]BTCP binding on an order similar to their in vitro affinities for the high-affinity [3H]BTCP site. Drugs which label selectively other monoamine uptake complexes. PCP, or sigma recognition sites were ineffective at doses up to 40 mg/kg. PCP bound to and dissociated from the dopamine uptake complex very rapidly. N-[1-(2-Thienyl)cyclohexyl]pideridine (TCP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) had no effect at any time or at any dose. These results imply that the pharmacological effects of PCP are due to its simultaneous interaction with the dopamine uptake complex and the PCP receptor. Conversely, TCP and MK-801, which have the same behavioral properties as PCP, exert their action only through the interaction with the PCP receptor. 相似文献
4.
O. Suzuki T. Matsumoto M. Oya Y. Katsumata 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,677(2):190-193
N1-Monoacetylspermine, N1,N12-diacetylspermine and N1-monoacetylspermidine were found to be good substrates for rat liver polyamine oxidase, but not for rat liver mitochondrial monoamine oxidase. N8-Monoacetylspermidine, monoacetylcadaverine, monoacetylputrescine and monoacetyl-1,3-diaminopropane were oxidized by the monoamine oxidase when the substrate concentration was 10.0 mM, but not by the polyamine oxidase. All the acetylpolyamines except N1,N12-diacetylspermine were also oxidized by hog kidney diamine oxidase although their affinities for the oxidase appeared low. The present data suggest that acetylpolyamines are not easily metabolized in vivo by either monoamine oxidase or diamine oxidase in mammalian tissues although N1-monoacetylspermine, N1,N12-diacetylspermine and N1-monoacetylspermidine are attacked by polyamine oxidase. 相似文献
5.
R1, a novel repressor of the human monoamine oxidase A 总被引:5,自引:0,他引:5
6.
The effects of glyphosate [N-(phosphonomethyl)glycine] on endogenous in-dole-3-acetic acid (IAA) level, IAA oxidase activity, and possible interactions with alterations in phenolic metabolism have been examined in yellow nutsedge ( Cyperus esculentus L.) plants. IAA was quantified by flame ionization detector gas-chroma-tography, phenols were quantified by high-performance liquid chromatography and the auxin protection and the IAA oxidase activities were determined spectrophoto-metrically and/or polarographically. A significant increase in IAA content was recorded after glyphosate treatment. No IAA oxidase activity was detected in control and treated tissues. Auxin protection activity and gentisic acid were present in all extracts assayed, and their concentrations increased as the rate of glyphosate application increased. Addition of gentisic acid to an extract of control plants increased the auxin protection detected. These findings indicate that the high levels of free IAA in yellow nutsedge leaves after glyphosate application are due to the inhibition of the IAA oxidase activity by increased levels of the IAA-protecting phenol gentisic acid. 相似文献
7.
To develop an enzymatic measurement of HbA(1C), two key enzymes, i.e., fructosyl peptide oxidase and Aspergillus protease were characterized. Fructosyl peptide oxidase from Eupenicillium terrenum was a flavoenzyme that could catalyze the oxidation of N-(1-deoxyfructosyl)-Val-His. The enzyme showed high specificity toward alpha-glycated molecules, therefore it seemed suitable for the HbA(1C) assay. Since high levels of FPOX expression seemed toxic to host cells, we applied a gene expression system using a bacteriophage vector and achieved high levels of expression in Escherichia coli. Next, we found that Aspergillus protease was able to digest N-(1-deoxyfructosyl)-hexapeptide, a glycated peptide that was released from the beta-chain of HbA(1C) by Glu-C endoproteinase. We showed that the N-(1-deoxyfructosyl)-Val-His released from N-(1-deoxyfructosyl)-hexapeptide by Aspergillus protease could be assayed enzymatically using fructosyl peptide oxidase, therefore these enzymes could be applied to the enzymatic measurement of HbA(1C). 相似文献
8.
Eiki Kominami Seiichi Hashida Nobuhiko Katunuma 《Biochemical and biophysical research communications》1980,93(3):713-719
When injected into rats, leupeptin and E-64 (N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]agmatine), potent thiol protease inhibitors of microbial origin, inhibited cathepsin B (EC 3.4.22.1) and cathepsin L (EC 3.4.22.-) in the lysosomal fraction of liver. Both compounds strongly inhibited cathepsin B, but E-64 had more effect than leupeptin on cathepsin L. Neither compound inhibited cathepsin D (EC 3.4.23. 5). E-64 reduced the apparent turnover rate of aldolase (EC 4. 1.2.13) markedly and the turnover rates of lactic dehydrogenase (EC 1.1.1.27) and total soluble protein slightly. Leupeptin had apparently less effect on degradation of those enzymes, but significant effect on degradation of aldolase. These results indicate that proteinases, which are sensitive to inhibition by E-64 or leupeptin, especially cathepsin L and cathepsin B may be important in degradation of aldolase. 相似文献
9.
《Bioscience, biotechnology, and biochemistry》2013,77(6):1256-1260
Hydroxyurea (HU, NH2CONHOH), or hydroxycarbamide, is a hydroxamic acid derivative used as a drug for anti-neoplasm and sickle-cell disease. In this study, HU was found to have antioxidant activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals and dose-dependent inhibitory activities against monoamine oxidase (MAO)-A, MAO-B, and semicarbazide-sensitive amine oxidase (SSAO) as compared to controls of clorgyline, deprenyl, and semicarbazide respectively. HU showed mixed-type, competitive-type, and competitive-type inhibition, respectively, with respect to substrates of MAO-A, MAO-B, and SSAO with apparent inhibition constants (Ki) of 19.46, 5.38, and 1.84 μM. 相似文献
10.
Chandra Shekhar K. Mayanil Najma Z. Baquer 《Biochimica et Biophysica Acta (BBA)/General Subjects》1983,757(2):151-155
Increasing concentrations of dopamine fail to give a biphasic response to (Na+ + K+)-ATPase activity in various subcellular fractions of rat brain preincubated with monoamine oxidase inhibitors, viz. 1·10?4 M clorgyline and 1·10?4 M deprenyl. The product of the monoamine-oxidase-catalysed reaction with dopamine as substrate is 3-methoxy-4-hydroxyphenylacetaldehyde. An analogue of this product is 3-methoxy-4-hydroxybenzaldehyde. This analogue, when incubated with the subcellular fractions which had been preincubated with monoamine oxidase inhibitors and dopamine, gave a more pronounced biphasic response to (Na+ + K+)-ATPase activity than that observed in the fractions incubated with dopamine alone. 相似文献
11.
Shigeru Satoh Naoko Oyamada Toshihito Yoshioka Naoki Midoh 《Plant Growth Regulation》1997,23(3):191-193
The effects of 1,1-dimethyl-4-(phenylsulfonyl)semicarbazide (DPSS) on the in vitro activities of 1-aminocyclopropane-1-carboxylate (ACC) oxidase and ACC synthase isolated from senescing carnation petals were investigated. In contrast to a previous proposal, DPSS at 1 mM did not inhibit the in vitro activity of ACC oxidase. It was confirmed that DPSS does not inhibit ACC synthase activity. DPSS probably does not exert its inhibitory action on ethylene production by a direct action on ACC oxidase and ACC synthase, but by some unknown action. 相似文献
12.
Nutan T. Patel Richard R. Fritz Creed W. Abell 《Biochemical and biophysical research communications》1984,125(2):748-754
Monoamine oxidase B was purified from human liver mitochondria using a monoclonal antibody, MAO B-1C2, which recognizes monoamine oxidase B but not A. Triton X-100 extracts of mitochondria were incubated with purified MAO B-1C2 (IgG1), and the catalytically active enzyme:antibody complex was isolated by affinity chromatography on Protein A-Sepharose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the complex revealed the presence of four polypeptide bands (monoamine oxidase B, 57,900 dalton; antibody heavy chain, 52,200 dalton; and two light chains, 29,400 and 27,700 dalton), and indicated a 1:1 stoichiometric ratio of enzyme to antibody. This method gave 154-fold purification of the enzyme from mitochondria. 相似文献
13.
M. Tenne J. P. M. Finberg M. B. H. Youdim S. Ulitzur 《Journal of neurochemistry》1985,44(5):1378-1384
The in vivo luminescence of an aldehyde-requiring mutant of the luminous bacteria Vibrio harveyi (M42) increases dramatically upon the addition of long-chain aliphatic aldehydes (C8-C16). The intensity of this luminescence is linearly related to aldehyde concentration. This property was utilized for the determination of monoamine oxidase activity using n-octylamine and n-decylamine as substrates, which are converted by monoamine oxidase to n-octylaldehyde and n-decylaldehyde, respectively. The addition of the amine to a suspension containing rat liver mitochondria and M42 cells initiated a luminescence that was directly proportional to monoamine oxidase activity according to two parameters: (1) the rate of the initial increase in luminescence and (2) the final "steady-state" level of luminescence. The new assay has advantages of high sensitivity, rapidity, the possibility to perform discontinuous as well as continuous monitoring of monoamine oxidase activity, and applicability to turbid preparations. 相似文献
14.
M W Dudley 《Life sciences》1988,43(23):1871-1877
Inhibition of monoamine oxidase A through pretreatment of rats with clorgyline (10 mg/kg ip) or the pro-drug MDL 72,394 (0.5 mg/kg ip) did not block the amine-depleting action of xylamine (25 mg/kg ip). Xylamine treatment resulted in a loss of approximately 60% of the control level of norepinephrine in the cerebral cortex. A 1-hr pretreatment, but not a 24-hr pretreatment, with the monoamine oxidase B inhibitor, L-deprenyl (10 mg/kg ip), prevented the depletion of norepinephrine by xylamine. In addition, pretreatment with MDL 72,974 (1.25 mg/kg ip), a monoamine oxidase B inhibitor without amine-releasing or uptake - inhibiting effects, did not protect cortical norepinephrine levels. Inhibition of monoamine oxidase by either MDL 72,974 or MDL 72,394 did not prevent the inhibition of [3H]norepinephrine uptake into rat cortical synaptosomes by xylamine. These data indicate that monoamine oxidase does not mediate the amine-releasing or uptake inhibiting properties of xylamine. The protection afforded by L-deprenyl following a 1-hr pretreatment most probably was due to accumulation of its metabolite, L-amphetamine, which would inhibit the uptake carrier. A functional carrier is required for depletion since desipramine (20 mg/kg ip) administered 1 hr prior to xylamine, was also able to prevent depletion of norepinephrine. 相似文献
15.
I S Severina 《Biokhimii?a (Moscow, Russia)》1975,40(2):423-431
Functional groups of mitochondrial monoamine oxidase critical for monoamine oxidase activity were investigated by chemical modification of highly purified monoamine oxidase preparations from pig liver by specific inhibitors. The substrate and inhibitory properties of synthesized derivatives of beta-phenylethylamine, containing various acylating and alkylating groups in the p-position of the benzene ring, were studied. It was shown that 4-carbmethoxy-beta-phenylethylamine (I) is readily deaminated by monoamine oxidase, whereas 4-O-acetyl-beta-phenylethylamine (II) is not affected by the enzyme. 4-O-acetyl-beta-phenylethylamine (II) and 4-ethyl-O-chloroacethyl phenol (III) inhibit deamination of tyramine, 4-amino-beta-phenylethylamine, beta-phenylethylamine, 4-chloro-beta-phenylethylamine and serotonin in different degrees. The kinetic studies demonstrated that this inhibition is probably due to the acylating properties of the compounds obtained. Selectivity in inhibition may be accounted for by acylation of the group of monoamine oxidase which is located in the nearest proximity to the nucleophynoamine oxidase which is located in the nearest proximity to the nucleophylic site of monoamine oxidase active centre important for binding of tyramine. This group is neither the imidazole group of histidyl, nor the SH-group of cysteinyl residues of monoamine oxidase protein molecule. Its nature is discussed in the light of the data obtained. 相似文献
16.
S Ottoboni P Caldera A Trevor N Castagnoli 《The Journal of biological chemistry》1989,264(23):13684-13688
Kinetic deuterium isotope effects for the noncompetitive, intermolecular monoamine oxidase B-catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the corresponding 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+ were found to be 3.55 on Vmax and 8.01 on Vmax/Km with MPTP-6,6-d2 as the deuterated substrate. Similar values were obtained with MPTP-2,2,6-d4 and MPTP-CD3-2,2,6,6-d4. The deuterium isotope effect for the electrochemical oxidation of 1 mM MPTP-2,2,6,6-d4 was only 1.35. These results indicate that the monoamine oxidase B-catalyzed oxidation of this substrate may not proceed via a reaction pathway involving alpha-carbon deprotonation of an aminium radical intermediate. Isotope effect measurements also established that the rate of inactivation of monoamine oxidase B by MPTP is unaffected by replacement of the C-6 methylene protons with deuterons, but is retarded by replacement of the C-2 methylene protons (DKi = 1.9). The mechanism-based inactivation of monoamine oxidase B by MPTP, therefore, is likely to mediated by a species derived from the enzyme-generated 2,3-dihydropyridinium oxidation product. 相似文献
17.
Stimulation by D-glucose of mitochondrial oxidative events in islet cells. 总被引:1,自引:0,他引:1
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Antibodies were elicited to FAD by using the hapten N-6-(6-aminohexyl)-FAD conjugated to the immunogenic carrier protein bovine serum albumin. Cross-reactivity was determined by Ouchterlony double-diffusion analysis with N-6-(6-aminohexyl)-FAD coupled to rabbit serum albumin. Anti-FAD IgG was partially purified by (NH4)2SO4 precipitation followed by DEAE-cellulose/CM-cellulose and bovine serum albumin-agarose chromatography. The partially purified anti-FAD IgG fraction failed to inhibit the catalytic activities of the flavin-containing enzymes nitrate reductase, xanthine oxidase and succinate dehydrogenase, whereas enzyme activity could be inhibited by addition of antibodies elicited against the native proteins. However, the partially purified anti-FAD IgG fraction could be used as a highly sensitive and specific probe to detect proteins containing only covalently bound flavin, such as succinate dehydrogenase, p-cresol methylhydroxylase and monoamine oxidase, by immuno-blotting techniques. Detection limits were estimated to be of the order of femtomolar concentrations of FAD with increased sensitivity for the 8 alpha-N(3)-histidyl linkage compared with 8 alpha-O-tyrosyl substitution. 相似文献
18.
Inhibition of amine oxidases activity by 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives
Manna F Chimenti F Bolasco A Secci D Bizzarri B Befani O Turini P Mondovi B Alcaro S Tafi A 《Bioorganic & medicinal chemistry letters》2002,12(24):3629-3633
A novel series of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesised and investigated for the ability to inhibit selectively monoamine oxidases, swine kidney oxidase, and bovine serum amine oxidase. The newly synthesised compounds 1–6 proved to be reversible and non-competitive inhibitors of all types of the assayed amine oxidases. Compounds inhibit monoamine oxidases potently, displaying low I50 values of particular interest. In particular 1-acetyl-3-(2,4-dihydroxyphenyl)-5-(3-methylphenyl)-4,5-dihydro-(1H)-pyrazole 6 showed to be a potent monoamine oxidase inhibitor with a Ki of about 10−8 M. Further insights in the theoretical evaluation of the possible interactions between the compounds and monoamine oxidase B have been developed through a computational approach. 相似文献
19.
Photoinactivation of B-type monoamine oxidase by a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolite 总被引:1,自引:0,他引:1
The reaction of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) with monoamine oxidase from a variety of tissues including rat and monkey brain, bovine liver, and human placenta and platelets was found to yield, as a primary product, a reactive photosensitive substance with an absorbance maximum at 345 nm which is not the cation 1-methyl-4-phenylpyridinium ion previously reported as a monoamine oxidase-MPTP metabolite in vivo and in vitro. Our results suggest that the 1-methyl-4-phenyl-pyridinium ion is probably only generated in subsequent nonenzymatic transformations of this reactive monoamine oxidase metabolite. This substance was found to specifically inactivate the B-form of monoamine oxidase by a photo-induced mechanism and to react directly with NADPH and dopamine. Properties of the metabolite and potential significance of its reactions to MPTP neurotoxicity are discussed. 相似文献
20.
Inhibition of monoamine oxidase by substituted hydrazines 总被引:1,自引:1,他引:0
Keith F. Tipton 《The Biochemical journal》1972,128(4):913-919
1. The initial rate of inhibition of monoamine oxidase by phenethylhydrazine was shown to be similar, in pH-dependence and kinetic properties, to the oxidation of that compound by monoamine oxidase. 2. The time-course of irreversible inhibition of monoamine oxidase by phenethylhydrazine lags behind that of reversible inhibition. 3. Hydralzine was shown to be a reversible competitive inhibitor of monoamine oxidase, but phenylhydrazine is an irreversible inhibitor. Inhibition by the latter compound is not affected by the absence of oxygen, and the presence of substrate exerts no protective action. 4. Hydrazine does not inhibit monoamine oxidase unless a substrate and oxygen are present. 5. Phenethylidenehydrazine was found to be a time-dependent inhibitor of monoamine oxidase and the rate of inhibition was hindered by increasing oxygen concentration. 6. A mechanism for the inhibition of the enzyme by phenethylhydrazine is proposed in which the product of oxidation of this compound is a potent reversible inhibitor and an irreversible inhibitor of the enzyme. A computer simulation of such a mechanism predicts time-courses of inhibition that are in reasonable agreement with those observed experimentally. 相似文献