首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 421 毫秒
1.
The physiological and biochemical basis for quinclorac resistance in a false cleavers (Galium spurium L.) biotype was investigated. There was no difference between herbicide resistant (R) and susceptible (S) false cleavers biotypes in response to 2,4-D, clopyralid, glyphosate, glufosinate-ammonium, or bentazon. On the basis of GR(50) (growth reduction of 50%) or LD(50) (lethal dose to 50% of tested plants) values, the R biotype was highly resistant to the acetolactate synthase (ALS) inhibitor, thifensulfuron-methyl (GR(50) resistance ratio R/S = 57), and quinolinecarboxylic acids (quinclorac R/S = 46), resistant to MCPA (R/S = 12), and moderately resistant to the auxinic herbicides picloram (R/S = 3), dicamba (R/S = 3), fluroxypyr (R/S = 3), and triclopyr (R/S = 2). The mechanism of quinclorac resistance was not due to differences in [(14)C]quinclorac absorption, translocation, root exudation, or metabolism. Seventy-two hours after root application of quinclorac, ethylene increased ca. 3-fold in S but not R plants when compared to controls, while ABA increased ca. 14-fold in S as opposed to ca. 3-fold in R plants suggesting an alteration in the auxin signal transduction pathway, or altered target site causes resistance in false cleavers. The R false cleavers biotype may be an excellent model system to further examine the auxin signal transduction pathway and the mechanism of quinclorac and auxinic herbicide action.  相似文献   

2.
Three diclofop-methyl (DM) resistant biotypes of Lolium rigidum (R1, R2, and R3) were found in different winter wheat fields in Spain, continuously treated with DM, DM + chlortoluron, or DM + isoproturon. Herbicide rates that inhibited shoot growth by 50% (ED50) were determined for DM. There were found that the different biotypes exhibited different ranges of resistance to this herbicide; the resistant factors were 7.2, 13, and 36.6, respectively. DM absorption, metabolism, and effects on ACCase isoforms were examined in these biotypes of L. rigidum. The most highly resistant, biotype R3, contained an altered isoform of ACCase. In biotype R2, which exhibited a medium level of resistance, there was an increased rate of oxidation of the aryl ring of diclofop, a reaction most likely catalyzed by a cytochrome P450 enzyme. In the other biotype, R1, DM penetration was significantly less than that observed in the resistant (R2 and R3) and susceptible (S) biotypes. Analysis of the leaf cuticle surface by scanning electron microscopy showed a greater epicuticular wax density in the leaf cuticles of biotype R1 than in the other biotypes.  相似文献   

3.
Whole-plant response of two suspected resistant Avena fatua biotypes from Chile and Mexico to ACCase-inhibiting herbicides [aryloxyphenoxypropionate (APP), cyclohexanedione (CHD), and pinoxaden (PPZ)] and the mechanism behind their resistance were studied. Both dose-response and ACCase enzyme activity assays revealed cross-resistance to the three herbicide families in the biotype from Chile. On the other hand, the wild oat biotype from Mexico exhibited resistance to the APP herbicides and cross-resistance to the CHD herbicides, but no resistance to PPZ. Differences in susceptibility between the two biotypes were unrelated to absorption, translocation, and metabolism of the herbicides. PCR generated fragments of the ACCase CT domain spanning the potential mutations sited in the resistant and susceptible biotypes were sequenced and compared. A point mutation was detected in the aspartic acid triplet at the amino acid position 2078 in the Chilean biotype and in isoleucine at the amino acid position 2041 in the Mexican wild oat biotype, which resulted in a glycine triplet and an asparagine triplet, respectively. On the basis of in vitro assays, the target enzyme (ACCase) in these resistant biotypes contains a herbicide-insensitive form. This is the first reported evidence of resistance to pinoxaden in A. fatua.  相似文献   

4.
Digitaria insularis biotypes resistant to glyphosate have been detected in Brazil. Studies were carried out in controlled conditions to determine the role of absorption, translocation, metabolism, and gene mutation as mechanisms of glyphosate resistance in D. insularis. The susceptible biotype absorbed at least 12% more (14)C-glyphosate up to 48 h after treatment (HAT) than resistant biotypes. High differential (14)C-glyphosate translocation was observed at 12 HAT, so that >70% of the absorbed herbicide remained in the treated leaf in resistant biotypes, whereas 42% remained in the susceptible biotype at 96 HAT. Glyphosate was degraded to aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine by >90% in resistant biotypes, whereas a small amount of herbicide (up to 11%) was degraded by the susceptible biotype up to 168 HAT. Two amino acid changes were found at positions 182 and 310 in EPSPS, consisting of a proline to threonine and a tyrosine to cysteine substitution, respectively, in resistant biotypes. Therefore, absorption, translocation, metabolism, and gene mutation play an important role in the D. insularis glyphosate resistance.  相似文献   

5.
Under controlled-environment conditions, ethametsulfuron-methyl doses that inhibited growth by 50% (ED(50)) were >100 and <1 g of active ingredient (ai) ha(-)(1) for ethametsulfuron-methyl-resistant (R) and -susceptible (S) wild mustard, respectively. There were no differences between the two biotypes with regard to absorption and translocation of the herbicide. Three days after treatment, approximately 90, 5, and 2% of the applied [(14)C]ethametsulfuron-methyl was found in the treated leaf, foliage, and roots of each biotype, respectively. Acetolactate synthase extracted from the two biotypes was equally sensitive to both ethametsulfuron-methyl and chlorsulfuron. These results indicate that resistance was not due to differences in the target site, absorption, or translocation. However, ethametsulfuron-methyl was metabolized more rapidly in the R than the S biotype. Approximately 82, 73, 42, 30, and 17% of the recovered radioactivity remained as ethametsulfuron-methyl in R wild mustard 3, 6, 18, 48, and 72 h after treatment, respectively. Conversely, 84, 79, 85, and 73% of the (14)C was ethametsulfuron-methyl in the S biotype 12, 24, 48, and 72 h after treatment, respectively. On the basis of these results, it is proposed that resistance is due to enhanced metabolism of ethametsulfuron-methyl in the R biotype.  相似文献   

6.
Experiments were conducted to determine the inheritance and physiological basis for resistance to the synthetic auxinic herbicide (2,4-dichlorophenoxy)acetic acid (2,4-D) in a prickly lettuce biotype. Inheritance of 2,4-D resistance in prickly lettuce is governed by a single codominant gene. Absorption and translocation were conducted using (14)C-2,4-D applied to 2,4-D-resistant and -susceptible biotypes. At 96 h after treatment (HAT), the resistant biotype absorbed less applied 2,4-D and retained more 2,4-D in the treated portion of the leaf compared to the susceptible biotype. The resistant biotype translocated less applied 2,4-D to leaves above the treated leaf and crown at 96 HAT compared to the susceptible biotype. No difference in the rate of metabolism of 2,4-D was observed between the two biotypes. Resistance to 2,4-D appears to originate from a reduced growth deregulatory and overstimulation response compared to the susceptible biotype, resulting in lower translocation of 2,4-D in the resistant prickly lettuce biotype.  相似文献   

7.
Acetyl-coenzyme A carboxylase (ACCase) isozymes were separated from cyclohexanedione-resistant and -susceptible maize. ACCase240 from resistant maize was 3.7-, >77-, and 12.8-fold more resistant to inhibition by clethodim, sethoxydim, and tralkoxydim, respectively, than ACCase240 from susceptible maize. The resistant ACCase240 preparation had 3.0-fold more protein and 14.5-fold lower specific activity than susceptible ACCase240. Resistant ACCase240 has a V(max) 5.5-fold lower than that of susceptible ACCase240, whereas apparent K(m) values were similar. ACCase220 from resistant maize was >25- and 7.2-fold more resistant to inhibition by sethoxydim and tralkoxydim, respectively, than susceptible ACCase220 but was inhibited to the same extent by clethodim. In summary, sethoxydim-resistant corn has an altered herbicide-resistant ACCase220 isozyme and increased expression of a less efficient, herbicide-resistant ACCase240 isozyme. However, to what extent alteration of both isozymes contributes to sethoxydim resistance is not clear.  相似文献   

8.
A field survey was conducted for the sampling of Acetyl-CoA carboxylase (ACCase) inhibitor resistance littleseed canarygrass, a major weed of wheat, from Punjab, Pakistan in 2014 for confirmation of resistance. The surveyed regions encompassed four different cropping systems including rice–wheat, maize–wheat, cotton–wheat and mixed cropping. Dose–response assay was conducted for confirmation of resistance. Efficacy of herbicide mixtures including clodinafop–propargyl, metribuzin, pinoxaden and sulfosulfuron at a range of doses was investigated to manage littleseed canarygrass. Results revealed that all populations were resistant to fenoxaprop except PM-BWL-2. The higher level resistance (6.5) was found in populations collected from rice–wheat cropping system. The tested herbicide mixtures at 75% and 100% of the recommended dose of each mixture component provided the effective control of resistant littleseed canarygrass. Mixtures at 50% provided more than 80% control and reduced growth and seed production potential of surviving plants. The confirmation of ACCase inhibitor resistance as the first case of herbicide resistance in Pakistan, leads us to discourage use of ACCase inhibitor herbicides alone. However, herbicide mixtures at 75% and 100% of the recommended dose are suggested to manage this weed for sustainable wheat production in the surveyed cropping systems.  相似文献   

9.
Evolution of toxicity upon hydrolysis of fenoxaprop-p-ethyl   总被引：2，自引：0，他引：2  
Hydrolysis of fenoxaprop-p-ethyl (FE), a widely used herbicide, was studied in aqueous buffer solutions at pH ranging from 4.0 to 10.0. The degradation kinetics, strongly dependent on pH values, followed first-order kinetics. FE was relatively stable in neutral media, whereas it degraded rapidly with decreasing or increasing pH. In acidic conditions (pH = 4, 5), the benzoxazolyl-oxy-phenyl ether linkage of FE was cleaved to form ethyl 2-(4-hydroxyphenoxy)propanoate (EHPP) and 6-chloro-2,3-dihydrobenzoxazol-2-one (CDHB). While in basic conditions (pH = 8, 9, 10), herbicidal activity fenoxaprop-p (FA) was formed via breakdown of the ester bond of the herbicide. Both the two pathways were concurrent in neutral conditions (pH = 6, 7). Toxicity studies on Daphnia magna showed that FE was most toxic to D. magna with 48 h EC(50) of 14.3 micromol/L, followed by FA (43.8 micromol/L), CDHB (49.8 micromol/L), and EHPP (333.1 micromol/L). Mode of toxic action analysis indicated that EHPP exhibited toxicity via polar narcosis, whereas CDHB belonged to reactive acing compound. The mixture toxicity of CDHB and EHPP was nonadditive and can be predicted by a response addition model. Therefore, the evaluation of overall FE toxicity to D. magna in the aquatic systems needs to consider the degradation of FE.  相似文献   

10.
To identify proteins that may be involved in mediating auxinic herbicide resistance (i.e., resistance to dicamba, picloram, 2,4-D), we compared the proteomes of an auxinic-herbicide-susceptible (S) and -resistant (R) wild mustard (Sinapis arvensis L.) biotype at different developmental stages. Using two-dimensional electrophoresis and mass spectrometry, we identified 11 seedling and leaf proteins that showed reproducible differences in expression between the S and the R wild mustard biotype following application of dicamba. Our proteome-level studies revealed the increased expression of the enzyme peptidylprolyl cis-trans isomerase (PPIase), which has recently been implicated in auxin signal transduction. Juglone, an inhibitor of PPIase, interfered with the normal ability of R seeds to germinate in the presence of dicamba, whereas S seeds did not germinate in the presence of dicamba or dicamba plus juglone. When R and S plants (3-4 leaf stage) were treated with dicamba, S showed typical auxinic herbicide effects (e.g., epinasty) whereas R did not. However, the concomitant application of dicamba and juglone to greenhouse-grown R plants produced morphological changes that were consistent with known auxinic-herbicide-induced symptoms. This is the first report suggesting the potential involvement of differential expression of PPIase in mediating auxinic herbicide resistance.  相似文献   

11.
The photodegradation pathway of the commonly used herbicide fenoxaprop-p-ethyl (FE) was elucidated, and the effects of the photodegradation on its toxicity evolution were investigated. Under solar irradiation, FE could undergo photodegradation, and acetone enhanced the photolysis rates significantly. The same photoproducts formed under the irradiation of lambda > 200 nm and lambda > 290 nm through rearrangement, loss of ethanol after rearrangement, de-esterification, dechlorination, photohydrolysis, and the breakdown of the ether linkages. One of the main transformation products, 4-[(6-chloro-2-benzoxazolyl)oxy] phenol (CBOP), was resistant to photodegradation under the irradiation of lambda > 290 nm, and its photolysis rate was seven times slower than the parent under the irradiation of lambda > 200 nm. Among the metabolites, CBOP (48 h EC50 of 1.49-1.64 mg/L) and hydroquinone (48 h EC50 of 0.25-0.28 mg/L) were more toxic to Daphnia magna than the parent FE (48 h EC50 of 4.2-6.9 mg/L). Thus, more toxic and photoresistant products were generated from photolysis of the herbicide. Ecotoxicological effects of phototransformed products from pesticides should be emphasized for the ecological risk assessment of these anthropogenic pollutants.  相似文献   

12.
Similarities and differences between steric and electrostatic potentials of a monoclonal-antibody-based surrogate of a herbicide target-site and its in vitro enzyme target were investigated using three-dimensional quantitative structure-activity relationship comparative molecular field analysis (3D-QSAR CoMFA). Two separate, five-component, partial least squares CoMFA models were developed to compare the interaction of cyclohexanedione herbicides with their target site, acetyl coenzyme-A carboxylase (ACCase; EC 6.4.1.2) and a cyclohexanedione pharmacophore-specific monoclonal antibody (mAb A). On the basis of CoMFA models, similarities in steric and electrostatic requirements around position 2 of the binding site for the oxime functional group of the cyclohexanedione molecule appear to be crucial for interaction of the herbicide with both ACCase and mAb A. These similarities explain the observed quantitative relationship between binding of cyclohexandedione herbicides to ACCase mAb A. Furthermore, these results support the production and use of mAb-based surrogates of pesticide targets as screening tools in pesticide discovery programs.  相似文献   

13.
De-esterification is an initial step in the metabolism of certain herbicides, for example, fenoxaprop-ethyl [(+/-)-ethyl 2-[4-[(6-chloro-2-benzoxaolyl)oxy]phenoxy]propanoate] (FE). The ethyl-ester bond cleavage of FE to fenoxaprop acid (FA) by purified enzymes, crude bacterial enzyme preparations, and soils was investigated. In similar experiments fluorescein diacetate (FDA) was used as an alternative substrate. FE stability was pH sensitive in acidic buffered solutions; that is, below pH 4.6, rapid nonenzymatic hydrolysis of the benzoxazolyl-oxy-phenoxy ether linkage occurred, forming 6-chloro-2,3-dihydro-benzoxazol-2-one (CDHB) and ethyl 4-hydroxyphenoxypropanoate or 4-hydroxyphenoxypropanoate. With porcine esterase and cell-free Pseudomonas fluorescens extracts, activity on FE and FDA was most rapid at pH 7.6-8.6 but decreased 80-90% at pH 5.6. Yeast (Candida cylindrica) lipase-mediated de-esterification of FE and FDA was not as sensitive to pH; that is, activity at pH 4.6 was 70% of that at pH 7.6. Short-term incubations (20 h) were conducted in eight soils (pH 4.5-6.9) treated with (14)C-chlorophenyl ring-labeled FE (2 mg kg(-)(1)). In the most acidic soils (pH 4.4-4.5) 25% of the (14)C was recovered as FA, versus 30-40% in moderately acid soils (pH 5.0-5.6) and 55% in neutral soils (pH 6.8-6.9). There was a similar correlation between soil pH and FDA de-esterification. CDHB was formed in all acidic soils with levels 4-fold greater in pH 4.4-4.5 soils than in pH 5. 0-5.6 soils. CDHB was not formed in neutral soils. Results demonstrate some chemical hydrolysis (benzoxazolyl-oxy-phenoxy ether linkage) of FE in acid soils, the sensitivity of enzymatic de-esterification of FE to pH, and the potential of FDA as a colorimetric indicator for esterase hydrolysis of FE.  相似文献   

14.
The aryloxyphenoxypropionic acid (AOPP) and cyclohexanedione (CHD) herbicides inhibit the first committed enzyme in fatty acid biosynthesis, acetyl CoA carboxylase (ACCase). The frequent use of AOPP and CHD herbicides has resulted in the development of resistance to these herbicides in many grass weed species. New herbicides that inhibit both the susceptible and resistant forms of ACCase in grass weeds would have obvious commercial appeal. In the present study, an attempt was made to identify molecules that target both the herbicide-sensitive and -resistant forms of ACCase. Seven experimental compounds, either CHD-like or AOPP-CHD hybrids, were synthesized and assayed against previously characterized susceptible and resistant forms of ACCase. All seven compounds inhibited ACCase from sensitive biotypes of Setaria viridis and Eleusine indica (I50 values from 6.4 to >100 microM) but were not particularly potent compared to some commercialized herbicides (I50 values of 0.08-5.6 microM). In almost all cases, the I50 values for each compound assayed against the resistant ACCases were higher than those against the corresponding sensitive ACCase, indicating reduced binding to the resistant ACCases. One compound, a CHD analogue, was almost equally effective against the resistant and susceptible ACCases, although it was not a very potent ACCase inhibitor per se (I50 of 51 and 76 microM against susceptible ACCase from S. viridis and E. indica, respectively). The AOPP-CHD hybrid molecules also inhibited some of the resistant ACCases, with I50 values ranging from 6.4 to 50 microM. These compounds may be good leads for developing ACCase inhibitors that target a wider range of ACCase isoforms, including those found in AOPP- and CHD-resistant weed biotypes.  相似文献   

15.
The physiological basis for MCPA resistance in a hemp-nettle (Galeopsis tetrahit L.) biotype, obtained from a MCPA-resistant field population, was investigated. Dose-response studies revealed that the resistance factor for MCPA, based on GR50 comparisons of total dry weight of resistant (R) and susceptible (S) plants, was 3.3. Resistance factors for fluroxypyr, dicamba, 2,4-D, glyphosate, and chlorsulfuron were 8.2, 1.7, 1.6, 0.7, and 0.6, respectively. MCPA resistance was not due to differences in absorption, because both R and S biotypes absorbed 54% of applied [14C]MCPA 72 h after treatment. However, R plants exported less (45 vs 58% S) recovered 14C out of treated leaves to the apical meristem (6 vs 13% S) and root (32 vs 38% S). In both biotypes, approximately 20% of the 14C recovered in planta was detected as MCPA metabolites. However, less of the 14C recovered in the roots of R plants was MCPA. Therefore, two different mechanisms protect R hemp-nettle from MCPA phytotoxicity: a lower rate of MCPA translocation and a higher rate of MCPA metabolism in the roots. In support of these results, genetic studies indicated that the inheritance of MCPA resistance is governed by at least two nuclear genes with additive effects.  相似文献   

16.
Picloram resistance exhibited by transgenic tobacco (Nicotiana tabacum) plants expressing an anti-picloram single-chain variable fragment (scFv) antibody was investigated through the study of homozygous lines expressing the antibody. Dose-response bioassays, using foliar application of picloram, showed that these homozygous transgenic plants were resistant to at least 5 g of ai ha-1 picloram and grew normally to produce seed, whereas wild-type plants did not survive. Although these lines had improved resistance compared with those previously reported, significant improvements are still required to achieve field-level resistance. Uptake and translocation studies demonstrated that [14C]picloram translocation from treated leaves to the apical meristem was reduced in transgenic versus wild-type plants. The presence of [14C]picloram visualized by autoradiography and quantified by liquid scintillation spectrometry, demonstrated the distribution of more picloram in the treated leaf and less in the apical meristem of transgenic plants when compared to wild-type plants. No differences between transgenic and wild-type plants were found in the distribution of [14C]clopyralid, a herbicide with structural similarity to picloram as well as the same mechanism of action. No differences were found in the metabolism of [14C]picloram. Taken together, these results suggest that reduced translocation to the site of action is a major mechanism responsible for picloram resistance in tobacco plants expressing this anti-picloram antibody.  相似文献   

17.
Thirty-nine wheat accessions were used to evaluate their extract phytotoxicity against annual ryegrass (Lolium rigidum Gaud.). Aqueous extracts of wheat shoot residues significantly inhibited the germination and root growth of a biotype of annual ryegrass resistant to herbicides of acetyl CoA carboxylase inhibitors (group A), acetolactate synthase inhibitors (B), photosystem II inhibitors (C), and tubulin formation inhibitors (D). The germination of the herbicide resistant (HR) biotype was inhibited by 3-100%, depending upon the wheat accession. The phytotoxic effects on ryegrass root growth ranged from 12% stimulation to 100% inhibition, compared to a control. The germination and root growth of a herbicide-susceptible (HS) biotype of annual ryegrass were also inhibited by the wheat extracts, with germination inhibited by 4-100%, and root growth by 19-100%. Bioassays with two known wheat allelochemicals showed that p-coumaric acid and propionic acid significantly inhibited the growth of both HR and HS biotypes of annual ryegrass. The two compounds completely inhibited the root growth of HR ryegrass at concentrations greater than 5.0 mM. In comparison with p-coumaric acid, propionic acid was more inhibitory to seed germination, shoot, and root growth of both ryegrass biotypes. The root growth of the HR biotype was more sensitive when exposed to wheat extracts, to p-coumaric acid, and to propionic acid. The results suggest that residues of certain wheat cultivars with strong allelopathic potential could provide a nonherbicidal alternative for the management of herbicide-resistant weed species.  相似文献   

18.
Cyclohexanediones, aryloxyphenoxypropionates, indolizidinediones, and triazinediones are four known structural classes of herbicides that inhibit acetyl coenzyme-A carboxylase (ACCase; EC 6.4.1.2). An immunological study to determine the potential of ACCase inhibitor-specific monoclonal antibodies as screening tools to identify novel lead chemistry was undertaken. Using two cyclohexanedione-specific monoclonal antibodies (mAb A and mAb B; Webb, S. R.; Hall, J. C. J. Agric. Food Chem. 2000, 48, 1210-1218) and three different cyclohexanedione hapten coating conjugates, competitive indirect enzyme-linked immunosorbent assays (ciELISA) were developed. Cross-reactivity of the monoclonal antibodies with four structural classes of ACCase inhibitors revealed that the ciELISA using mAb A and a modified cyclohexanedione hapten coating conjugate detected analogues from all four known classes of ACCase inhibitors. A pilot screen using this ciELISA format identified two novel ACCase inhibitors, demonstrating the potential for antibodies as rapid and cost-effective screening tools for identifying novel lead chemistry in pesticide discovery programs.  相似文献   

19.
A recently developed HPTLC/UV-FLD method was compared to the routinely used HPLC/UV-FLD method for the quantification of heterocyclic aromatic amines (HAA) formed at trace levels during the heating process of meat. For formation of these process contaminants under normal cooking conditions, beef patties were fried in a double-contact grill at 230 degrees C for five different frying times and extracted by solid-phase extraction. The HAAs most frequently found, that is, 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5- f]quinoxaline (4,8-DiMeIQx), 9 H-pyrido[3,4- b]indole (norharman), and 1-methyl-9 H-pyrido[3,4- b]indole (harman), were quantified by two chromatographic methods, which were orthogonal to each other (normal versus reversed phase system). Both methods showed a similar performance and good correlation of the results ( R (2) between 0.8875 and 0.9751). The comparison of running costs and run time in routine analysis proved HPTLC/UV-FLD to be more economical (factor of 3) and faster (factor of 4) due to its capability of parallel chromatography. The HAA findings calculated by standard addition increased with the heating time from <1 to 33 microg/kg related to 3-6 min of frying time. The precision (RSD) was between 7 and 49% (HPTLC) and between 5 and 38% (HPLC) at these very low HAA levels formed.  相似文献   

20.
Species differences in the metabolism of acetylenic compounds commonly used in the formulation of pharmaceuticals and pesticides have not been investigated. To better understand the in vivo reactivity of this bond, the metabolism of propargyl alcohol (PA), 2-propyn-1-ol, was examined in rats and mice. An earlier study (Banijamali, A. R.; Xu, Y.; Strunk, R. J.; Gay, M. H.; Ellis, M. C.; Putterman, G. J. J. Agric. Food Chem. 1999, 47, 1717-1729) in rats revealed that PA undergoes extensive metabolism primarily via glutathione conjugation. The current research describes the metabolism of PA in CD-1 mice and compares results for the mice to those obtained for rats. [1,2,3-(13)C;2,3-(14)C]PA was administered orally to the mice. Approximately 60% of the dose was excreted in urine by 96 h. Metabolites were identified, directly, in whole urine by 1- and 2-D (13)C NMR and HPLC/MS and by comparison with the available reference compounds. The proposed metabolic pathway involves glucuronide conjugation of PA to form 2-propyn-1-ol-glucuronide as well as oxidation of PA to the proposed intermediate 2-propynal. The aldehyde undergoes conjugation with glutathione followed by further metabolism to yield as final products 3,3-bis[(2-acetylamino-2-carboxyethyl)thio]-1-propanol, 3-[(2-acetylamino-2-carboxyethyl)thio]-3-[(2-amino-2-carboxyethyl)thi o]-1-propanol, 3,3-bis[(2-amino-2-carboxyethyl)thio]-1-propanol, 3-[(2-amino-2-carboxyethyl)thio]-2-propenoic acid, and 3-[(2-formylamino-2-carboxyethyl)thio]-2-propenoic acid. A small portion of 2-propynal is also oxidized to result in the excretion of 2-propynoic acid. On the basis of urinary metabolite data, qualitative and quantitative differences are noted between rats and mice in the formation of the glucuronide conjugate of PA and in the formation of 2-propynoic acid and metabolites derived from glutathione. These metabolites represent further variation on glutathione metabolism following its addition to the carbon-carbon triple bond compared to those described for the rat.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号