Isomerization and Beckmann rearrangement reactions in the metabolism of methomyl in rats     

Kurt Huhtanen  H.Wyman Dorough 《Pesticide biochemistry and physiology》1976,6(6):571-583

Methomyl {S-methyl-N-[(methylcarbamoyl)oxy]thioacetimidate}, also known as Lannate, may exist in two geometric configurations but the more stable syn isomer is the form applied as an insecticide. In the rat, syn[¹⁴CN]methomyl [CH₃S(CH₃)CNOC(O)NHCH₃] was metabolized to respiratory ¹⁴CO₂ and $\text{CH}{}_3{}^{14}\text{CN}$ in a ratio of about 2 to 1. Studies with the anti isomer showed that it was metabolized predominately to $\text{CH}{}_3{}^{14}\text{CN}$. These and other data are presented supporting the contention that syn methomyl is partially isomerized to the anti isomer in the animal prior to the hydrolysis of the ester linkage. After hydrolysis, the syn oxime [CH₃S(CH₃)¹⁴CNOH] is further metabolized to ¹⁴CO₂ while the anti oxime is metabolized to $\text{CH}{}_3{}^{14}\text{CN}$. Proposed immediate precursors to the carbon dioxide and acetonitrile, formed by Beckmann rearrangement of the syn and anti oximes, are CH₃S¹⁴C(O)NHCH₃ and $\text{[}\text{CH}{}_3{}^{\mathrm{14\oplus }}\text{CNSCH}{}_3\text{]x}{}^{\mathrm{?}}$, respectively.  相似文献   

Mechanism of inhibition reaction of acetylcholinesterase by phenyl N-methylcarbamates: Separation of hydrophobic,electronic, hydrogen bonding and proximity effects of aromatic substituents     

Takaaki Nishioka  Toshio Fujita  Katsuzo Kamoshita  Minoru Nakajima 《Pesticide biochemistry and physiology》1977,7(2):107-121

The association equilibrium constant, $\text{1}\text{K}{}_{\mathrm{d}}$, and the carbamylation constant, k₂, of 53 o-, m-, and p-substituted phenyl N-methylcarbamates with bovine erythrocyte acetylcholinesterase were determined. The $\text{1}\text{K}{}_{\mathrm{d}}$ value varied 1000-fold, whereas the k₂ value did not depend upon the nature and position of substituents. The variation in $\text{log}\text{(}\text{1}\text{K}{}_{\mathrm{d}}\text{)}$ was analyzed using free energy related substituent parameters and regression analyses. The effect of substituents at o-, m-, and p-positions was nicely separated into hydrophobic, electronic, hydrogen bonding, and proximity (steric and field electronic for o-substituents) factors. The physicochemical significance of these factors was established by comparison with those for model organic reactivities. The mechanism of the whole reaction process was elucidated in terms of physical organic chemistry.  相似文献   

Deuterium isotope effects on the formation of mercapturic acids from lindane in rats     

Norio Kurihara  Tetsuya Suzuki  Minoru Nakajima 《Pesticide biochemistry and physiology》1980,14(1):41-49

Metabolism experiments with rats showed that significant isotope effects ($\text{k}{}_{\mathrm{<mtext>H</mtext>}}\text{k}{}_{\mathrm{<mtext>D</mtext>}}\text{= 2.4}\text{to}\text{3.5}$) were associated with the in vivo formation of dichloro and trichlorophenylmercapturic acids from a 1:1 mixture of normal and hexadeuterated lindane. This is evidence that rate-determining dehydrogenation and dehydrochlorination, both of which proceed with significant isotope effects, are essential in the pathway of dichloro- and trichlorophenylmercapturic acid formation from lindane. No significant primary isotope effects were associated ($\text{k}{}_{\mathrm{<mtext>H</mtext>}}\text{k}{}_{\mathrm{<mtext>D</mtext>}}\text{= 1.31 ± 0.17}$) with the formation of monochlorophenylmercapturic acid. This suggests that the 1,2-dechlorination to tetrachlorocyclohexene followed by glutathione conjugation is the probable pathway that produces this metabolite from lindane.  相似文献   

Interaction of insecticides with the Ca²⁺-pump activity of sarcoplasmic reticulum     

M.C. Antunes-Madeira  Vitor M.C. Madeira 《Pesticide biochemistry and physiology》1982,17(2):185-190

The organophosphorus insecticides, parathion and azinphos (10^?5-10^?4M), significantly stimulate the Ca²⁺-pump activity of sarcoplasmic reticulum, while malathion has a limited effect. The rates of Ca²⁺ translocation and ATP hydrolysis are both stimulated and, apparently, the $\text{Ca}{}^{\mathrm{2+}}\text{ATP}$ ratio is improved. Parathion and azinphos maximally increase this ratio by 26 and 14%, respectively. The organochlorine compounds, DDT and aldrin, also stimulate the Ca²⁺ pump, and lindane has a reduced effect. These effects are smaller than those observed for parathion and azinphos. The order of effectiveness is similar to the toxicity of the compounds to mammals and can be described as follows: parathion > azinphos > DDT ≈ aldrin > malathion ≈ lindane.  相似文献   

Picrotoxinin receptor in the central nervous system of the American cockroach: Its role in the action of cyclodiene-type insecticides     

Keiji Tanaka  Jeffrey G. Scott  Fumio Matsumura 《Pesticide biochemistry and physiology》1984,22(1):117-127

The nature of the picrotoxinin receptor was studied using the central nervous system (CNS) of the American cockroach. It first was confirmed by using an electrophysiological technique that the abdominal nerve cord of the American cockroach was sensitive to picrotoxinin. By using a $\text{[}{}^3\text{H]α-dihydropicrotoxinin}$ binding test it was determined that the picrotoxinin receptor in CNS of this insect had a higher affinity toward picrotoxinin and heptachlor epoxide than the corresponding receptor in the rat brain. Also, the cockroach brain preparation had a higher percentage of specific binding in the total binding, making this material suitable for receptor studies. By using a sucrose density centrifugation technique, it was determined that the fraction sedimented at the interphase of 1.0 to 1.2 M sucrose at 100,000g contained the highest level of specific binding site. The receptor showed a sensitivity to all insecticidal cyclodienes tested, namely photodieldrin, oxychlordane, endrin, heptachlor epoxide, γ-chlordane, dieldrin, aldrin, heptachlor, and isodrin (expressed in the order of potency). Among four BHC isomers, the γ-isomer showed the highest potency to bind with this receptor.  相似文献   

Selective alterations of membrane properties of cultured human liver cells caused by the insecticide DDT     

K. Buff  A. Bründl 《Pesticide biochemistry and physiology》1984,22(1):36-42

A variety of membrane-specific parameters was examined in both intact cells and isolated plasma membranes following exposure of cultured human liver cells to the insecticide 1,1-(2,2,2-trichloroethylidene)bis(4-chloro)benzene (DDT). Uptake of DDT was at equilibrium within 6 hr. In contrast, a decrease in the number of β-adrenergic hormone receptors first became significant after 48 hr of cell exposure. Whereas the uptake was largely reversible, the loss in the number of β receptors did not recover after DDT-exposed cells were cultured in fresh medium lacking the insecticide. Experiments in vitro substantiated the time lag of the biological effect. The decrease in receptor proteins was persistent in membranes with increased phospholipid unsaturation. Temperature-activity profiles (“Arrhenius plots”) of $\text{Na}{}^{\mathrm{+}}\text{K}{}^{\mathrm{+}}\text{-ATPase}$ and 5′-nucleotidase were unchanged. Endogenous tryptophan fluorescence of membrane proteins was lower in membranes from DDT-exposed cells. These selective alterations in membrane parameters suggest a specific interaction of DDT with membrane proteins; interference with cellular protein synthesis is possible. The results indicate that membrane lipid “fluidization” does not play a physiologically important role in the mechanism of DDT action in biomembranes.  相似文献   

Cytochrome P-450 content and aldrin epoxidation to dieldrin in isolated rat hepatocytes     

Norio Kurihara  Nobuaki Hori  Reiji Ichinose 《Pesticide biochemistry and physiology》1984,21(1):63-73

A rat hepatocyte suspension effectively epoxidized aldrin to dieldrin with a V_max of 7.19 mol/mol P-450/min and a K_m of 9.27 μM. Viability and metabolic activity were stable for 6 hr after isolation when cells were maintained at room temperature (20°C) with the gentle introduction of $\text{O}{}_2\text{CO}{}_2$ onto the surface of the suspension. The cytochrome P-450 content of the suspension was 303 pmol/10⁶ cells. Primary maintenance culture of the cells also epoxidized aldrin. During culture for 3 days, metabolic activity decreased slowly day by day. Metabolic activity of microsomal fraction from rat liver was also examined. Microsomes epoxidized aldrin with a V_max of 5.11 mol/mol P-450/min and a K_m of 1.64 μM. Significant loss of some subspecies of cytochrome P-450 during fractionation of liver homogenate was indicated.  相似文献   

Induction of glutathione S-transferase by phenobarbital and pesticides in various house fly strains and its effect on toxicity     

T. Hayaoka  W.C. Dauterman 《Pesticide biochemistry and physiology》1982,17(2):113-119

The effect of phenobarbital and certain pesticides on glutathione S-transferase activity was investigated. The maximum amount of enzyme induction occurred 96 hr after phenobarbital treatment. Chlorinated hydrocarbons were more effective inducers than the other pesticides evaluated. Phenobarbital treatment did not alter the apparent K_m value but altered the $\text{V}{}_{\mathrm{<mtext>max</mtext>}}$ value of glutathione S-transferase to 3,4-dichloronitrobenzene. The amount of reduced glutathione was not increased by phenobarbital treatment. Pretreatment of house flies with phenobarbital provides some protection against methyl parathion, methyl paraoxon, azinphosmethyl, and methidathion toxicity.  相似文献   

The metabolism of p,p′-DDT by the feral pigeon (Columba livia)     

M.S. Sidra  C.H. Walker 《Pesticide biochemistry and physiology》1980,14(1):62-71

Male feral pigeons were dosed with ring-labeled $\text{[}{}^{14}\text{C}\text{]p,p′-}\text{DDT}$ and the tissues and droppings analyzed for total ¹⁴C, extractable ¹⁴C, and metabolites. Only 16% of an intraperitoneal dose of 1.5–2.2 mg kg^?1 was voided in the droppings over 28 days; the rate of loss reached a maximum on the 14th day and then fell quickly away. The rate of removal of ¹⁴C in droppings was low in comparison to that found in the rat and the Japanese quail. When pigeons were dosed with 32–38 mg kg^?1 DDT per bird, and killed after 77 days, 5.4% of the dose was eliminated in droppings and 87% was recovered in the body. The tissues and droppings from this experiment were analyzed for DDT and its metabolites. Of the ¹⁴C remaining in tissues 88% was accounted for as the apolar compounds DDE, DDT, and DDD. Approximately half of the ¹⁴C in droppings was present as DDE, DDT, and DDD, whereas 27–35% was apparently in conjugated form, extractable from aqueous solutions by ethyl acetate after prolonged acid hydrolysis. Two polar metabolites were isolated from the acid-released material. One was p,p′-DDA; the other was extractable from aqueous solution at pH 8 and was tentatively identified as a monohydroxy derivative of p,p′-DDT. DDE accounted for 93% of the ¹⁴C present as metabolites in tissues and droppings, clearly indicating the importance of this intermediate in this study. The metabolism of DDT in the feral pigeon is discussed in relation to its metabolism by other species.  相似文献   

Steric,electronic, and polar parameters that affect the toxic actions of O-alkyl,O-phenyl phosphonothionate insecticides     

Robert L. Metcalf  Robert A. Metcalf 《Pesticide biochemistry and physiology》1984,22(2):169-177

The toxic action of a series of O-alkyl, O-substituted-phenyl alkyl- and aryl-phosphonates and phosphonothionates have been evaluated by correlating the linear free energy parameters for steric (E_s), electronic (σ), and polar ($\text{σ}{}^1$) effects with topical LD₅₀ to the house fly and oral LD₅₀ to the white mouse. In molecules free from major steric interactions with the reactive P atom, variations in these linear free energy parameters account for >90% of the variations in the LD₅₀ values, and the degree of correlation with LD₅₀ is at least as precise as that with the biomolecular rate constants for inhibition of the target-site enzyme acetylcholinesterase. The value of correlations of linear free energy parameters with LD₅₀ in understanding quantitative structure-activity relationships is illustrated.  相似文献   

The mechanism of resistance to lindane and hexadeuterated lindane in the Third Yumenoshima strain of house fly     

Keiji Tanaka  Minoru Nakajima  Norio Kurihara 《Pesticide biochemistry and physiology》1981,16(2):149-157

The factors which cause lindane resistance in the Third Yumenoshima strain, a strain of house flies highly resistant to insecticides, were studied using hexadeuterated lindane. Hexadeuterated lindane has the same physicochemical properties as lindane, but the former is much less biodegradable than the latter. The LD₅₀ ratio of lindane to hexadeuterated lindane in this strain, deuterium isotope effect on LD₅₀ values, was larger than that in S_NAIDM, a susceptible (nonresistant) strain. The penetration rates of labeled and nonlabeled lindane through the insect cuticle were about the same for both strains. Thus, penetration rate does not cause resistance. The metabolic degradation of lindane in the resistant strain in vivo occurred much faster than in the susceptible strain. This was also the case for lindane degradation processes in vitro such as microsomal oxidation and glutathione conjugation. In both strains, significant isotope effects were observed in the degradation rates in vitro of labeled and nonlabeled lindane. Therefore, principal biodegradation and detoxication pathways should include reactions which cleave the CH bonds. When the much less biodegradable d₆ counterpart of lindane was applied to both strains, the susceptible strain became much more highly intoxicated than the other within 20 to 30 min. This indicates that a combination of both greater degradability and probably lower sensitivity at the action site are the main factors underlying resistance in the Third Yumenoshima strain.  相似文献   

The purification and characterization of esterases from insecticide-resistant and susceptible house flies     

L.R. Kao  N. Motoyama  W.C. Dauterman 《Pesticide biochemistry and physiology》1985,23(2):228-239

Four major esterases in one susceptible (CSMA) and two resistant (Hirokawa, E₁) house fly strains were separated by chromatofocusing. Of the four esterases, those with pI's of 5.1 and 5.3 accounted for 90% of the p-nitrophenyl butyrate hydrolyzing activity in the three house fly strains. They also accounted for 70% (Hirokawa, E₁) and 40% (CSMA) of the paraoxon-hydrolyzing activity as well as 87% (Hirokawa), 39% (E₁) and 66% (CSMA) of the malathion-hydrolyzing activity in microsomes as measured by esterase-antibody interaction. In the Hirokawa strain, the pI 5.1 esterase was the predominant esterase and was more active than that of the the CSMA strain. Different substrate specificities and a different K_m toward acetylthiocholine, as well as different rates of malathion and paraoxon hydrolysis between the Hirokawa and CSMA strains, suggest a qualitative difference in the pI 5.1 esterase. For the pI 5.1 esterase from the E₁ strain, a different substrate specificity, a different K_m for p-nitrophenyl butyrate, a different sensitivity to inhibitors, and a different rate of paraoxon hydrolysis suggest that it is a modified esterase. This esterase is not a phosphorotriester hydrolase, nor does it lack nonspecific esterase activity. It is a modified esterase which has a different substrate specificity when compared to the esterases from the other strains. The molecular weight of the esterases studied was approximately 220,000, with pH optima of about 7.0.The ratio of malathion α-monoacid to β-monoacid formation was about 9.0 for the pI 5.1 and 5.3 esterases and 1.5 for the pI 4.8 and 5.6 esterases. The existence of a higher $\text{α}\text{β}$ ratio for the pI 5.1 and 5.3 esterases and their significant rate of malathion hydrolysis in the Hirokawa strain indicate that an increase in the $\text{α}\text{β}$ ratio in house flies reported was due to the increase in the pI 5.1 esterase in the resistant strain.  相似文献   

抗性甜菜夜蛾Na-K-ATP酶、Ca-ATP酶和Ca-Mg-ATP酶对高效氯氟氰菊酯的敏感性   总被引：1，自引：1，他引：1  

伦才智  李艳伟  刘永杰  沈晋良  束怀瑞 《农药学学报》2006,8(4):335-338

分别测定了甜菜夜蛾Spodoptera exigua敏感和抗高效氯氟氰菊酯品系神经系统Na-K-ATP酶、Ca-ATP酶和Ca-Mg-ATP酶的活力。结果表明,敏感和抗性品系Na-K-ATP酶活力差异不显著,而抗性品系Ca-ATP酶和Ca-Mg-ATP酶活力明显低于敏感品系。在浓度为1.0×10-8~1.0×10-3 mol/L时,高效氯氟氰菊酯对敏感和抗性品系Na-K-ATP酶、Ca-ATP酶和Ca-Mg-ATP酶的活力均有抑制,并且对敏感品系的抑制作用高于对抗性品系。高效氯氟氰菊酯浓度为1.0×10-4 mol/L 时,对敏感品系Na-K-ATP酶活力的抑制率为29.6%,对抗性品系的为21.8%,对敏感品系Ca-ATP酶活力的抑制率为34.3%,对抗性品系为21.9%,对敏感品系Ca-Mg-ATP酶活力的抑制率为22.3%,对抗性品系为16.9%,存在显著差异。表明甜菜夜蛾抗性品系上述3种ATP酶对高效氯氟氰菊酯的敏感性已明显下降。  相似文献   

Studies on hydrolases in various house fly strains and their role in malathion resistance     

L.R. Kao  N. Motoyama  W.C. Dauterman 《Pesticide biochemistry and physiology》1984,22(1):86-92

Aliesterase, carboxylesterase, and phosphorotriester hydrolase activities in six house fly strains were studied in relation to malathion resistance. Selection of two susceptible strains with malathion for three generations resulted in an increase in both carboxylesterase activity and LD₅₀ of malathion, indicating that the increased detoxication by the enzyme was the major mechanism selected for malathion resistance. With the highly resistant strains, however, the carboxylesterase activity alone was not sufficient to explain the resistance level, and the involvement of additional mechanisms, including phosphorotriester hydrolase activity, was suggested. The E₁ strain, which had high phosphorotriester hydrolase activity but normal or low carboxylesterase activity, showed a moderate level, i.e., sevenfold resistance. Upon DEAE-cellulose chromatography, two or three esterase peaks were resolved from susceptible, moderately resistant, and highly resistant strains. The substrate specificity, the sensitivity to paraoxon inhibition, and the $\text{α}\text{β}$ ratio of malathion hydrolysis were studied for each esterase peak from the different strains. The results suggested the existence of multiple forms of esterases with overlapping substrate specificity in the house fly.  相似文献   

Studies on the chiral isomers of fonofos and fonofos oxon: I. Toxicity and antiesterase activities     

Philip W. Lee  Reza Allahyari  T.Roy Fukuto 《Pesticide biochemistry and physiology》1978,8(2):146-157

The toxicity of the (R)_P and (S)_P chiral isomers and racemates of fonofos and fonofos oxon to insects and white mice were determined. (R)_P-Fonofos and (S)_P-fonofos oxon were 2- to 12-fold more toxic to house flies, mosquito larvae, and mice than were the corresponding enantiomers. The racemates were intermediate in toxicity. Stereoselectivity also was observed in the in vitro inhibition of house fly-head and bovine erythrocyte acetylcholinesterase, horse serum cholinesterase, chymotrypsin, trypsin, and a variety of esterases. In all cases the (S)_P-oxon was a more potent inhibitor than the (R)_P-oxon with k₁ ratios of $\text{(S)}{}_{\mathrm{<mtext>P</mtext>}}\text{(R)}{}_{\mathrm{<mtext>P</mtext>}}$ ranging from 4- to 60-fold. Further, differences in levels of house fly-head, mouse brain, and blood cholinesterase obtained from house flies and mice treated with the enantiomers and racemates of fonofos and fonofos oxon were observed. Differences in toxicity of the enantiomers and racemates to house flies and mice were more closely related to in vivo than to in vitro cholinesterase inhibition.  相似文献   

Metabolism of lindane in house flies: Metabolic desaturation,dehydrogenation and dehydrochlorination,and conjugation with glutathione     

Keiji Tanaka  Norio Kurihara  Minoru Nakajima 《Pesticide biochemistry and physiology》1976,6(4):392-399

In lindane-treated house flies, a cis-dehydrogenated metabolite, $\text{(}\text{36}\text{45}\text{)-}\text{hexachlorocyclohexene}$, was identified by gas-liquid chromatography and mass spectrometry. The in vitro metabolism study showed that in the presence of NADPH the microsomal fraction of house flies converted lindane to three hexane-soluble metabolites. This conversion was inhibited by piperonyl butoxide, SKF-525A, and carbon monoxide. These metabolites were identified as $\text{(}\text{36}\text{45}\text{)-}\text{hexachlorocyclohexene}$, $\text{(}\text{36}\text{45}\text{)- and (}\text{346}\text{5}\text{)-pentachlorocyclohexene}$ (PCCHE) by gas-liquid chromatography. They, as well as lindane, were excellent substrates for the reaction with the postmicrosomal fraction in the presence of glutathione. While the reaction with lindane-d₆ showed a significant deuterium isotope effect (6.82), that of $\text{(}\text{36}\text{45}\text{)-}\text{PCCHE-d}{}_5$ did not (1.18). Enzymatic conjugation with glutathione probably occurs at the stage of PCCHE.  相似文献   

Oxidative cleavage of a carboxyester bond as a mechanism of resistance to malaoxon in houseflies     

W. Welling  A.W. de Vries  S. Voerman 《Pesticide biochemistry and physiology》1974,4(1):31-43

The synergistic effect of triphenyl phosphate (a carboxyesterase inhibitor), sesamex (inhibitor of microsomal oxidation) and O,O-diethyl O-phenyl phosphorothioate on the toxicity of malathion and malaoxon for one susceptible and two resistant strains of housefly was studies. It was found that in the resistant strain G (characterized by high carboxyesterase activity) both malathion and malaoxon were synergized by triphenyl phosphate, but only malaoxon (and not malathion) by sesamex. The other resistant strain E 1, moderately tolerant for malathion but highly resistant to malaoxon, differed from strain G in that triphenyl phosphate had no effect; its response to sesamex was similar to that of strain G. The third synergist, O,O-diethyl O-phenyl phosphorothioate, combined the properties of triphenyl phosphate and sesamex. It was found to be the best of the three compounds used.Biochemical in vitro studies showed that both resistant strains could degrade malaoxon oxidatively at a rate at least 10 × higher than that of the susceptible strain. This oxidation could be inhibited by very low concentrations of the thiono analogue; a malaoxon to malathion ratio of 10:1 gave an inhibition of about 70% at a malaoxon concentration of 5 × 10^?6M. The product of this oxidation is malaoxon β-monocarboxylic acid. This metabolite was also found 1 hr after application of malaoxon in vivo.The results mentioned in this paper indicate that houseflies may become resistant to malaoxon by an increased rate of oxidative carboxyester bond cleavage.  相似文献   

Mitochondrial changes during storage of untreated or CIPC-treated potatoes     

Patrick Ravanel  Michel Tissut 《Pesticide biochemistry and physiology》1984,22(1):1-7

During storage of potato tubers (Solanum tuberosum L., var. Bintje), important changes appear which affect respiratory control, $\text{ADP}\text{O}$, intensity of O₂ consumption in the presence of different substrates, and NAD⁺ dependence, In mitochondria extracted under strictly similar conditions, from patato tubers stored at 4°C, the respiratory control (RC) maintains a value near 4 for 4 to 5 months. It then declines progressively to low values. At 20°C, a stable RC of 4 can be observed for several months, which then decreases at the end of dormancy. Then, the RC increases sharply; at this stage, $\text{ADP}\text{O}$ are abnormally low, and, some time later, NAD⁺ dependence disappears. Mitochondria treated with 250 μM chlorpropham show a 50% inhibition of the electron transfer with exogenous NADH as substrate. After tuber treatment with 1% chlorpropham, sprouting is inhibited for several months. The activities of mitochondria extracted from such tubers remain unaffected by the treatment. The use of this phenylcarbamate for potato tuber treatment permits obtaining functional mitochondria from tubers after a slightly longer period of storage.  相似文献   

Inhibition of Penicillium duponti carboxylesterase by the fungicides captan and folpet     

Karl Neidert  Lee Van Epps  William Welch 《Pesticide biochemistry and physiology》1985,23(2):221-227

Captan, folpet, and perchloromethylmercaptan were effective inhibitors of Penicillium duponti p-nitrophenylpropionate esterase activity (I₅₀ = 0.5 – 2 μM) whereas α-naphthyl acetate esterase activity was not affected by the presence of these compounds. Captan and folpet are both equally effective at pH 7.3 and 8.3. The ionic composition of the medium had strong effects on the degree of inhibition produced by all inhibitors but did not alter esterase activity. Neither succinamide nor phthalimide caused inhibition of the p-nitrophenylpropionate esterase activity: The trichloromethylmercaptan portion of these fungicides appears to be responsible for the observed inhibition. The rapidity of captan and folpet inhibition of esterase activity (complete in < 1 min) compared to the rates of spontaneous decomposition ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{> 1}\text{min}$) and the insensitivity of captan and folpet inhibition to hydrogen ion concentration suggest that generation of spontaneous decomposition products is not required for inhibition. The results are consistent with a mechanism in which the entire fungicide molecule binds to the protein followed by enzyme-promoted reactions of captan and folpet which result in loss of esterase activity.  相似文献   

Importance of pH in assessing the potential for nitrosocarbamate formation in the stomach     

Robert W. Rickard  Gerd Walter-Echols  L.Jeffry Lawrence  H.Wyman Dorough 《Pesticide biochemistry and physiology》1982,18(3):325-333

Formation of the nitroso derivatives of ¹⁴C-labeled carbaryl, carbofuran, and p-chlorophenyl methylcarbamate (PCMC), and their subsequent stabilities were investigated using low levels of carbamate (0.5 μmol) and aqueous HCl concentrations encompassing those considered maximum for the gastric contents of humans (pH 1–2) and of rats (pH 3–4). Reacting the carbamates with excess sodium nitrite for 10 min at 37°C in a pH 1.0 HCl solution gave nitrosocarbamate yields of 42 to 64%, while only trace amounts were formed at pH 2 and above. The nitrosocarbamates were most stable at pH 3–5 with half-lives ranging from 114 to 470 min. Stability of all three nitroso derivatives was considerably less at pH 1.5 ($\text{t}\text{1}\text{2}$, 25–34 min), but at pH 7 the stability varied: nitroso-PCMC $\text{t}\text{1}\text{2}$, 6 min; nitrosocarbofuran $\text{t}\text{1}\text{2}$, 70 min; nitrosocarbaryl $\text{t}\text{1}\text{2}$, 139 min. Denitrosation to the parent carbamate was the predominant degradation pathway at pH 1.5, but at pH 3–7 degradation was primarily by hydrolysis of the carbamate ester linkage. Each of the nitrosocarbamates was directly mutagenic in the S. typhimurium assay system. Since the data show that nitrosation of residue levels of carbamate pesticides occurs readily at pH 1 but not at pH 2 and above, it is critical that gastric contents of any animal model used for assessing nitrosocarbamate formation have a pH approaching 1 as may occur in the human stomach.  相似文献