Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of enzymes, presumably secreted by larvae of B. microplus under natural feeding conditions, have been investigated in the skin of previously unexposed calves 4 h after infestation at the attachment site. Carboxylic ester hydrolase activity was demonstrated in the dermis, immediately adjacent to the mouthparts, or in the attachment cone, depending on substrate and reaction pH. The carboxylic ester hydrolase acting on naphthol AS-D acetate (2-acetoxy-3-naphthoic-O-toluidide) at pH 7-1 was characteristically found in the dermis and not in the attachment cone. The use of specific inhibitors showed that this enzyme was primarily a B-esterase or carboxylesterase with possibly a small portion of C-esterase or acetylesterase. It is postulated that carboxylic ester hydrolase could contribute to the dilation observed in the subepidermal capillaries adjacent to the attachment sites of unexposed animals, through the formation of plasma kinins. Other enzymes demonstrated in the dermis, adjacent to the mouthparts, were triacylglycerol lipase, as an aggregated deposit, and small amounts of aminopeptidase (microsomal) and monophenol monooxygenase. Aminopeptidase (microsomal) was also demonstrated in the attachment cone or adjacent epidermis, according to the substrate used. No activity was found in the host tissue, in association with the attachment site, for either alkaline or acid phosphatase, acetylcholinesterase or cholinesterase, peroxidase or amine oxidase (flavin-containing), despite the intense histochemical reaction for the latter in the tissues of larvae.
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PMID:Boophilus microplus: characterization of enzymes introduced into the host. 102 62

Carbaryl, a carbamate insecticide, exerts its toxic effect in animals by inhibiting the activity of neural acetylcholinesterase. Differences in sensitivity of this enzyme to inhibition were studied after intraperitoneal administration to chickens and rats. A dose of 900 mg/kg to chickens and 70 mg/kg to rats caused equivalent inhibition of brain cholinesterase activities (57% +/- 6 and 47% +/- 4, respectively) 60 min after administration, which was the time of maximal cholinergic signs. Signs of toxicity (salivation, respiratory distress, muscle tremors and weakness) were more pronounced in rats than in chickens when brain acetylcholinesterase was inhibited to the same extent in both species. Carboxylesterase activities in brain, liver, and plasma were also inhibited 60 min after administration of carbaryl to chickens and rats. Activities of enzymes associated with hepatic microsomes were unaffected. Specific activities of brain esterases, including acetylcholinesterase, carboxylesterase and neurotoxic esterase, were higher in untreated chickens than in untreated rats. Specific activities of liver esterases (carboxylesterase, A-esterase) were, however, 4- and 10-fold lower in untreated chickens than in untreated rats. Total clearance of carbaryl in the chicken, determined after intravenous administration of 5 mg/kg, was 0.26 +/- 0.02 l/kg/min. This value is 5.7 times higher than that reported for the rat, indicating that the relatively lower activities of esterases in the liver of chickens did not affect the clearance of this chemical in the avian species.
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PMID:Toxicity and toxicokinetics of carbaryl in chickens and rats: a comparative study. 150 71

Carboxylesterase (EC 3.1.1.1) has played an important part in our understanding of the toxicokinetic behaviour of the organophosphorus cholinesterase inhibitors. Carboxylesterases are a heterogeneous group of enzymes that can be separated on the basis of their isoelectric points and by their substrate-specificity. We have purified the isoenzyme (pI 5.8) present in greatest activity in rat lung to near homogeneity. The enzyme was purified by (NH4)2SO4 precipitation, gel filtration, chromatofocusing, separation on anion- and cation-exchangers and hydrophobic-interaction chromatography. The purified enzyme has a molecular mass of approx. 180 kDa with subunits of 60 kDa. The substrate and inhibitor specificities of the enzyme have been characterized. Edman degradation revealed the first 19 amino acid residues of the enzyme. The N-terminus was found to be tyrosine. Inhibition of the enzyme by organophosphorus compounds differed greatly from that of cholinesterases, despite the partial analogy at the N-terminal region.
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PMID:Purification and characterization of carboxylesterases from rat lung. 201 99

Rats injected with a nonlethal acute dose (100 micrograms/kg, sc) of soman (pinacolyl methylphosphonofluoridate) exhibited signs of anticholinesterase toxicity beginning at 5-15 min with increasing severity and lasting for 4-6 hr. Generalized tremors and seizure activity indicated comparatively greater involvement of the central cholinergic system than peripheral neuromuscular effects. During peak toxicity, all the brain regions tested showed more than 95% inhibition of acetylcholinesterase (AChE) activity. The cortex area was maximally affected (99% inhibition). Among skeletal muscles, soleus AChE was most severely affected (94%) and extensor digitorum longus (EDL) the least (72%). Inhibition of EDL AChE occurred at a much slower rate than in brain and other muscles. Significant recovery of AChE activity was seen by 48-72 hr after soman treatment in both brain and skeletal muscles. By Day 7, recovery was virtually complete in skeletal muscles but not in brain, although significant recovery had occurred by this time. Muscle fiber necrosis developed within 6 hr in the soleus and diaphragm, while no necrotic fibers were found in the EDL. The 16 S AChE molecular form showed the fastest recovery of the AChE isozymes in all three muscles. Full recovery was seen after 7 days in soleus and was increased to greater than control activity in diaphragm and EDL. The inhibition pattern of butyrylcholinesterase (BuChE) activity was similar to that described for AChE activity, but the recovery was comparatively faster. Carboxylesterase activity in plasma was decreased to less than 10% of control within 1 hr and recovered to 53% of control within 24 hr. No significant inhibition was seen in hepatic carboxylesterase activity. It can be concluded that soman-induced acute toxicity is directly related to the rate and degree of AChE inhibition. A significant amount of soman binds to non-AChE enzymes with serine sites such as BuChE and carboxylesterases.
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PMID:Biochemical and histochemical alterations following acute soman intoxication in the rat. 356 14

The trichothecene T-2 toxin was rapidly hydrolyzed by rat liver microsomal fraction into HT-2 toxin which was the main metabolite. The metabolism was completely blocked by paraoxon, a serine esterase inhibitor, but not affected by EDTA or 4-hydroxy mercury benzoate, inhibitors of arylesterase and esterases containing SH-group in active site, respectively. Among the serine esterases carboxylesterase (EC 3.1.1.1), but not cholinesterase (EC 3.1.1.8) hydrolysed T-2 toxin to HT-2 toxin. Carboxylesterase activity from liver microsomes was separated into at least five different isoenzymes by isoelectric focusing, and only the isoenzyme of pI 5.4 was able to hydrolyse T-2 toxin to HT-2 toxin. The toxicity of T-2 toxin in mice was enhanced by pre-treatment with tri-o-cresyl phosphate (TOCP), a specific carboxylesterase inhibitor. This confirms the importance of carboxylesterase in detoxification of trichothecenes.
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PMID:Metabolism of T-2 toxin by rat liver carboxylesterase. 370 11

Some enzymatic parameters of neuronal transmission as well as the occurrence and the properties or carboxylic ester hydrolases in the hippocampal region of the wistar rat are investigated by histochemical and comparable biochemical methods. The acetylcholinesterase-, the monoamine oxidase- and the GABA-transaminase reaction are found at fibre structures, the course of which is seen more or less clearly. The histochemical picture of these enzymes is very different in each hippocampal layer and mainly limited by the corresponding number of reacting fibres. The origin and attribution of the fibres to the afferent and efferent systems are discussed. The occurrence of the acetylcholinesterase, the monoamine oxidase and the GABA-transferase as well as of the biogenic amines and the GABA are hints for the existence of cholinergic as well as aminergic and GABA-ergic processes of transmission in the hippocampal region. In the hippocampal region, the cingular and the optic cortex carboxylic ester hydrolases acetylcholinesterase, unspecific cholinesterase and the A-, B- and C-esterase could be demonstrated. The acetylcholinesterase of the hippocampal region is for the most part firmly membrane-bound and exists at least in two multiple, formalin-sensitive forms which are histochemically located in fibre structures. The unspecific cholinesterase, localized in the hippocampal region within vessel and capillary walls, exists in an electrophoretic mobile, formalin-sensitive form. Nearly half of the enzymes is soluble. A preferred binding to definite cell organelles was not demonstrable. In the hippocampal region the 3 multiple forms of the A-esterase are formalin-instable lyoenzymes. Good solubility and high formalin-sensitivity are the reason, why A-esterases are not demonstrable with usually histochemical methods. In the hippo ampal region the B-esterase is tightly bound to n electrophoretic mobile formalin-sensitive form in the microsomal fraction. In the cytoplasm of the neurones the desmoenzyme appears more or less granular. The 3 multiple forms of the C-esterase are formalin-sensitive to a different degree. Good solubility and low formalin-sensitivity, compared to the A-esterases are responsible for the fact, that the C-esterases can be shown histochemically only after en-bloc-fixation. The reaction products are granular. The similar behaviour of C-esterase and acid phosphatase, stated by many tests, suggests the C-esterases of the B- and C-type results in the same reactivity of pyramidal and granular cells of the hippocampal region. Some small, very strongly reacting cells belong to other cell types (probably basket cells or polymorphic cells).
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PMID:[Histochemical and biochemical investigations of the hippocampus and neocortex of the Wistar rat. I. Carboxylic ester hydrolases, transmitter enzymes and transmitters of the normal animal (author's transl)]. 610 39

Carboxylesterase was obtained from human liver in an electrophoretically homogeneous form. The monomeric molecular weight of the enzyme was 60,000 and the enzyme associated to form trimers. Purified human liver carboxylesterase was compared with human serum carboxylesterase, purified earlier. Serum carboxylesterase hydrolyzed a typical cholinesterase substrate and aryl acylamide, whereas liver carboxylesterase did not hydrolyze these compounds. Both carboxylesterases catalyzed the hydrolysis of short-chain triacylglycerols, such as tributyrin, and medium-chain monoacylglycerols, such as monocaprin, but not the hydrolysis of long-chain triacylglycerols. Serum carboxylesterase activity was inhibited by p-trimethylammoniumanilinium dichloride and neostigmine, whereas liver carboxylesterase activity was not affected by these compounds. Liver and serum carboxylesterase activities were both strongly inhibited by phenylmethylsulfonyl fluoride.
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PMID:Human liver carboxylesterase. Properties and comparison with human serum carboxylesterase. 641 19

Carboxylesterase activity of primate brain (Macaca mulatta) was determined using phenyl valerate (PV) as substrate. Eight carboxylesterases of primate brain were characterized in respect to PV-hydrolysing activity and to their inhibition rate constants for the reaction with organophosphorus compounds. Carboxylesterase III was identified as neurotoxic esterase (NTE). Organophosphate inhibition data of primate acetylcholinesterase (EC 3.1.1.7) and of primate cholinesterase (EC 3.1.1.8) were determined and are compared to corresponding data of primate brain carboxylesterases. Physiological functions, clinical and toxicological significance of primate brain carboxylesterases are discussed.
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PMID:Carboxylesterases in primate brain: characterization of multiple forms. 661 50

A novel series of prostaglandin F2 alpha (PGF2 alpha) prodrugs, with acyl ester groups at the 9, 11, and 15 positions, was prepared in order to design clinically acceptable prostaglandins for treating glaucoma. Studies involving isolated esterases and ocular tissue homogenates indicated that 9-acyl esters cannot provide a prodrug since PGF2 alpha would not be formed as a product. In contrast, 11-mono, 15-mono, and 11, 15-diesters were converted to PGF2 alpha in ocular tissues and could, therefore, be considered as prodrugs of PGF2 alpha. Carboxylesterase (CE) appeared critically important for the hydrolytic conversion of those PGF2 alpha prodrugs where the 11 or 15-OH group was esterified and such prodrugs were not substrates for acetylcholinesterase (ACHE) or butyrylcholinesterase (BuCHE). The enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester was also investigated for comparative purposes. This PGF2 alpha prodrug was a good substrate for CE, but was also hydrolysed by BuCHE, albeit at a much slower rate. The most striking feature of the enzymatic hydrolysis of PGF2 alpha-1-isopropyl ester in ocular tissue homogenates was that it was much faster than for prodrugs esterified at the 11 and/or 15 positions. In terms of ocular hypotensive activity, all prodrugs which showed detectable conversion to nascent PGF2 alpha were potent ocular hypotensives. Although no separation of ocular hypotensive and ocular surface hyperaemic effects was apparent for PGF2 alpha-1-isopropyl ester, a temporal separation of these effects was apparent for the novel PGF2 alpha ester series. This difference may reflect an unfavourably rapid conversion of PGF2 alpha-1-isopropyl ester in ocular surface tissues compared with anterior segment tissues.
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PMID:Studies on a novel series of acyl ester prodrugs of prostaglandin F2 alpha. 791 69

Young rats are more sensitive than adults to a single oral dose of chlorpyrifos, an organophosphorus pesticide. A direct comparison of chlorpyrifos effects in young (postnatal day 17; PND17), adolescent (PND27), and adult (70 days) Long-Evans rats was conducted to determine quantitative and possibly qualitative differences in sensitivity in terms of behavioral changes and cholinesterase (ChE; total cholinesterase activity) inhibition at these three ages. Male and female rats were administered chlorpyrifos orally at one of two doses (PND17, 5 or 20 mg/kg; PND27, 20 or 50 mg/kg; adult, 20 or 80 mg/kg) and tested at either 3.5 or 6.5 h after dosing. Behavioral testing included observational evaluations and measurements of motor activity and was followed immediately by tissue collection for ChE determination in brain and blood. For both behavioral changes and ChE inhibition, peak effects occurred at 3.5 h in adult male and PND27 rats (both sexes) and at 6.5 h in adult female and PND17 rats (both sexes). Comparisons of the 20 mg/kg dose across ages showed generally less ChE inhibition and fewer behavioral effects with increasing age, except that the adult females were similar to the PND27 rats. The high dose used for each age group produced similar brain ChE inhibition (80-90%) and generally similar behavioral effects. Interestingly, a few end-points in the young rats were less affected than in adults at this level of ChE inhibition. The degree of ChE inhibition in the brain more closely paralleled the blood inhibition in the younger rats, compared to the adults. Carboxylesterase (CaE) and A-esterase are known to play an important role in the detoxification of organophosphates and may be partially responsible for these sensitivity differences. Liver and plasma CaE and A-esterase activities were measured in untreated male rats on PND1, 4, 7, 12, 17, and 21 and in adults of both sexes (82-92 days old). Preweanling rats had considerably less activity of both enzymes, and adult females had less liver CaE activity than males. These differences in detoxifying enzymes correlate with the age-related differences in behavioral and biochemical effects, as well as the gender differences seen in adult rats, and thus may be a major influence on the differential sensitivity to chlorpyrifos.
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PMID:Age- and gender-related differences in sensitivity to chlorpyrifos in the rat reflect developmental profiles of esterase activities. 1004 24


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