Acetyl cholinesterase

Michaelis-Menten kinetics. Consider the hydrolysis of phenyl acetate catalyzed by acetyl cholinesterase,... 

Many pesticides are neurotoxicants poisoning the nervous system. A number of pesticides are acetyl cholinesterase inhibitors (Serat and Mengle 1973). Generally, pesticides determination has been performed by GC since the 1960 s (Morrison and Durham 1971 Fournier et al. 1978). There are no reference materials for pesticides in urine or serum, although as with PAHs there are a number biological matrices certified for the content of various pesticides available for environmental food and agriculture analysis and which may have some application in clinical chemistry. 

K.C. Gulla, M.D. Gouda, M.S. Thakur, and N.G. Karanth, Reactivation of immobilized acetyl cholinesterase in an amperometric biosensor for organophosphorus pesticide. Biochim. Biophys. Acta... 

The effect of Li+ upon the synthesis and release of acetylcholine in the brain is equivocal Li+ is reported to both inhibit and stimulate the synthesis of acetylcholine (reviewed by Wood et al. [162]). Li+ appears to have no effect on acetyl cholinesterase, the enzyme which catalyzes the hydrolysis of acetylcholine [163]. It has also been observed that the number of acetylcholine receptors in skeletal muscle is decreased by Li+ [164]. In the erythrocytes of patients on Li+, the concentration of choline is at least 10-fold higher than normal and the transport of choline is reduced [165] the effect of Li+ on choline transport in other cells is not known. A Li+-induced inhibition of either choline transport and/or the synthesis of acetylcholine could be responsible for the observed accumulation of choline in erythrocytes. This choline is probably derived from membrane phosphatidylcholine which is reportedly decreased in patients on Li+ [166],... 

Dose-effect dependence is shared by many OPC in both the acute and chronic tests. The higher dose of an anti-cholinesterase substance, the higher degree of both acetyl cholinesterase (AChE) inhibition in neural tissue and intoxication evidence. 

The UK Pesticide Safety Directorate (PSD) has decided to use the TEF approach for assessment of combined risk from exposure to mixtures of acetyl cholinesterase inhibitors (organophosphate (OP) compounds and carbamates) (PSD 1999). Despite clear differences in the action of carbamates and OP compounds, the index compounds selected for all acetyl cholinesterase inhibitors were either aldicarb (carbamate) or chlorpyrifos (OP). The POD for determining relative potency was predetermined as the dose level that produced 20% inhibition of red blood cell cholinesterase in a 90-day dietary study in rats. 

Acetyl cholinesterase activity AChE,. brain Neurotoxic parameter Organophosphate and carbamate pesticides Brain tissue 13-15... 

Acetyl cholinesterase activity AChE Ellman et al. (1961) Sturm et al. (1999)... 

Acetyl cholinesterase activity AChE, lab 6 muscle Bocquene et al. (1990)... 

In addition to battlefield trauma, there is also the risk of exposure to chemical weapons such as the nerve agents, notably the organophosphorus gases (soman, sarin, VX, tabun) [6]. Organophosphorus toxicity arises largely from their ability to irreversibly inhibit acetyl-cholinesterases, leading to effects associated with peripheral acetyl-choline accumulation (muscarinic syndrome) such as meiosis, profuse sweating, bradychardia, bronchioconstriction, hypotension, and diarrhoea. Central nervous system effects include anxiety, restlessness, confusion, ataxia, tremors. 

Methods for Determining Biomarkers of Exposure and Effect. Section 2.6.1 reported on biomarkers used to identify or quantify exposure to diazinon. Some methods for the detection of the parent compound in biological samples were described above. The parent chemical is quickly metabolized so the determination of metabolites can also serve as biomarkers of exposure. The most specific biomarkers will be those metabolites related to 2-isopropyl-6-methyl-4-hydroxypyrimidine. A method for this compound and 2-(r-hydroxy-l -methyl)-ethyl-6-methyl-4-hydroxypyrimidine in dog urine has been described by Lawrence and Iverson (1975) with reported sensitivities in the sub-ppm range. Other metabolites most commonly detected are 0,0-diethylphosphate and 0,0-diethylphosphorothioate, although these compounds are not specific for diazinon as they also arise from other diethylphosphates and phosphorothioates (Drevenkar et al. 1993 Kudzin et al. 1991 Mount 1984 Reid and Watts 1981 Vasilic et al. 1993). Another less specific marker of exposure is erythrocyte acetyl cholinesterase, an enzyme inhibited by insecticidal organophosphorus compounds (see Chapter 2). Methods for the diazinon-specific hydroxypyrimidines should be updated and validated for human samples. Rapid, simple, and specific methods should be sought to make assays readily available to the clinician. Studies that relate the exposure concentration of diazinon to the concentrations of these specific biomarkers in blood or urine would provide a basis for the interpretation of such biomarker data. 

Suvanine (358), an acetyl cholinesterase inhibitor was first isolated from species of Ircinia [316] and then later from a Coscinoderma species from Fiji and Palau when the structure was revised [317]. 

These compounds act as inhibitors in acetyl-cholinesterase metabolism5-113115 and are absorbed via inhalation, mouth, skin or muscous membranes of the eye. For Sarin, the LDI00 value for humans is expected to be 0.04-0.06 mg 1 kg-57... 

H. Schulze, E. Scherbaum, M. Anastassiades, S. Vorlova, R.D. Schmid and T.T. Bachmann, Development, validation, and application of an acetyl-cholinesterase-biosensor test for the direct detection of insecticide residues in infant food, Biosens. Bioelectron., 17 (2002) 1095-1105. 

Anthelmintic drugs can act in a variety of ways, by influencing the metabolism of the parasite (e.g. dismption of glucose and glycogen metabolism) or neuromuscular effects (e.g. inhibition of acetyl cholinesterase - organo-phosphates). The compounds are usually administered to animals orally, by injections, as feed additives or in the form of pour-on preparations. 

This system is also used for detection of supertoxins and chemical war gases based on organophosphorous compounds, responsible for the blocking of acetyl cholinesterase in the central nerve system. The system of enzymatic reactions used for the brief analysis of such substances is the following [4] ... 

Mixed model with concentration addition for all compounds that share 1 mode of action In current practice (e.g., Traas et al. 2002 Mulder et al. 2004 De Zwart and Posthuma 2005), concentration addition is also applied to mixtures of nonnarcotic compounds with the same mode of action, such as photosynthesis inhibition or acetyl-cholinesterase inhibition. The protocol is shown in Figure 5.2. 

Improvements in medication by use of acetyl cholinesterase inhibitors and general therapy significantly reduce symptoms at the onset of the disease [3, 4] but do not address the severe mortality in the final stages. A causal therapy is, therefore, still very much in demand, because no existing therapy effectively stops or even cures the disease. Identification of gene mutations linked to Alzheimer s disease-afflicted families in London and Sweden and additional polymorphisms that either cause or promote Alzheimer s disease have provided some insight into the biological pathways and the involvement of the amyloid precursor protein (APP) [5-8],... 

Lyophilized electric eel acetyl cholinesterase (C-3389, EC 3.1.1.7) was purchased from Sigma Chemical Company and stored below 0°C. 

Acetyl cholinesterase (from electric eel) Esterase, acetyl choline (9) (9000-81-1)... 

By disrupting the biological function of the enzyme acetylcholinesterase, insecticides such as aldicarb, parathion and methamidophos (WHO la) prevent neurotransmitter molecules from being broken down, causing them to accumulate In the spaces between nerve cells. In this way acetyl-cholinesterase inhibitors effectively jam the transmission of nervous signals between nerve cells. 

Carvalho, I., Miller, J. (1995) Synthesis of l-methyl-2-hydroxyiminomethyl-aryl-pyridinium salts with potential as acetyl-cholinesterase reactivators. Heterocycl. Commun. 1 403-10. 

H-4) Nerve gas. It is not necessary to cripple the Main Powerhouse in order to poison someone. Nerve gas, as well as organophosphate insecticides, inhibit acetyl cholinesterase (AOiE), an enzyme important in the degradation of acetylcholine to choline. This can cause paralysis through inhibiting AChE at the junction between... 

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