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Negative Feedback 2
Published in James E. Ferrell, Systems Biology of Cell Signaling, 2021
So far we have focused mainly on how signaling systems initiate a response. But how a system terminates a response is just as important, and cells have evolved numerous strategies to ensure that their responses are not too protracted. Sometimes a cell stops responding by getting rid of the stimulus. This is true in the case of acetylcholine, the neurotransmitter that mediates the contraction of skeletal muscle and the relaxation of smooth muscle in the peripheral nervous system and functions as a neuromodulator in the central nervous system. Cholinergic signals are terminated largely through the hydrolysis of acetylcholine by the enzyme acetylcholinesterase, and compounds that inhibit acetylcholinesterase are used in the treatment of Alzheimer’s disease and for killing insects. The effects of the neurotransmitters dopamine, serotonin, and norepinephrine are limited by degradation too, and drugs that inhibit one of the degrading enzymes, monoamine oxidase, are used to treat depression. These neurotransmitters are also pumped back into the neuron that released them, and this reuptake plays a role in terminating their action. The most commonly prescribed antidepressants inhibit one or more of these reuptake pumps, and so does cocaine.
Basic Chemical Hazards to Human Health and Safety — II
Published in Jack Daugherty, Assessment of Chemical Exposures, 2020
Acetylcholine is an important neurotransmitter and the inhibition of choline by substances such as organophosphates (see Chapter 3) prevents the firing of adjacent neurons. The release of acetylcholine into the synapse fires the receiving neuron. Normally, the acetylcholine is rapidly degraded and the receiving neuron restores itself and awaits a new signal to fire. If the acetylcholine is not broken down rapidly enough, the receiving neuron keeps firing and symptoms such as muscle incoordination, nausea, and dizziness, which lead to seizures and unconsciousness, are observed. The serine enzyme acetylcholinesterase provides for the expedient breakdown of acetylcholine. Organophosphate molecules enter at the enzyme’s active site and a proton donation binds the serine to the phosphate. Symptoms of the inhibition result from acetylcholinesterase being about 60–70 percent phosphorylated. Subsequently, an excess of acetylcholine creates overstimulation at synapses between nerves and voluntary muscles in the CNS and in the parasympathetic branch of the ANS. In human patients, this inhibition means constriction of the pupil, slowing of heart rate, excessive salivation, and muscle contraction. Death by asphyxiation because the diaphragm and related breathing muscles fail to function properly, or because the respiratory center in the brain malfunctions, is the ultimate symptom of this situation.
Use of Physiological and Biochemical Measures in Pollution Biology
Published in Alan G. Heath, Water Pollution and Fish Physiology, 2018
Acetylcholinesterase (AChE) is found in nearly all tissues. Because this enzyme is associated with neuronal synapses, the concentration is proportional to the extent of innervation of the tissue (Rao and Rao, 1984). AChE is inhibited by organophosphorus and carbamate insecticides, and the extent of this inhibition has been used to diagnose fish that are suffering from this type of poisoning (Zinkl et al., 1991). While inhibition of this enzyme is considered a classical example of a biomarker specific for a particular group of toxicants, in vitro studies implicate several metals as possible inhibitors as well (Olson and Christensen, 1980). Shaw and Panigraphi (1990) found inhibition of AChE in fish from a mercury-contaminated estuary, and the degree of inhibition was proportional to the mercury body burden. These findings suggest caution in interpreting AChE declines as being exclusively due to pesticide contamination.
Characterization of the antioxidant activity, total phenolic content, enzyme inhibition, and anticancer properties of Achillea millefolium L. (yarrow)
Published in Instrumentation Science & Technology, 2022
Nagihan Karaaslan Ayhan, Merve Goksin Karaaslan Tunc, Samir Abbas Ali Noma, Ali Kurucay, Burhan Ates
Acetylcholinesterase (AChE, E.C.3.1.1.7) is a key cholinesterase that plays an important role in cholinergic transmission. Enzymes are expressed in all tissue cells but have less activity. Acetylcholinesterase enzyme is primarily in muscles, brain, and cholinergic neurons and is responsible for the rapid hydrolysis of acetylcholine (ACh) at synapses.[24] Indeed, in the late phase of Alzheimer’s disease (AD), AChE levels increase significantly. Cholinesterase inhibitors or anti-cholinesterase prevent the breakdown of the neurotransmitter butyrylcholine or acetylcholine. The cholinergic system, which plays a significant role in the regulation of cognition, learning, and memory processes, has been extensively studied for the design of Alzheimer’s disease drugs.[25]
Acute toxicity evaluation of triazophos, deltamethrin and their combination on earthworm, Eudrilus eugeniae and its impact on AChE activity
Published in Chemistry and Ecology, 2019
Shikha Singh, Rishikesh K. Tiwari, Ravi S. Pandey
A wide range of biomarkers have been developed in earthworm like behavioural, enzymological, histopathological and neurological for studying the effect of both organic and inorganic substances [13]. Among these biomarkers, behavioural and enzymological/neurological aspects are explored in this study. Acetylcholinesterase (AChE; EC 3.1.1.7) is a key biomarker enzyme in the nervous system, terminating the impulses by catalysing the hydrolysis of acetylcholine into acetate and choline. It is considered as target site of inhibition by organophosphate and carbamate pesticide, particularly organophosphorus which inhibits the enzyme activity by covalently phosphorylating the serine residue within active site group. The irreversible inhibition of AChE results in the excess accumulation of acetylcholine causing hyperactivity and consequently impairment of neuronal and muscular system. However, pyrethroid (deltamethrin) blocks sodium channels and affects the function of GABA-receptors of nerve filaments resulting into the inhibition of AChE activity [14,15].
Effects of chronic exposure to sediments from the Zarzis area, Gulf of Gabes, measured in the mussel (Mytilus spp.): a multi-biomarker approach involving oxidative stress and neurotoxicity
Published in Soil and Sediment Contamination: An International Journal, 2020
Rayda Ghribi, Alberto Teodorico Correia, Boubaker Elleuch, Bruno Nunes
Acetylcholinesterase (AChE) plays an important role in neurotransmission in both invertebrates and vertebrates, being responsible for the hydrolysis of acetylcholine into choline and acetic acid at the cholinergic synapses and neuromuscular junctions (Peña-Llopis, Ferrando, and Peña 2003). It is an enzyme involved in the regulation of nerve impulse and its inhibition is an established biomarker of neurotoxicity of organophosphate and carbamate pesticide effects (Fulton and Key 2001). Recent studies suggest that it may also indicate general chemical toxicity (Tsangaris et al. 2010) which lead to its wide use as a biomarker for the diagnosis of other types of pollutants such as metals and PAHs (Akila et al. 2018; Grintzalis, Georgiou, and Dailianis 2012; Tsangaris et al. 2010)