Cholinesterases types

A second advantage of the use of cholinesterase typing over that of... 

H9. Harris, H., and Robson, E. B., Screening tests for the atypical and intermediate serum-cholinesterase types. Lancet 2, 218-221 (1963). 

Hll. Harris, H., and Whittaker, M., Differential response of human serum cholinesterase types to an inhibitor in potato. Nature (London) 183, 1808-1809 (1959). 

L18. Lee, G., and Robinson, J. C., Agar diffusion test for serum cholinesterase typing and... 

Cholinesterases (ChEs), polymorphic carboxyles-terases of broad substrate specificity, terminate neurotransmission at cholinergic synapses and neuromuscular junctions (NMJs). Being sensitive to inhibition by organophosphate (OP) poisons, ChEs belong to the serine hydrolases (B type). ChEs share 65% amino acid sequence homology and have similar molecular forms and active centre structures [1]. Substrate and inhibitor specificities classify ChEs into two subtypes ... 

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

Cholinesterases are another group of B-esterases. The two main types are acetylcholinesterase (EC 3.1.1.7) and unspecific or butyrylcholinesterase (EC 3.1.1.8). Acetylcholinesterase (AChE) is found in the postsynaptic membrane of cholinergic... 

Before discussing the structure of the neurotoxins, it is necessary to define the types of neurotoxins. Three types of neurotoxins have been found so far in snake venoms. The first one is a postsynaptic neurotoxin, the second is a presynaptic neurotoxin, and the last is a cholinesterase inhibiting neurotoxin. Most sea snake venoms seem to contain only the postsynaptic neurotoxin. Only in Enhydrina... 

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

There are different types of cholinesterases in the human body, and they differ in their location in tissues, substrate affinity, and physiological function. The main ones are ACHE, present in nervous tissue and red blood cells (RBC-ACHE), and plasma cholinesterases (PCHE), present in glial cells, plasma, and liver. The physiological functions of RBC-ACHE and PCHE, if any, are unknown. 

L The answer is b. (Hardman, pp 166-167.) Echothiophate iodide is a long-acting (irreversible) cholinesterase inhibitor. It is used topically in the eye for the treatment of various types of glaucoma. Maximum reduction of intraocular pressure occurs within 24 h, and the effect may persist for several days. The drug is a water-soluble compound, which affords it a practical advantage over the lip id-soluble isofluorphate (another cholinesterase inhibitor used to treat glaucoma). 

The answer is d. (Hardman, p T36J The addition of a vasoconstrictor, such as epinephrine or phenylephrine, to certain short-acting, local anesthetics is a common practice in order to prevent the rapid systemic absorption of the local anesthetics, to prolong the local action, and to decrease the potential systemic reactions. Some local anesthetics cause vasodilation, which allows more compound to escape the tissue and enter the blood. Procaine is an ester-type local anesthetic with a short duration of action due to rather rapid biotransformation in the plasma by cholinesterases. The duration of action of the drug during infiltration anesthesia is greatly increased by the addition of epinephrine, which reduces the vasodilation caused by procaine. 

Thus a distinction was provided between simple esterases, such as fiver esterase, which catalysed the hydrolysis of simple aliphatic esters but were ineffective towards choline esters. The term 1 cholinesterase was extended to other enzymes, present in blood sera and erythrocytes of other animals, including man, and in nervous tissue, which catalysed the hydrolysis of acetylcholine. It was assumed that only one enzyme was involved until Alles and Hawes2 found that the enzyme present in human erythrocytes readily catalysed the hydrolysis of acetylcholine, but was inactive towards butyrylcholine. Human-serum enzyme, on the other hand, hydrolyses butyrylcholine more rapidly than acetylcholine. The erythrocyte enzyme is sometimes called true cholinesterase, whereas the serum enzyme is sometimes called pseudo-cholinesterase. Stedman,3 however, prefers the names a-cholinesterase for the enzyme more active towards acetylcholine, and / -cholinesterase for the one preferentially hydrolysing butyrylcholine. Enzymes of the first type play a fundamental part in acetylcholine metabolism in vivo. The function of the second type in vivo is obscure. Not everyone agrees with the designation suggested by Stedman. It must also be stressed that enzymes of one type from different species are not always identical in every respect.4 Furthermore,... 

It may be noted that many of the anticholinesterases of the competitive type are equally potent as inhibitors of a- and / -cholinesterases. We should add, however, that the existence of an anionic site in / -cholinesterases has been questioned.1... 

Science magazine had printed a summary of a pharmacology conference where a prominent scientist, Dr. David Nachmanson, had expounded his formulation of the mode of action of cholinesterase inhibitors. His list of references included a study published earlier by a Dr. VanSint. Fred and I sensed the opportunity to shake up our beloved Chief Scientist a little bit. We forged a dissenting view addressed from Van to Dr. Nachmanson, fdling it with preposterous assertions. We typed it carefully, and signed it Van M. Sim, M.D. (as distinct from Dr.VanSinf ). 

Khalid A, Zaheer-ul-Haq Anjum S, Khan MR, et al. Kinetics and structure-activity relationship studies on pregnane-type steroidal alkaloids that inhibit cholinesterases, BioorgMed Chem 12 1995—2003, 2004. 

Cholinesterase inhibitors are a very important class of compounds related to cholinomimetics. Besides their therapeutic importance, a few of them are used as pesticides in agriculture, and the most toxic are used as chemical poisoning agents. Use of these substances is based on changes that take place after inactivation of cholinesterase or pseudocholinesterase (a less specific enzyme), i.e. effects observed as a result of acetylcholine buildup in neuro-effector compounds. Cholinesterase inhibitors are classified both by their chemical structure as well as by the type of their chemical reaction with the enzyme, which determines their temporary action. 

Anesthesia Rivastigmine, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. 

The toxicology and pharmacology of esters of the type 126 have been studied in some detail, both because of their commercial importance and their close structural relationship to some nerve gases. They are poisonous compounds which act, like the related alkyl dithionophosphate esters, by cholinesterase inhibition, and their misuse has been associated with certain mental disorders. As a consequence of this pronounced biological activity, much attention has been directed to both the detection and isolation of the compounds as such, ... 

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