Cholinesterases mutated

Earlier work in this field [28] indicated that acetylcholinesterase enzymes would be suitable biomolecules for the purpose of pesticide detection, however, it was found that the sensitivity of the method varied with the type and source of cholinesterase used. Therefore the initial thrust of this work was the development of a range of enzymes via selective mutations of the Drosophila melanogaster acetylcholinesterase Dm. AChE. For example mutations of the (Dm. AChE) were made by site-directed mutagenesis expressed within baculovirus [29]. The acetylcholinesterases were then purified by affinity chromatography [30]. Different strategies were used to obtain these mutants, namely (i) substitution of amino acids at positions found mutated in AChE from insects resistant to insecticide, (ii) mutations of amino acids at positions suggested by 3-D structural analysis of the active site,... 

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],... 

A polymorphism in serum cholinesterase is one of the oldest polymorphisms known. It leads to prolonged muscle relation or prolonged paralysis after administration of the muscle relaxant succinylcholine. Several mutants occur, the most common is a point mutation causing the substitution of glycine for aspartic acid at position 70. This variant shows defective binding of choline esters to the anionic binding site but has normal activity with neutral or positively charged esters. There also numerous other variants, many with partial or complete loss of activity. 

SAFETY PROFILE Poison by ingestion, skin contact, intraperitoneal, subcutaneous, and intravenous routes. Human systemic effects by skin contact unspecified blood system effects. Mutation data reported. A cholinesterase inhibitor. An insecticide. See also PARATHION. When heated to decomposition it emits very toxic fumes of cr and POx. 

Broomfield, C.A., Millard, C.B., Lockridge, O., and Caviston, T.L. 1995, Mutations of human hutyrylchohnesterase glycine 117 to histidine preserves activity hut confers resistance to organophosphorus inhihi-tors, in Enzymes of the Cholinesterase Family, D.M. Quinn et al., eds.. Plenum Press, New York, p. 169. 

A special problem is the certain identification of silent gene cases (EjE)). There are obviously several different point mutations that may render cholinesterase virtually inactive, but the distinction between these types at the present time would be entirely a matter of research. The immediate problem is always to establish whether a given person s lack of... 

There appear to be several, if not many, possible mutations which can confer various types of resistant acetylcholinesterases. Genetic approaches must be exploited to clarify this situation, including the cloning and analysis of genes for resistant acetylcholinesterases from which the critical amino acid substitutions can be discerned. To date, this gene has been cloned and sequenced from one insect, Drosophila, which was found to possess the identical active site sequence found in human, horse, and Torpedo cholinesterases ( 571-... 

CHRONIC HEALTH RISKS may cause skin sensitization with irritation, redness, and cholinesterase inhibition may cause mutations (genetic changes) in living cells may possibly cause reproductive damage in humans may be a teratogen in humans damages the male reproductive system decreases sperm count in animals may cause a skin allergy. 

CHRONIC HEALTH RISKS repeated or prolonged contact may cause allergic sensitization of skin an organic phosphate cholinesterase inhibitor cumulative effect of acute haz-ards/symptoms is possible may possibly cause reproductive effects in humans human mutation data has been reported. 

McGuire, M. C., Nogucira. C. P., Bartels, C. F, Lightstonc, H.. Hajra. A., and Van der Spek. A. F. L. (1989). Identification of the. structural mutation responsible for the dibucainc-resislant (atypical) variant fonn of human scrum cholinesterase. Proc. Natl. Acad.. Sci. USA 86,9.53-957. 

IV, IP, inh., skin absorption eye and severe skin irritant human systemic effects by ing. reversible cholinesterase inhibitor use may be restricted questionable carcinogen experimental teratogen, tumorigen human mutation data TSCA listed Hazardous Decomp. Prods. Heated to decomp., emits toxic fumes of NOx Uses Insecticide Regulatory SARA reportable HAP... 

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