Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various carbamic acid esters (CAE) of a new class of dopaminergic drugs, 5-substituted 8-chloro-7-hydroxy-3-methyl-2,3,4,5- tetrahydro-1 H-3-benzazepines, were synthesized and evaluated as prodrug forms with the aim of protecting the parent phenols against first-pass metabolism following oral administration. Monosubstituted CAE were found to be highly unstable at pH 7.4 and 37 degrees C, the half-lives of hydrolysis being between 4 and 40 min. Plasma from various species catalyzed the hydrolysis of the carbamates. N,N-Disubstituted carbamates, on the other hand, were stable both in buffer and plasma solutions. They showed a very potent inhibition of butyrylcholinesterase (EC 3.1.1.8), but were less potent inhibitors of the specific erythrocyte acetylcholinesterase (EC 3.1.1.17). In vitro incubations of an N,N-dimethylsubstituted carbamate ester (10) with liver microsomes from mouse and rat showed an appreciable formation of the parent phenolic compound. This bioconversion is suggested to occur via an initial cytochrome P-450-catalyzed hydroxylation to give an N-hydroxymethyl derivative which spontaneously decomposes to the N-monomethylcarbamate. It is concluded that N,N-disubstituted carbamate esters may be potentially useful prodrugs for the 7-hydroxy-3-benzazepines, whereas N-monosubstituted carbamates appear to be too chemically and enzymatically labile.
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PMID:Carbamate ester prodrugs of dopaminergic compounds: synthesis, stability, and bioconversion. 168 64

An amperometric flow-injection choline biosensor was assembled utilizing natural chitinous membrane as the supporting material for biocatalyst immobilization, and the membrane was purified from Taiwanese soldier crab, Mictyris brevidactylus. The chitinous membrane (<50.0 microm in thickness) was covalently immobilized with choline oxidase (EC 3.1.1.17 from Alcaligenes sp.) and then attached onto the platinum electrode of an amperometric flow cell. The flow cell served as the choline sensing device of the proposed FIA system. The sensor signal (peak height of the FIAgram) was linearly related to choline concentration (r=0.999 for choline up to 5.0mM) with low detection limit (S/N>3 for 10.0 microM choline) and high reproducibility (CV<3% for 1.0mM choline, n=7). The system was proved to be useful in measuring cholinesterase inhibitory activities of synthetic chemicals or natural products.
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PMID:Choline biosensor constructed with chitinous membrane from soldier crab and its application in measuring cholinesterase inhibitory activities. 1732 59

Organophosphorus compounds are extensively used worldwide as pesticides which cause great hazards to human health. Nerve agents, a subcategory of the organophosphorus compounds, have been produced and used during wars, and they have also been used in terrorist activities. These compounds possess physiological threats by interacting and inhibiting acetylcholinesterase enzyme which leads to the cholinergic crisis. After a general introduction, this review elucidates the mechanisms underlying cholinergic and noncholinergic effects of organophosphorus compounds. The conceivable treatment strategies for organophosphate poisoning are different types of bioscavengers which include stoichiometric, catalytic, and pseudocatalytic. The current research on the promising treatments specifically the catalytic bioscavengers including several wild-type organophosphate hydrolases such as paraoxonase and phosphotriesterase, phosphotriesterase-like lactonase, methyl parathion hydrolase, organophosphate acid anhydrolase, diisopropyl fluorophosphatase, human triphosphate nucleotidohydrolase, and senescence marker protein has been widely discussed. Organophosphorus compounds are reported to be the nonphysiological substrate for many mammalian organophosphate hydrolysing enzymes; therefore, the efficiency of these enzymes toward these compounds is inadequate. Hence, studies have been conducted to create mutants with an enhanced rate of hydrolysis and high specificity. Several mutants have been created by applying directed molecular evolution and/or targeted mutagenesis, and catalytic efficiency has been characterized. Generally, organophosphorus compounds are chiral in nature. The development of mutant enzymes for providing superior stereoselective degradation of toxic organophosphorus compounds has also been widely accounted for in this review. Existing enzymes have shown limited efficiency; hence, more effective treatment strategies have also been critically analyzed.
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PMID:Organophosphorus Nerve Agents: Types, Toxicity, and Treatments. 3302 36