Enzymes ester hydrolysis

Although certain pyrethroids exhibit striking neurotoxicity in laboratory animals whenadminista edby intravenous injection, and some are toxic by the oral route, systemic toxicity by inhalation and dermal absorption is low. There have been very few systemic poisonings of humans by pyrethroids. Although limited absorption may account for the low toxicity of some pyrethroids, rapid biodegradation by mammalian Uver enzymes (ester hydrolysis and oxidation) is probably the major factor responsible. Most pyrethroid metabolites are promptly excreted, at least in part, by the kidney. 

B19. Bergmann, F., Fine structure of the active surface of cholinesterases and the mechanism of enzymic ester hydrolysis. Disc Faraday Soc. No. 20, 126-134 (1955). 

Hydrolysis of esters and amides by enzymes that form acyl enzyme intermediates is similar in mechanism but different in rate-limiting steps. Whereas formation of the acyl enzyme intermediate is a rate-limiting step for amide hydrolysis, it is the deacylation step that determines the rate of ester hydrolysis. This difference allows elimination of the undesirable amidase activity that is responsible for secondary hydrolysis without affecting the rate of synthesis. Addition of an appropriate cosolvent such as acetonitrile, DMF, or dioxane can selectively eliminate undesirable amidase activity (128). 

The cyclic phosphonate ester analog of the cyclic transition state. Antibodies raised against this phosphonate ester act as enzymes they are catalysts that markedly accelerate the rate of ester hydrolysis. 

Ester hydrolysis is common in biological chemistry, particularly in the digestion of dietary fats and oils. We ll save a complete discussion of the mechanistic details of fat hydrolysis until Section 29.2 but will note for now that the reaction is catalyzed by various lipase enzymes and involves two sequential nucleophilic acyl substitution reactions. The first is a trcinsesterificatiori reaction in which an alcohol gioup on the lipase adds to an ester linkage in the tat molecule to give a tetrahedral intermediate that expels alcohol and forms an acyl... 

Enzyme-mediated hydrolysis of some racemic co-arenesulfinylalkanoic methyl esters, ArSO(CH2) COOMe, using Corynebacterium equi has led to a kinetic resolution in which the unreacted sulfinyl esters are enriched in one enantiomer at the sulfoxide center49. The enantiomeric purity of unreacted sulfinyl acetates and propionate ranges from 90 to 97%. 

Ivie 1980) and quantification of its urinary metabolites in various animal species (Bucci et al. 1992 Hart 1976 Ivie 1980 Snodgrass and Metker 1992 Weiss et al. 1994). Hydrolysis of one of the two phosphate ester bonds liberates isopropanol and converts diisopropyl methylphosphonate to IMPA. The locations of the enzymes capable of catalyzing diisopropyl methylphosphonate phosphate ester hydrolysis have not been identified. 

Fungal cutinase catalyzes hydrolysis of model substrates and in particular p-nitrophenyl esters of short chain fatty acids, providing a convenient spectro-photometric assay for this enzyme activity [101,102,116]. Hydrolysis of model esters by this cutinase showed the high degree of preference of this enzyme for primary alcohol ester hydrolysis. Wax esters and methyl esters of fatty acids were hydrolyzed at low rates. Alkane-2-ol esters were hydrolyzed much more slowly than wax esters and esters of mid-chain secondary alcohols were not... 

The study of both carbonyl and carbon acid participation in ester hydrolysis has been used by Bowden and Last (1971) to evaluate certain of the factors suggested for important roles in enzymic catalysis. A first model concerns a comparison of the three formyl esters and shows that the proximity of the formyl to the ester group and internal strain increase in passing along the series, 1,2-benzoate, 1,8-naphthoate and 4,5-phenanthroate. The very large rate enhancements result from the proximity of the internal nucleophile once formed and from internal strain. Strain is increased or induced by the primary... 

Enzyme membrane reactor for production of diltiazem intermediate. A solution of the racemic ester in organic solvent enters the port at the bottom of the reactor and flows past the strands of microporous, hollow-fiber membrane that contain an enzyme. The enzyme catalyzes hydrolysis of one enantiomer of the ester that undergoes decarboxylation to 4-methoxyphenylacetaldehyde (which in turn forms a water-soluble bisulfite complex that remains in the aqueous phase). The other enantiomer of the ester remains in the aqueous stream that leaves the reactor via the port at the top. Courtesy of Sepracor, Inc. 

The higher coordinating ability and Lewis acidity of Zn(H) ion in addition to the low pK of the metal-bound water molecule and the appearance of this metal ion in native phosphatases inspired a number of research groups to develop Zn(II)-containing dinuclear artificial phosphatases. In contrast, very few model compounds have been published to mimic the activity of Fe(III) ion in dinuclear centers of phosphatase enzymes. Cu(II) or lanthanide ions are not relevant to natural systems but their chemical properties in certain cases allow extraordinarily high acceleration of phosphate-ester hydrolysis [as much as 108 for copper(II) or 1013 for lanthanide(III) ions]. 

Enzymes are known to show high enantio-selectivity, which is a parameter one wishes to install in the MIP as well. That this is possible was demonstrated in a recent paper on enantio-selective ester hydrolysis catalyzed by MIP. The MIP imprinted with the D-enantiomer preferentially hydrolyzed the D-ester with rate enhancements of up to three comp ared to the CP [117]. Although these findings may be far from outstanding, they represent remarkable results on the route towards the generation of competitive biomimetic catalysts. 

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