Enzymes groups esterases

The enzyme choline esterase has been shown to have two binding points on its protein surface for these substances—one site for the quaternary ammonium group and one for X. This enzyme catalyzes the hydrolysis of an ester at the X position. From a consideration of the structure of the (2-chloroethyl)trimethylammonium chloride derivatives which were active as plant growth substances, a similar protein-binding site in the plant has been postulated. This site would have a point of attachment for both the ammonium cation and the X constituent of the molecule. This postulated site in the plant is thus similar, but not identical, to cholinesterase, which is an enzyme not known to occur in plants. There is no direct proof for this hypothetical site in the plant. 

Both steps of the process are catalyzed by the basic form of the imidazole group of a histidine residue forming part of the active site. If the native conformation of the enzyme is disrupted by denaturation reagents such as urea, the unique seryl hydroxyl loses its characteristic reactivity in both the acylation and the deacylation process (15). This is easily understood if we realize that the reactive serine and the catalytically active histidine are extremely far from one another along the polypeptide chain, being separated by 137 amino acid residues (16) they are brought into the necessary juxtaposition only by the specific folding in the native enzyme structure. The mechanism by which the enzyme acetylcholine esterase catalyzes the hydrolysis of its substrate acetylcholine appears to be very similar (17). As we shall see, a number... 

The action of OP nerve agents on the nervous system results from their effects on enzymes, particularly esterases. The most notable of these esterases is acetylcholinesterase. The active site of acetylcholinesterase comprises a catalytic triad of serine, histidine and glutamic acid residues and other important features of the enzyme are a gorge connecting the active site to the surface of the protein and a peripheral anionic site (Bourne etal., 1995,1999 Sussman etal., 1991 Thompson and Richardson, 2004), The OPs phosphy-late1 the serine hydroxyl group in the active site of the enzyme. 

Hydrolytic enzymes such as esterases and Upases have proven particularly useful for asymmetric synthesis because of their abiUties to discriminate between enantiotopic ester and hydroxyl groups. A large number of esterases and Upases are commercially available in large quantities many are inexpensive and accept a broad range of substrates. 

Porcine liver esterase (PLE) gives excellent enantioselectivity with both dimethyl 3-methylglutarate [19013-37-7] (lb) and malonate (2b) diester. It is apparent from Table 1 that the enzyme s selectivity strongly depends on the size of the alkyl group in the 2-position. The hydrolysis of ethyl derivative (2c) gives the S-enantiomer with 75% ee whereas the hydrolysis of heptyl derivative (2d) results in the R-monoester with 90% ee. Chymotrypsin [9004-07-3] (CT) does not discriminate glutarates that have small substituents in the 3-position well. However, when hydroxyl is replaced by the much bulkier benzyl derivative (Ic), enantioselectivity improves significantly. 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

These are major disadvantage of the esterase resolution process. Since die optimum pH of die enzymic reaction is generally on the alkaline side, die esters used as substrates are non-enzymatically hydrolysed and die optical purity of die L-amino adds obtained is generally low. Also the substrate has to be protected at the amino group in most cases in order to prevent formation of diketopiperasines. The esterase method is not attractive in practice and to the best of our knowledge is not used on an industrial scale. 

Enzymes catalyzing the hydrolysis of esters are termed esterases. They belong to a larger group of enzymes termed hydrolases, which can cleave a variety of chemical bonds by hydrolytic attack. In the classification of hydrolases of the International Union of Biochemistry (lUB), the following categories are recognized ... 

FIGURE 2.11 Interaction between organophosphates and B-esterases. R, alkyl group E, enzyme. 

The primary site of action of OPs is AChE, with which they interact as suicide substrates (see also Section 10.2.2 and Chapter 2, Figure 2.9). Similar to other B-type esterases, AChE has a reactive serine residue located at its active site, and the serine hydroxyl is phosphorylated by organophosphates. Phosphorylation causes loss of AChE activity and, at best, the phosphorylated enzyme reactivates only slowly. The rate of reactivation of the phosphorylated enzyme depends on the nature of the X groups, being relatively rapid with methoxy groups (tso 1-2 h), but slower with larger... 

The same enzyme (RGAE) could be purified from A. niger, together with two other esterases a feruloyl esterase (FAE) and an acetyl esterase (PAE) specific for the removal of one type of acetyl group present in the smooth regions of sugar-beet pectin. 

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