Esterases properties

Pavlov, V.A., Aristova. N.V.. Moskva. V.V.. Makhaeva, G.E, Yankovskaya, V.L., and Malygin. V.V.. Synthesis of phosphorus-containing formhydi oxamoyl halides and their anticholine esterase properties, Khim. Farm. Zh.. 25. 231. 1991 Phann. Chem. J. (Engl. Transl.), 25, 255, 1991. 

Catalytic hydrolysis of ester was achieved on the snrface of nanofibers formed by the aggregation of peptide-alkyl chain amphiphiles. The esterase activity was determined using 2,4-dinitrophenylacetate (DNPA) as model substrate, and histidine residues were incorporated within the peptide backbone of the amphiphiles to mimic esterase properties. The high density of the reactive sites displayed on the surface of the self-assemblies, together with their high internal order, considerably increases the hydrolysis rate of these catalytic particles compared to catalysts in solution and in spherical aggregates, which should have less order (Figure 13)." ... 

Immobilization. The fixing property of PEIs has previously been discussed. Another appHcation of this property is enzyme immobilization (419). Enzymes can be bound by reactive compounds, eg, isothiocyanate (420) to the PEI skeleton, or immobilized on soHd supports, eg, cotton by adhesion with the aid of PEIs. In every case, fixing considerably simplifies the performance of enzyme-catalyzed reactions, thus faciHtating preparative work. This technique has been appHed to glutaraldehyde-sensitive enzymes (421), a-glucose transferase (422), and pectin lyase, pectin esterase, and endopolygalacturonase (423). 

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... 

Fluorescein absorbance is sensitive to pH. This property is utilized to measure cytosolic pH changes. Fluorescein derivatives that contain esters on the carboxyl groups have been constructed. These compounds partition through the cell membrane and, once inside the cell, the esters are cleaved by nonspecific esterases in the cytosol, leaving free carboxyl groups thus the probe cannot diffuse out of the cell (or at least does so slowly). Commonly used derivatives are 6-carboxyfluorescein (21-23) and the more recently developed probe 2, 7 -bis(2-carboxyethyl)-5(and-6)-carboxyfluorescein (13, 24,25). 

Pharmaeokinetie properties of the cephalosporins depend to a considerable extent on their ehemieal nature, e.g. the substituent R. The 3-acetoxymethyl compounds such as cephalothin, cephapirin and cephacetrile are converted in vivo by esterases to the antibaeterially less aetive 3-hydroxymethyl derivatives and are excreted partly as such. The rapid exeretion means that such cephalosporins have a short half-life in the body. Replaeement of the 3-acetoxymethyl group by a variety of groups has rendered other eephalosporins mueh less prone to esterase attack. For example, cephaloridine has an internally eompensated betaine group at position 3 (R ) and is metabolically stable. 

Some properties of the different isoforms extracted from mung bean hypocotyi cell walls (called respectively PEa, PEP and PEy, a for the neutral isoform, P for the PME with a pi around 8.5 and y for the most basic one) are reported in Table 3. The three esterases differed not only in their pi but also by their Mr, their pH optimum and the ionic strength necessary for their solubilization. 

Enzymes can be used to specifically modify the pectins. Pectin methyl esterase is already widely used to adjust the gelling properties of commercially available pectins. The acetyl esters also strongly affect the gelation [2,3] and removal is important for the upgrading of sugar beet pectin, extractable from a by-product of the sugar industry. 

The introduction of redox activity through a Co11 center in place of redox-inactive Zn11 can be revealing. Carboxypeptidase B (another Zn enzyme) and its Co-substituted derivative were oxidized by the active-site-selective m-chloroperbenzoic acid.1209 In the Co-substituted oxidized (Co111) enzyme there was a decrease in both the peptidase and the esterase activities, whereas in the zinc enzyme only the peptidase activity decreased. Oxidation of the native enzyme resulted in modification of a methionine residue instead. These studies indicate that the two metal ions impose different structural and functional properties on the active site, leading to differing reactivities of specific amino acid residues. Replacement of zinc(II) in the methyltransferase enzyme MT2-A by cobalt(II) yields an enzyme with enhanced activity, where spectroscopy also indicates coordination by two thiolates and two histidines, supported by EXAFS analysis of the zinc coordination sphere.1210... 

Some proteases show an esterase activity, especially in their catalytic activity for regioselective acylation of sugars. By utilizing this property, enzymatic synthesis of polyester containing sugar group in the backbone was demonstrated... 

M., Ito, Y., Sugiura, M., Comparative study of human intestinal and hepatic esterases as related to enzymatic properties and hydrolyzing activity for ester-type drugs, Jpn. J. Pharmacol. 

A repetition of in situ experiments with the yellowhead wrasse, partially in response to the above criticisms, again showed that fish developed a learned aversion to otherwise palatable food that had been adulterated with 15P-PGA2 [99], This was presumably due to the emetic properties of PGA2. It was pointed out that methyl esters of prostaglandins are also known to possess emetic properties [104], and reasoned that if the 15-acetoxy ester inhibits the emetic properties of PGA2, then it is likely to be quickly lost because of its known lability, especially in the presence of coral esterase. Further, the acidic environment in the stomachs of predatory fish would promote hydrolysis of these labile esters. 

The physiological significance of mucoproteins in serum is unknown but it is tempting to speculate that they may simply be intermediate stages in the synthesis of albumins and globulins. However, it will be seen below that mucoproteins with hormone properties can be isolated from serum of pregnant mares, and that the enzyme choline esterase, is probably a serum mucoprotein. 

The answer is local anesthetic properties it can block the initiation or conduction of a nerve impulse. It is biotransformed by plasma esterases to inactive products. In addition, cocaine blocks the reuptake of norepinephrine. This action produces CNS stimulant effects including euphoria, excitement, and restlessness Peripherally, cocaine produces sympathomimetic effects including tachycardia and vasoconstriction. Death from acute overdose can be from respiratory depression or cardiac failure Cocaine is an ester of benzoic acid and is closely related to the structure of atropine. 

Three isoenzymes of carboxylesterase were purified from rat liver micro-somes and were named RL1, RL2, and RH1. These differ from each other in their response to hormone treatment, inducibility, substrate specificity, and immunological properties [75], It was shown that RL1, RL2, and RH1 resemble hydrolases p/ 6.2/6.4, pI 6.0, and pI 5.6, respectively. Enzyme RL2 was found to be identical to egasyn, a protein with esterase activity found in the endoplasmic reticulum [76], The role of egasyn is to stabilize glucuronidase (EC 3.2.1.31) by noncovalent binding to the microsomal membrane. 

Some aspects of the sequence classification of esterases need clarification [87]. In the case of ES4, two separate forms were purified and found to have virtually identical specificity and chemical properties. The enzymes ES8 and ES10 appear to be a monomer and a dimer, respectively, of the same enzyme, and ES9 is probably a combination of ES7 and ES8/10 [88]. For esterase ESI5, different p/ values have been reported by different authors. 

The intracellular localization of carboxylesterases is predominantly microsomal, the esterases being localized in the endoplasmic reticulum [73] [79] [93], They are either free in the lumen or loosely bound to the inner aspect of the membrane. The carboxylesterases in liver mitochondria are essentially identical to those of the microsomal fraction. In contrast, carboxylesterases of liver lysosomes are different, their isoelectric point being in the acidic range. Carboxylesterase activity is also found in the cytosolic fraction of liver and kidney. It has been suggested that cytosolic carboxylesterases are mere contaminants of the microsomal enzymes, but there is evidence that soluble esterases do not necessarily originate from the endoplasmic reticulum [94], In guinea pig liver, a specific cytosolic esterase has been identified that is capable of hydrolyzing acetylsalicylate and that differs from the microsomal enzyme. Also, microsomal and cytosolic enzymes have different electrophoretic properties [77]. Cytosolic and microsomal esterases in rat small intestinal mucosa are clearly different enzymes, since they hydrolyze rac-oxazepam acetate with opposite enantioselectivity [95], Consequently, studies of hydrolysis in hepatocytes reflect more closely the in vivo hepatic hydrolysis than subcellular fractions, since cytosolic and microsomal esterases can act in parallel. 

Esterases play a role in regulating the platelet-activating factor (PAF), a lipid with hypotensive properties [96], Phospholipase A2 (EC 3.1.1.4) is involved in this pathway by hydrolyzing a precursor to lyso-PAF and a free fatty acid. The activity of PAF, formed by acetylation of lyso-PAF, is controlled by an esterase hydrolyzing the acetate moiety [100]. 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

---