Rate Of Ester Hydrolysis Research Articles

Cholate-independent retinyl ester hydrolysis. Stimulation by Apo-cellular retinol-binding protein.

Apo-cellular retinol-binding protein (apoCRBP) activated the hydrolysis of endogenous retinyl esters in rat liver microsomes by a cholate independent retinyl ester hydrolase. A Michaelis-Menten relationship was observed between the apoCRBP concentration and the rate of retinol formation, with half-maximum stimulation at 2.6 +/- 0.6 microM (mean +/- S.D., n = 5). Two other retinol-binding proteins, bovine serum albumin and beta-lactoglobulin, acceptors for the rapid and spontaneous hydration of retinol from membranes, had no effect up to 90 microM. These data suggest activation of the hydrolase by apoCRBP directly, rather than by facilitating removal of retinol from membranes. The hydrolase responding was the cholate-independent/cholate-inhibited retinyl ester hydrolase as shown by: 60% inhibition of the apoCRBP effect by 3 mM cholate; apoCRBP enhancement of retinyl ester hydrolysis in liver microsomes that had no detectable cholate-enhanced activity; inhibition of cholate-dependent, but not apoCRBP-stimulated retinyl ester hydrolysis by rabbit anti-rat cholesteryl esterase. Compared to the rate (mean +/- S.D. of [n] different preparations) supported by 5 microM apoCRBP in liver microsomes of 6.7 +/- 3.7 pmol/min/mg protein [10], microsomes from rat lung, kidney, and testes had endogenous retinyl ester hydrolysis rates of 1.8 +/- 0.3 [5], 0.5 +/- 0.2 [3], and 0.3 +/- 0.2 [5] pmol/min/mg protein, respectively. N-Ethylmaleimide and N-tosyl-L-phenylalanine chloromethyl ketone were potent inhibitors of apoCRBP-stimulated hydrolysis with IC50 values of 0.25 and 0.15 mM, respectively, but phenylmethylsulfonyl fluoride and diisopropyl-fluorophosphate were less effective with IC50 values of 1 mM, indicating the importance of imidazole and sulfhydryl groups to the activity. These data provide evidence of a physiological role for the cholate-independent hydrolase in retinoid metabolism and suggest that apoCRBP is a signal for retinyl ester mobilization.

Design, synthesis, and pharmacological evaluation of ultrashort- to long-acting opioid analgesics

In an effort to discover a potent ultrashort-acting mu opioid analgetic that is capable of metabolizing to an inactive species independent of hepatic function, several classes of 4-anilidopiperidine analgetics were synthesized and evaluated. One series of compounds displayed potent mu opioid agonist activity with a high degree of analgesic efficacy and an ultrashort to long duration of action. These analgetics, 4-(methoxycarbonyl)-4-[(1-oxopropyl)phenylamino]-1-piperidinepropanoi c acid alkyl esters, were evaluated in vitro in the guinea pig ileum for mu opioid activity, in vivo in the rat tail withdrawal assay for analgesic efficacy and duration of action, and in vitro in human whole blood for their ability to be metabolized in blood. Compounds in this series were all shown to be potent mu agonists in vitro, but depending upon the alkyl ester substitution the potency and duration of action in vivo varied substantially. The discrepancies between the in vitro and in vivo activities and variations in duration of action are probably due to different rates of ester hydrolysis by blood esterase(s). The SAR with respect to analgesic activity and duration of action as a function of the various esters synthesized is discussed. It was also demonstrated that the duration of action for the ultrashort-acting analgetic, 8, does not change upon prolonged infusion or administration of multiple bolus injections.

CAMP stimulates cholesteryl ester clearance to high density lipoproteins in J7774 macrophages.

The regulation by cAMP of cholesteryl ester hydrolysis and net depletion of cellular cholesteryl ester (cholesteryl ester clearance) in J774 murine macrophages was explored. Using Sandoz 58035 to selectively inhibit acyl CoA:cholesterol acyltransferase, we showed that the absolute rate of cholesteryl ester hydrolysis was stimulated 2-fold in J774 cells by the cAMP analogues 8-(4-chlorophenylthio)adenosine 3':5'-cyclic monophosphate and dibutyryl-cAMP. The rate of hydrolysis was also stimulated by prostaglandin E1, by cholera toxin, and by a mixture of forskolin and isobutylmethylxanthine, but was not affected by epinephrine or dibutyryl-cGMP. These data demonstrate that cholesteryl ester hydrolysis in J774 cells can be stimulated by cAMP-dependent protein kinase. Cholesteryl ester clearance from J774 cells was achieved upon incubation with high density lipoproteins (HDL) plus CPT-cAMP but not with HDL alone. HDL-mediated cholesteryl ester clearance was dependent on the concentration of both HDL and CPT-cAMP. The data suggest that the defect responsible for the lack of HDL-mediated cholesteryl ester clearance in J774 cells involves a failure to modulate cAMP levels.

Hydrolysis of gibberellin 7-methyl esters: anchimeric assistance by a 15-alcohol

The neighbouring group effects of 15α- and 15β-hydroxy groups on the rates of hydrolysis of gibberellin 7-methyl esters are described. The presence of a 15-alcohol increases the rate of ester hydrolysis and a 15α- has a greater influence than a 15β-alcohol. The 15α-alcohol may be effective either through hydrogen bonding between the hydroxy proton and the ester carbonyl thus stabilising the tetrahedral intermediate formed on hydrolysis of the ester, or via 7,15α-lactonisation followed by hydrolysis of the lactone. The 15β-hydroxy may act through hydrogen bonding of a water molecule between the proton of the 15β-alcohol and the 7-carbonyl function. The effect is enhanced by the presence of a 13-acetate.

Ester hydrolysis rate constant prediction from infrared interferograms

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEster hydrolysis rate constant prediction from infrared interferogramsTimothy W. ColletteCite this: Environ. Sci. Technol. 1990, 24, 11, 1671–1676Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://doi.org/10.1021/es00081a007RIGHTS & PERMISSIONSArticle Views425Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (758 KB) Get e-Alerts Get e-Alerts

Endocytosed beta-VLDL and LDL are delivered to different intracellular vesicles in mouse peritoneal macrophages.

Hypercholesterolemic rabbit beta-VLDL and human LDL are both internalized by mouse peritoneal macrophages by receptor-mediated endocytosis. However, only beta-VLDL (which binds to the cells with a much higher affinity than LDL) markedly stimulates acyl-CoA/cholesterol acyl transferase (ACAT) and induces foam cell formation in these cells. As an initial step to test whether the two lipoproteins might be targeted to different organelles (which might differ in their ability to deliver cholesterol to microsomal ACAT), we studied the endocytic pathways of beta-VLDL and LDL. Lipoproteins were labeled with the non-transferable fluorescent label, DiI. When the macrophages were incubated with DiI-LDL for 10 min at 37 degrees C, the fluorescence was concentrated near the center of the cell both in heavily labeled vesicles and in a diffuse pattern. The pattern with DiI-beta-VLDL was quite different: an array of bright vesicles throughout the cytoplasm was the predominant feature. Differences in distribution were seen as early as 2 min of incubation and persisted throughout a 10-min chase period. By using a procedure in which photobleaching of DiI fluorescence converts diaminobenzidine into an electron-dense marker, we were able to identify at the ultrastructural level vesicles containing electron-dense material in cells incubated with DiI-beta-VLDL. Human E2/E2 beta-VLDL (from a patient with familial dysbetalipoproteinemia), which has a binding affinity and ACAT-stimulatory potential similar to LDL, gave a pattern of fluorescence virtually identical to LDL. Pulse-chase studies with 125I-labeled and [3H]cholesteryl ester-labeled lipoproteins disclosed that both protein degradation and cholesteryl ester hydrolysis were markedly retarded in beta-VLDL compared with LDL. Thus, in mouse peritoneal macrophages, endocytosed beta-VLDL appears in a distinct set of widely-distributed vesicles not seen with LDL (or with E2-beta-VLDL) and, compared with LDL, has a markedly diminished rate of protein degradation and cholesteryl ester hydrolysis. The differential routing of LDL and beta-VLDL may provide a mechanism for differences in ACAT-stimulatory potential between the two lipoproteins.

Differences in the processing of chylomicron remnants and beta-VLDL by macrophages.

To gain a detailed understanding of those factors that govern the processing of dietary-derived lipoprotein remnants by macrophages we examined the uptake and degradation of rat triacylglycerol-rich chylomicron remnants and rat cholesterol-rich beta-very low density lipoprotein (beta-VLDL) by J774 cells and primary cultures of mouse peritoneal macrophages. The level of cell associated 125I-labeled beta-VLDL and 125I-labeled chylomicron remnants reached a similar equilibrium level within 2 h of incubation at 37 degrees C. However, the degradation of 125I-labeled beta-VLDL was two to three times greater than the degradation of 125I-labeled chylomicron remnants at each time point examined, with rates of degradation of 161.0 +/- 36.0 and 60.1 +/- 6.6 ng degraded/h per mg cell protein, respectively. At similar extracellular concentrations of protein or cholesterol, the relative rate of cholesteryl ester hydrolysis from [3H]cholesteryl oleate/cholesteryl [14C]oleate-labeled chylomicron remnants was one-third to one-half that of similarly labeled beta-VLDL. The reduction in the relative rate of chylomicron remnant degradation by macrophages occurred in the absence of chylomicron remnant-induced alterations in low density lipoprotein (LDL) receptor recycling or in retroendocytosis of either 125I-labeled lipoprotein. The rate of internalization of 125I-labeled beta-VLDL by J774 cells was greater than that of 125I-labeled chylomicron remnants, with initial rates of internalization of 0.21 ng/min per mg cell protein for 125I-labeled chylomicron remnants and 0.39 ng/min per mg cell protein for 125I-labeled beta-VLDL. The degradation of 125I-labeled chylomicron remnants and 125I-labeled beta-VLDL was dependent on lysosomal enzyme activity: preincubation of macrophages with the lysosomotropic agent monensin reduced the degradation of both lipoproteins by greater than 90%. However, the pH-dependent rate of degradation of 125I-labeled chylomicron remnants by lysosomal enzymes isolated from J774 cells was 50% that of 125I-labeled beta-VLDL. The difference in degradation rates was dependent on the ratio of lipoprotein to lysosomal protein used and was greatest at ratios greater than 50. The degradation of 125I-labeled beta-VLDL by isolated lysosomes was reduced 30-40% by preincubation of beta-VLDL with 25-50 micrograms oleic acid/ml, suggesting that released free fatty acids could cause the slower degradation of chylomicron remnants. Thus, differences in the rate of uptake and degradation of remnant lipoproteins of different compositions by macrophages are determined by at least two factors: 1) differences in the rates of lipoprotein internalization and 2) differences in the rate of lysosomal degradation.

Physicochemical and pharmacokinetic parameters of seven lipophilic chlorambucil esters designed for brain penetration

This report describes the physicochemical and pharmacokinetic parameters of seven chlorambucil esters, which were compared with those of chlorambucil. These esters were designed as chlorambucil prodrugs to increase the brain penetration and concentration vs time profile of chlorambucil within the CNS for potential treatment of brain tumors. They include four aliphatic esters from one to eight carbon chains in length (chlorambucil-methyl, -propyl, -hexyl, and -octyl esters) and three aromatic esters, including the phenylmethyl, phenylethyl and prednisolone ester of chlorambucil, prednimustine. The esters were lipophilic and possessed log octanol:water partition coefficients (log P values) that ranged from 4.05 to greater than 8.0. All retained alkylating activity, which was reduced compared with that of chlorambucil. In addition, all were metabolized in vivo in the rat to yield chlorambucil alone. Measurement of the in vitro rate of ester hydrolysis of the compounds to yield chlorambucil in rat plasma demonstrated that short-chain aliphatic and aromatic chlorambucil esters were rapidly broken down to their parent compound. The plasma half-lives of the compounds increased with the increasing length and complexity of their ester chain. This may have been related to an increase in the binding of the long-chain esters to plasma proteins, protecting the ester from nonspecific plasma esterases, and to a reduced affinity of plasma esterases to these esters. Pharmacokinetic analysis of chlorambucil-hexyl, -octyl, and -prednisolone esters by HPLC demonstrated that following their intravenous administration in the rat (in doses equivalent to equimolar chlorambucil, 10 mg/kg), they yielded only low concentrations of active compounds in plasma and brain. The brain:plasma ratio of these was low and similar to that of chlorambucil, and no ester demonstrated anticancer activity superior to that obtained after the administration of equimolar chlorambucil (5 mg/kg i.v., days 1-5) against brain-sequestered Walker 256 carcinosarcoma in the rat.

Regulation of hepatic cholesterol ester hydrolase and acyl-coenzyme A:cholesterol acyltransferase in the rat.

Cholesterol exists within the hepatocyte as free cholesterol and cholesteryl ester. The proportion of intrahepatic cholesterol in the free or ester forms is governed in part by the rate of cholesteryl ester formation by acyl-coenzyme A:cholesterol acyltransferase (ACAT) and cholesteryl ester hydrolysis by neutral cholesterol ester (CE) hydrolase. In other cell types both ACAT and CE hydrolase activities are regulated in response to changes in the need for cellular free cholesterol. In rats, we performed a variety of experimental manipulations in order to vary the need for hepatic free cholesterol and to examine what effect, if any, this had on the enzymes that govern cholesteryl ester metabolism. Administration of a 20-mg bolus of lipoprotein cholesterol or a diet supplemented with 2% cholesterol resulted in an increase in microsomal cholesteryl ester content with little change in microsomal free cholesterol. This was accomplished by an increase in cholesteryl esterification as measured by ACAT but no change in CE hydrolase activity. An increased need for hepatic free cholesterol was experimentally induced by intravenous bile salt infusion or cholestyramine (3%) added to the diet. ACAT activity was decreased with both experimental manipulations compared to controls, while CE hydrolase activity did not change. Microsomal cholesteryl ester content decreased significantly with little change in microsomal free cholesterol content. Addition of exogenous liposomal cholesterol to liver microsomes from cholestyramine-fed and control rats resulted in a 784 +/- 38% increase in ACAT activity. Nevertheless, the decrease in ACAT activity with cholestyramine feeding was maintained. These studies allowed us to conclude that changes in hepatic free cholesterol needs are met in part by regulation of the rate of cholesterol esterification by ACAT without a change in the rate of cholesteryl ester hydrolysis by CE hydrolase.

Characteristics and distributions of ester groups in propylene glycol alginates

The nature of the ester groups in propylene glycol alginate (PGA) has been investigated by 13C-NMR spectroscopy and chemical saponification studies. Two types of ester, namely primary 2-hydroxyprop-1-yl and secondary 1-hydroxyprop-2-yl, were detected by 13C-NMR spectroscopy by virtue of the methyl carbon resonances. From model compound studies the two forms were shown to be due to the type of ester present and not to the type of sugar residue (β- d-mannuronic or α- l-guluronic acid) to which the ester may have been bound. Alkaline saponification studies using a variety of analytical monitoring systems, and model compounds, has shown that the two types of ester exist in an equilibrium with the more thermodynamically favourable primary ester predominating in the ratio 4:1. The nature of the sugar residues, namely β- d-mannuronic and α- l-guluronic acid, to which the esters were bound, did not have any bearing on the rate of ester hydrolysis. The rate of hydrolysis of ester groups in PGA was, however, dependent upon the nature of the ester groups present, namely primary or secondary. On the basis of the evidence presented, the thermodynamically more stable primary ester predominates in PGA, as would be expected from the preparation conditions.

Retinyl esters in the vertebrate neuroretina.

High-performance liquid chromatography (HPLC) was employed to measure retinyl esters in the vertebrate retina. Both retina and retinal pigment epithelium (RPE) from frog, chicken, and bovine eyes were studied. In comparison to the RPE, the retina possessed a significant level of 11-cis and all trans retinyl palmitate. Using a sensitive radioassay, we also detected the presence of retinyl ester hydrolase (REH) activity in homogenates prepared from both retina and RPE. The rate of retinyl ester hydrolysis in these retinas was sufficiently high to supply retinal chromophores for the metabolic renewal and for the regeneration of visual pigments. In comparison to retinyl esters in the RPE, retinyl esters in the retina are located much closer to the sites of visual pigment synthesis and regeneration. Hence it is possible that these retinyl esters play a more important role in the visual cycle than those in the RPE.

Reaktionsbeteiligung von Phosphonester-Nachbargruppen bei Amindehydrierungen / Participation of Phosphonate Neighbour Groups with Dehydrogenations of Amines

Abstract Aminomethanephosphonate. Mercury EDTA Dehydrogenation. Lactam. Formamide, Aminoalkylation Aminophosphonates 1-5 are dehydrogenated with mercury EDTA to the corresponding lactams 6-9 and surprisingly to the formamide derivative 10, The different rate of ester hydrolysis of these acylamine compounds, the steric requirements and the reaction mechanisms are dis-cussed.

Relative Toxicity and Ester Hydrolysis of Pyrethroids in the Soybean Looper and Tobacco Budworm (Lepidoptera: Noctuidae)

Toxicity and rates of ester hydrolysis of the pyrethroids fenpropathrin, fenvalerate, fluvalinate, cis - and trans -permethrin, and tralomethrin to third and last instars of the soybean looper, Pseudoplusia includens (Walker), and the tobacco bud worm, Heliothis virescens (F.), were determined. Tralomethrin was the most toxic to both stages for both species, while trans -permethrin and fenpropathrin were generally the least toxic. All pyrethroids were more toxic to third instars than to last instars for both species. In general, H. virescens larvae were less susceptible than P. includens larvae. Trans-permethrin was hydrolyzed at the greatest rate in both stadia of both insect species. Fenpropathrin was generally hydrolyzed at the lowest rate. Rates of hydrolysis were similar or less in last instars of both species compared with third instars.

Cholesteryl ester cycle in cultured hepatoma cells

The existence of a cholesteryl ester cycle in cultured Fu5AH hepatoma cells was documented and factors affecting the rate of turnover of the cholesteryl ester cycle in this cell line were explored. The influence of the physical state of the lipid inclusion in which the cholesteryl esters are stored could be addressed in this cell line because these cells can be induced to store cholesteryl esters in anisotropic (liquid-crystalline) cytoplasmic inclusions by exposure to free cholesterol-rich phospholipid dispersions or in isotropic (liquid) inclusions by addition of oleic acid to the phospholipid dispersions. To examine the relative rates of turnover of the cholesteryl ester cycle in the cells with the two types of inclusions, the fraction of cholesteryl linolenate, a cholesteryl ester present in low amounts in these inclusions, was examined after cells were exposed to medium containing linolenate. After 12 h, cells with anisotropic inclusions contained 17.5% cholesteryl linolenate and cells with isotropic inclusions contained 29.8% cholesteryl linolenate, suggesting an approximately 2-fold difference in turnover of the cholesteryl ester pool. To determine whether this difference was due to a differential rate of cholesteryl ester hydrolysis, the acyl CoA : cholesterol acyl transferase arm of the cholesteryl ester cycle was blocked using a specific inhibitor, Sandoz 58-035. In the presence of this compound, cholesteryl ester was hydrolysed twice as fast in cells with isotropic inclusions as compared to that in cells with anisotropic inclusions. The difference in rate of turnover of the cholesteryl ester cycle was shown to be related to the rate of hydrolysis of cholesteryl ester which, in turn, is related to the physical state of the stored cholesteryl ester.

Non-steroidal anti-psoriatic prodrugs. Hydrolysis and aminolysis of naphthyl esters in aqueous solution

The anti-psoriatic compound, 6-chloro-2,3-dimethoxy-1,4-naphthalene diol diacetate (lonapalene) ( 1), undergoes ester hydrolysis and oxidation to give 2,3-dimethoxy-6-chloro-1,4-naphthoquinone (3). The hydrolysis reaction of 1 obeys the equation k obs = k H +[H +] + k 0 + k HO −[HO −] where k H + , k 0 and k HO − at 25° C are 1.42 × 10 −5 M −1 · s −1, 3.68 × 10 −8 s −1 and 1.78 M −1 · s −1, respectively. Both general acid and general base catalysis of 1 were observed, as well as an aminolysis reaction with primary amines. It is concluded that naphthyl esters undergo specific base catalysis by rate-determining hydroxide ion attack on the ester group to form a tetrahedral intermediate, whereas nucleophilic catalysis by amines proceeds by rate-determining proton transfer in the tetrahedral intermediate to base. It was also demonstrated that the hydrolysis rates of 1-naphthyl esters do not change greatly by altering the substituent in the 6- and 7-positions, and that the maximum shelf-life of 1 in aqueous formulations is approximately 1 month at room temperature and pH 4.

Enzymatic protein carboxyl methylation at physiological pH: cyclic imide formation explains rapid methyl turnover.

At pH 7.4, 37 degrees C, bovine brain protein carboxyl methyltransferase transiently methylates deamidated adrenocorticotropin. The methylation occurs at the alpha-carboxyl group of an atypical beta-carboxyl-linked isoaspartyl residue (position 25). Several lines of evidence indicate that the immediate product of demethylation is an aspartyl cyclic imide involving positions 25 and 26. The evidence includes (1) the rapid rate of methyl ester hydrolysis, which is consistent with intramolecular catalysis, (2) the inability of the demethylated product to be remethylated, (3) the charge of this product, and (4) its rate of breakdown. The eventual hydrolysis of the cyclic imide produces a 30/70 mixture of peptides containing either alpha- or beta-carboxyl-linked aspartyl residues, respectively. Cyclic imide formation is nonenzymatic and can explain the unusual lability of mammalian protein methyl esters in general. These findings suggest that protein carboxyl methylation in mammalian tissues is not a simple on/off reversible modification as it apparently is in chemotactic bacteria. Carboxyl methylation may serve to activate selected protein carboxyl groups for subsequent longer lasting modifications, possibly subserving a role in protein repair, degradation, cross-linking, or some other as yet undiscovered alteration of protein structure.

Ester hydrolysis by a 2-naphthylacetyl-substituted γ-cyclodextrin

In comparison with native cyclo-octa-amylose (γ-cyclodextrin, γ-CD), a modified γ-CD (1), bearing an O-2-naphthylacetyl substituent, produced larger overall ester hydrolysis rates in water (pH 8.7). A 12- fold increase was observed for p-nitrophenyl acetate, arising from both an increased rate of intracomplex hydrolysis and stronger binding, and an 11 -fold increase for m-nitrophenyl acetate, arising from stronger binding. The results were presumed to be due to spacer effects of the appended naphthalene moiety which narrows the large γ-CD cavity. The behaviour of compound (1) was compared with that of cyclohepta-amylose (β-cyclodextrin, β-CD) bearing the same substituent.

Activity of lipase in water-in-oil microemulsions

The lipase-catalysed hydrolysis rates of several nitrophenyl alkanoate esters of varying alkyl chain length (C4–C16) have been measured both in aqueous solution and in water-in-oil (w/o) microemulsions (which are known to contain discrete droplets). Lipase retains its activity in w/o microemulsions of water, heptane and sodium bis-2-ethylhexyl sulphosuccinate (AOT); the observed rates are consistent with the intrinsic activity of the enzyme (i.e. kcat/Km) being the same as in water. However, the observed conversion rates for C4 and C6 substrates are slower in the microemulsion system because of substrate partitioning to the oil-continuous phase, which results in a reduced concentration in the aqueous pseudophase. This conclusion is reached by comparing lipase and non-enzymic-(i.e. buffer) catalysed rates in both solution media. Again for the C4 and C6 substrate, partition coefficients for the substrates in the limit of high molar ratio of H2O:AOT, as determined from the kinetic results, show good agreement with measured values in heptane + water mixtures. This suggests that lipase functions effectively in the water pseudophase of the microemulsion. Lipase in the microemulsion can also catalyse the hydrolysis of longer chain alkanoates (up to C16). It can be inferred from the kinetics that such substrates partition to the interface where the lipase must also be active. In the case of AOT microemulsions, the pH profile of enzyme activity is not significantly altered compared with bulk water. The lipase retains > 60% activity in the microemulsion after incubation at 35 °C for 6 days. In w/o microemulsions of water, heptane, chloroform and cetyltrimethylammonium bromide (CTAB), the observed hydrolysis rates are significantly reduced and the intrinsic activity is reduced by a factor of twenty as compared with the AOT system. This is thought to be caused by inhibitory binding of CTAB to the protein.

ｄｅｘａｍｅｔｈａｓｏｎｅ ２１‐ｐａｌｍｉｔａｔｅの生体各種試料による加水分解

Dexamethasone 21-palmitate (DP) is a main ingredient of Liposteroid which is an injectable anti-inflammatory preparation, in a form of fat emulsion. DP is considered to be a pro-drug. Many steroid esters used therapeutically are known to be rapidly hydrolyzed in vivo. However, the hydrolysis rate of steroid esters vary with chain length. It is, therefore, very important to know the hydrolysis rate of DP and tissue distribution of hydrolyzing enzymes in relation to its pharmacology, toxicity and metabolism in vivo. The hydrolyzing activities were found in serum, liver and macrophages of rat and also in liver and monocytes of human. The affinity of DP to the enzymes is very low and DP was found to be more slowly hydrolyzed in vitro. DP is likely to be hydrolyzed by non-specific carboxylesterases. These results suggest that DP is hydrolyzed gradually and continuously to dexamethasone and exhibits a more prolonged activity in vivo.

Acceleration of the rate of alkaline ester hydrolysis by linear amphiphilic ionenes

Acceleration of the rate of alkaline ester hydrolysis by linear amphiphilic ionenes